Is your glucose metabolism driven by your personal microbiome? Recent research reveals how the microbiome influences blood glucose, weight gain and weight loss. And how the new company, “Day Two”, is using microbiome sequencing data to provide personalized nutrition recommendations.

In this episode we discuss how personal your blood glucose response and regulation is. We look at how glucose metabolism can differ from one person to another, and how it differs based on typical measures, such as the hypoglycemic index. Most research studies try to understand what a diet or food does to an average person. But the question is whether you or any of us is an average person? Will your body respond to inputs in the same way as it will for an average person?

I found out that collecting personal data for myself is more useful than following the recommendations that come out of the studies that are looking at a statistical human person, rather than a real individual person. Data which is unique and personalized is usually most helpful to act on, especially when the derived conclusions differ from the mainstream nutrition studies proposals.

In the past, we have covered several aspects related to this episode. You may find it helpful to do some background listening on previous episodes before digging into this one. These include the blood glucose metabolism episodes, Episode 43 on Continuous Glucose Measurement and Episode 26 on Biomarkers of Aging – in which we discussed blood glucose as a biomarker of aging.

On microbiome testing and its use, we have had episodes that are relevant to this one. There is Episode 9 on Quantifying the Microbiome with uBiome and Episode 37 on Health Impacts of the Microbiome with Robert Knight, a well-known researcher.

“We study many different aspects of the microbiome as it relates to our health. This is another study where we studied another very basic phenomena, the yo-yo diet. What we showed there is actually that even after you complete a diet and lose weight, your microbiome doesn’t go back to what it was.
– Eran Segal

This is a two part episode with two guests. We have Eran Segal who heads up the Segal lab, which undertakes research in computational and systems biology focusing on nutrition, genetics, microbiome and gene regulation, and their effects on health and disease. This lab has released a series of studies over the last years on microbiomes and how they may be impacting blood-glucose regulation.

These studies have been heavily featured in the mainstream press because they put into question lots of our assumptions of how diets and food work, and how they impact blood glucose. Eran Segal earned his Ph.D. from Stanford in 2004, and in 2011 he was made a professor at the Weizmann Institute of Science, which is very well-known in Israel.

“What we do is give you a mobile application. So you get a personalized mobile app that you download, and it’s tailored just for you. It gives you a microbiome report, because we did it and we have it… We’re giving you your top food and meal recommendations. You have your top breakfast, your top lunch, your top dinner, your top fast food, because even when you eat fast food once in a while, you can still choose healthier fast food than others.”
– Lihi Segal

Our second guest is Lihi Segal – same last name but, no relation. She is the CEO and Co-Founder of DayTwo, which is the new microbiome lab-testing and personalized diet and recommendation service that has licensed, and is applying the research from the Segal lab, on the microbiome. Lihi has held a series of CFO and COO positions in start-ups over the years. Previously, she was COO and CFO of Sisense Limited, a provider of business intelligence and analytic software. She holds an MBA from Northwestern University.

itunes quantified body

What You’ll Learn

  • Studying the glucose response as a quantifiable effect food has on our bodies (05:43).
  • Post-meal glucose levels represent direct tracking of response to different foods (13:00).
  • Tracking glucose spikes and quantifying the body’s post-meal blood glucose regulation (14:17).
  • The accuracy and usefulness of continuous glucose monitoring – new devices and helping research (14:55).
  • Constructing multifactorial algorithms for personalized prediction of blood glucose response (18:53).
  • Using high-resolution microbiome sequencing to detect specific strains of microbiome bacteria (20:31).
  • Compared to BMI or blood tests, the microbiome is a more significant factor in predicting glucose metabolism in a personalized way (22:55).
  • Different microbiome features contribute to the overall prediction of response (22:56).
  • The propensity to gain weight and the effects of artificial sweeteners (26:11).
  • The microbiome’s acquired ‘memory’ regulates weight gain mechanisms (26:53).
  • Relapsing weight-gain is regulated by the microbiome, including by regulating genes involved in energy expenditure (26:53).
  • The microbiome remains stable over time, such that consistent long-term diet changes are required for profound health effects (30:20).
  • Unlike micronutrients, small fibers are digested solely by gut bacteria – but consumption of either has sustained effects on glucose metabolism (33:38).
  • Artificial sweeteners currently being examined by Segal Lab (34:52).
  • What DayTwo does as a company and personalized services to expect in near future (35:20).
  • Providing actionable information for glucose management (42:00).
  • The basic data inputs for using the DayTwo service and integrating lifestyle into personalized diet feedback (43:26).
  • Instead of being a diagnostic company, DayTwo offers recommendations under a predictive model (45:52).
  • Where DayTwo microbiome testing and output to users stands out – comparison with competition companies (46:38).
  • DayTwo collaborates with the Mayo Clinic to replicate the Israeli microbiome study on US population – calibrating the algorithm for American foods (50:59).
  • DayTwo’s success story in Israel, public recognition, service available for pre-order in the US (53:15).
  • Plans for bringing DayTwo to the UK and European markets after first tackling the US market (55:24).
  • DayTwo US release is not dependent on the Mayo Clinic trial, but more data means continuous predictive algorithm improvement (57:34).
  • Reasons why numerous lab testing companies operate in Arizona (58:53).
  • Pricing of DayTwo services and a lower US pre-order price (59:42).
  • DayTwo takes a direct to consumer approach – offering customizable nutrition advice delivery for different individuals (1:01:51).

Thank Eran Segal and Lihi Segal on Twitter for this interview.
Click Here to let them know you enjoyed the show!

Prof. Eran Segal, Segal Lab

Lihi Segal, DayTwo

  • DayTwo: A microbiome lab-testing company and personalized diet recommendation service. Lehi co-founded DayTwo where she currently serves a CEO function.
  • MyNetDiary: LabTwo’s database for the American market is on this network’s nutrition database featuring 400,000 different US-based foods.

Tools & Tactics

Diet & Nutrition

We discussed the studies that reveal several tactics with respect to weight loss and weight gain, as well as optimizing blood glucose metabolism towards health impacts. Important aspects from Prof. Eran’s team’s research include:

  • Predicting Diet Response: We discussed the health effects and potential benefits of various diet types. A key takeaway is that nutrition can be personalized based on predicting post-meal blood glucose responses.
  • The Microbiome & Artificial Sweeteners: Segal Lab has tested for the effects of non-caloric artificial sweeteners (NAS) – namely saccharin, sucralose and aspartame compounds. They determined that artificial sweeteners induce glucose intolerance by altering the gut microbiome. Xylitol and stevia are chemical formulations currently being examined by Segal Lab.
  • Post-Diet Weight Regain: Eran’s team have shown that persistent microbiome alterations modulate the rate of post-dieting weight re-gain. As a general rule, a low carbohydrate diet is most beneficial for weight loss because this diet prevents post-meal blood glucose spikes. Compared to a meal which spikes blood glucose levels, low response meals are associated with more fat burning and with losing weight over time.

Tracking

Lab Tests

  • DayTwo: This test offers analysis of your blood glucose metabolism as a response to particular food types or complex meals.
    • The most novel feature is microbiome sequencing with the greatest resolution offered on the market – known as ‘shotgun sequencing’. This method covers the entire genetic content found in a stool sample.
    • Current price in the US is $299 pre-order, but will later cost $399 as a standard price for the US market. This is cheaper compared to Israel, where the price is $500. In Israel, DayTwo incorporates continuous glucose monitoring for all users, thus requiring more for the glucose monitor everyone receives.
  • uBiome: A company which offers microbiome testing services, using 16S sequencing technology for microbiome analysis. We covered the applicability of uBiome’s service in Episode 9.
    • While it is cheaper than DayTwo sequencing, 16S sequencing does not allow looking below the genus level of bacteria. 16s sequencing looks only at one small region of RNA rather than the whole sample and for this reason does not provide the same resolution or ability to differentiate between different species for lack of information. 16S sequencing is the most popular today for cost reasons.
    • Differentiating between specific species of pathogenic vs. benign E. Coli is not possible with 16S sequencing, but is a standard with shotgun sequencing (DayTwo testing).

Devices & Apps

  • DayTwo Food & Activity Logger: A mobile application providing personalized day-to-day nutrition and diet recommendations.
    • The app offers analysis of your microbiome in report format, based on the required LabTwo testing.
    • Additionally, it features your top breakfast or lunch food components, allows searching through a food database, and makes recommendations on alterations – e.g. substituting rice for pasta whenever fit for your body’s blood glucose response.
    • Over time, the impact of using this app should be improved health by consuming food with the aim to optimize your blood glucose metabolism.
  • Freestyle LibreThis device is used for continuous glucose monitoring and the obtained data is used to determine trends in glucose metabolism. The FDA approved this product for the US market in 2016.
    • Contains a glucose sensor and a reader displaying the glucose data collected by the sensor.
    • Segal Lab is switching to this device partly because it offers greater user convenience by avoiding the finger pricking technique for obtaining analysis-blood.
    • Eran claims the device is at least as accurate as the company states, possibly even more accurate.
  • Fit Bit Charge: A device from the FitBit company was used in Segal Lab research to track and integrate lifestyle (sleep, meditation, exercise) into predictive algorithms for personalized nutrition recommendations.

Biomarkers

  • Post-Meal Glucose Response: Measuring blood glucose levels for the two hours following a meal.
    • The most important measured phenomena by Segal Lab and subsequently used by LabTwo for making nutrition predictions – are glucose spikes following a meal.
    • Glucose spikes are sudden rapid increases in blood glucose concentrations as a result from particular meal types, or more broadly a result of your diet.
    • Glucose spikes are associated with disease (e.g. diabetes and types of cancer). Thus, avoiding such responses is important for optimizing blood glucose metabolism.
    • Other times we have discussed post-meal glucose response is Episode 7 on optimizing ketogenic dieting and Episode 43 on continuous glucose monitoring.
  • Hemoglobin A1C: This is the most used marker for diagnosing diabetes. Its interpretative power is derived from the connection between glucose and hemoglobin – the protein in red blood cells (RBCs) which carries oxygen. Because RBCs live approximately 3 months, Hemoglobin A1C reflects the average blood glucose levels over this period.
    • The results are reported in percent (%). Higher levels of hemoglobin A1C indicate poorer control of blood glucose levels.
    • Prediabetic states range between 5.7 – 6.4% and diabetes is diagnosed above 6.5%. Optimum HbA1c levels are likely below 5%.
    • A caveat: Depending on your diet, your RBCs can have a shorter or longer lifetime. Since HbA1C measures glucose accumulation having RBCs with a longer lifetime than average leads to higher HbA1C readings despite average blood glucose being low. For example, Damien’s blood glucose is typically under 100mg/dL at any time point even after many meals due to his ketogenic diet. His HbA1C has ranged between 5.1% and 5.3% during this time however low carb diets are assumed to lead to longer RBC lifetimes. Higher carb diets are typically assumed to have average RBC lifetime.
    • Both guests share the opinion that collecting HbA1C and other blood marker data is not useful for making nutrition predictions once you have microbiome sequencing data. This is because sequencing provides sufficient data when combined with an algorithm to predict an individual’s glucose metabolism and provide personalized nutrition recommendations.

Other People, Books & Resources

Organizations

  • DNA Genotek: A Canadian company supplying microbiome collection kits for DayTwo analysis. After extensive testing, DayTwo concluded that DNA Genotek offers the best state of the art technology requiring no freezing or timing. The end result is the ability to preserve stool sample in the Day0 condition for greatest result objectivity.
  • Mayo Clinic: LabTwo cooperates with the Mayo Clinic aimed at repeating the trial in Israel at the Weizmann Institute on an American population. The aim is to obtain more data and to optimize the predictive algorithm for blood sugar response to the US population. While the trial will last for a while, LabTwo is currently able to make precise predictions for US users and the data from the trial will be used to work on similar targeted future goals.
  • FDA: The US Food and Drug Administration has placed a diabetic label on CGM technology. Thus experimenting using CGM devices with individuals is not allowed, unless diabetes diagnosis has been previously established in the test participants. LabTwo partnered with the Mayo Clinic and have successfully designed a trial including CGM devices which was approved by the Mayo Clinic institutional review board (IRB) – essentially an internal ethics committee.

People

  • Dr. Saleyha Ahsan: She traveled to Israel to take part in the study on personalized nutrition at the Weizmann Institute. Afterward, this was covered in an episode of the BBC Two Trust me I’m a Doctor show.

Other

Full Interview Transcript

Click Here to Read Transcript

(00:05:43) [Damien Blenkinsopp]: Welcome to both Eran and Lihi Segal onto the call. Thank you both very much for joining us.

So I just wanted to jump straight into your research on the glucose response, and all of the other stuff you’ve been doing in the last couple of years really because it’s all kind of related. Why did you focus on the blood glucose topic in particular?

[Eran Segal]: That’s a really good question. When we started a few years ago, we wanted to take a science-based approach to nutrition.

We thought very hard about that problem, and what we should examine. And if you think of the most common approaches in most studies in nutrition they usually consist of some dietary intervention, and then they look at weight loss, or they look at a change in some marker of a disease. And that’s great because ultimately these are the parameters that we’d like to have an effect on.

But, the challenge we found with this approach is that it then takes weeks or months for these parameters to change. You know, a parameter that measures your diabetes level, or weight. And at the end of this, you get a single measure. It takes weeks or months to change, and that measure is affected by multiple things that happen to you during those weeks or months. Both the diet intervention that you give, but also many other factors unrelated, which can be then confounding to what you’re measuring.

So, we thought that maybe one of the reasons that it’s very hard to do nutritional research, and why many researchers are failing, is because they’re looking at this single measure effected by many things. So we didn’t want to go that way. Even if we see an effect, you’re not sure you can attribute it to the diet, and if you don’t see an effect it’s very hard to troubleshoot what went wrong.

So we thought very hard about this, and that led us to look at glucose levels. More specifically, the glucose levels after a meal, what’s called the postprandial glucose response, or post-meal glucose response.

So by that, what I mean is what your blood glucose levels look like in the two hours after you eat a meal, which we can also quantify using the area under the glucose curve into a single measure representing the response that you had to that meal.

[Damien Blenkinsopp]: Right, so that’s like the total area under the curve is the total amount of glucose that was in your bloodstream during that area of time.

[Eran Segal]: Yeah, you can think of that as an approximation. I’ll tell you in a moment what we really are hoping that this is actually measuring, but that’s quantifiable into a single measure. But now we have to think about three aspects, or three features of this that really led us to conclude that this is what we want to follow.

So in a nutshell, what they are is that we were convinced by all the existing literature that this post-meal glucose response is really key to weight management. It’s really key to disease – diabetes, but not only diabetes, I’ll talk about those.

Finally, and not least importantly, that it’s very easy to measure and it’s something that, not within weeks or months but within a week, we can obtain not one, but even 50 quantitative measures of healthy nutrition in a single individual.

So first, why is it important for weight loss and weight management? This is very basic, and there’s been a lot of literature on this.

When we eat – and I’m talking about healthy people, even people who are glucose intolerant, but let’s say not insulin dependent Type I diabetics. When we eat, our body digests carbohydrates in the meal and releases them into the bloodstream.

After that, there is a response of the body by secretion of insulin, whose job is to lower the glucose levels. But in addition, what insulin signals, also, is it signals the cells to uptake the sugar that’s floating around in our blood.

And then excess sugar is converted into fat for storage because it initially is converted into storage of glycogen, but our stores of glycogen are highly limited. So very fast the remainder will be stored as fat. And this is actually known as one of the primary mechanisms by which we gain weight. In other words, this action of insulin.

So, in a sense, we would have liked to even measure directly at a continuous rate insulin, but that’s technically not possible. But in healthy people – and there’s been lots of research – by measuring glucose levels you’re actually looking at a proxy for a measurement of insulin.

And there’s been work showing, for example, that if you eat a meal that spikes your glucose levels compared to a meal that does not, then after a meal that does not you have more oxidation of fat, more burning of fat.

So the connection to weight loss is very well established. There’s also a lot of literature looking at very low-carb diets, which I think as a dietary regiment it’s incompatible with life for most people. But if you look at some of the studies when you eat a low-carb diet your glucose levels are low, and in general, those have the most beneficial effect on weight loss.

So that’s item number one why we focused on blood glucose levels because it’s very important for weight loss and management. The second is disease, and the most obvious is, of course, diabetes.

In fact, diabetes is diagnosed and defined by glucose levels. It’s defined in two or three different measures; either by the hemoglobin A1C, which measures your average glucose over a period of three months or by the glucose levels that you have two hours after you eat a meal. So something very similar to what we’re measuring.

And so, of course, you directly are playing with and improving the measures by which you diagnose diabetes. By that we can manage better the disease; manage it better in pre-diabetics, even possibly reverse it in this population. And, of course, for all the people with normal glycemic levels, we can prevent or delay the onset of diabetes.

So that’s one area where it’s important, but then separate from diabetes there’s been a lot of links to cardiovascular disease, to cancer. So in cancer, this is known as the Warburg effect. We know this for 90 years that cancer cells have a very different metabolism that much more heavily relies on glucose.

And so the thought is that by limiting the amount of glucose that you provide, you deferentially affect the growth of cancer cells compared to normal cells. And there’s been associations in the literature between blood glucose levels and cancer.

There are also been associations to overall mortality. There’s one paper that tracked over 2000 people for 30 years showing that if you responded more highly to a glucose challenge 30 years ago, you’ll live longer, basically. So there’s been links to many diseases, and so we’re very confident that it also has a strong association to disease.

And the final point is what I made before that because of the technologies with continuous glucose monitors we can now really in a single week measure 50 quantitative measures of healthy nutrition. And they’re quantitative of health nutrition because of the two points I made before.

[Damien Blenkinsopp]: So you felt that it was basically the continuous glucose monitor was a game changer because you’d be able to gather a lot more data quickly, and eliminate somebody’s potential variables coming in from the longer term studies which you can avoid.

[Eran Segal]: Absolutely. So if you think about it, we actually focused on examining the direct effect, one of the ways by which food directly affects you, and this is your glucose levels.

And from everything I mentioned before, we also believed that this is really a very critical clinical marker for weight loss and disease.

(00:13:30) [Damien Blenkinsopp]: Right. Okay, great. So you focused on the post glucose response to meals specifically, but you did mention Hemoglobin A1C. Is that something else you tracked and you found useful in these studies?

[Eran Segal]: So that’s something that we measured. We found it useful for predicting how different people respond to different foods, but it’s nothing something that you measure as a direct effect of a meal.

It’s one of those single parameters that takes many weeks to change that, again, would be very hard to develop a dietary regiment that would affect that directly because of all the confounders that I mentioned before.

So in fact, glucose levels is, as far as we know, the only reliable quantitative measure that is really super relevant that we could track, and that’s why we focused on it.

(00:14:17) [Damien Blenkinsopp]: Right. And you mentioned the area under the curve is the part that you’re interested in. So I’m guessing that you’re looking at a benchmark to what’s okay, and what goes too high in terms of that area.

You said to me when I tried to give an analogy to explain that to the audience that it wasn’t quite right. How would you explain the utility of that?

[Eran Segal]: We can just say that it’s basically looking at your glucose response and it’s quantifying how much you had spikes for glucose levels after the meal. And these spikes, as I mentioned before, is what is strongly linked to everything else.

(00:14:53) [Damien Blenkinsopp]: Right. Thank you very much. How did you find the continuous monitoring technology? Did you use a specific device, and how sensitive or accurate did you find it? There’s various monitors out.

We’ve spoken about these before, and I know people that have been using them for diabetes management and so on. So I’m just interested in your opinion on where that technology is right now, if research can be improved maybe later as it advances, or is it already as good as it’s going to get.

[Eran Segal]: So I think it was very good for our purposes. Not without problems, but I think even finger pricking is problematic, and can be variable. But, there’s also progress.

There’s a recent device by Abbot that we are now shifting to using because it’s more convenient, mainly. It’s probably as accurate, possibly even with higher accuracy – that’s what the company claims. But it’s just much more convenient, and it doesn’t require the finger pricking anymore.

But overall, they definitely capture the trends. I will say that when we measure responses to 50,000 meals you really have a very large data set, and you can afford to have some inaccuracies here and there, which all the technologies have. And still you correct for that in the algorithms.

(00:16:10) [Damien Blenkinsopp]: Great, thank you for that. Moving on a bit to what you discovered is actually driving these blood sugar regulation changes. What are the examples of the most unexpected things that you saw in the data?

[Eran Segal]: Are you talking about the factors that affect it, or even just before the surprising responses that people had?

[Damien Blenkinsopp]: I’m interested in both. If we start with what you saw that maybe you weren’t expecting, and then what you think drove that, or what you discovered drove that.

[Eran Segal]: So the first key result of the study was – and this was initially very surprising – we saw that when you give different people the exact same meal, they have very, very different responses. And this is in contrast if you eat the same meal on two different days, which is what we’ve tested on an unprecedented scale of 1000 people. This is 7000 different meals standardized that we provided.

When you eat the same meal on two different days your response is going to be very similar, but when you and I will eat the same food, our responses will be dramatically different. You can eat bread and have zero response, and I can eat bread and have a higher response than what I would have if I even ate pure sugar. So it was really all over the place.

And this was even before talking about our solution, this was very surprising. And we realized also that it has a lot of implications.

Because if we realize, again, the importance of blood glucose levels to our health and weight, then what it directly means is that general dietary recommendations are always, no matter what they are, going to have limited utility. Because for any single food that we tested, we had people who had a high response and others that had a low response.

So you can’t really make a general recommendation about food. Now there are trends. There are foods that lower glucose levels on average, for some people. And that is known; it’s what’s called the glycemic index.

I think you even touched upon that in your questions. And we also saw that in the data. So whatever foods have been reported with lower glycemic index on average they have lower responses also in our data. But if you look at all those numbers that go into making that average, they’re all over the place.

[Damien Blenkinsopp]: So there isn’t a cluster around the mean, it’s widespread.

[Eran Segal]: Exactly. It’s very spread across it. And when you measure enough people the means will be significantly different, but there is a wide spread across the means.

Meaning that we can take ice cream, for example, which on average induced relatively low glucose levels, and we can take rice, which on average, induced high glucose levels, but you will still find people that respond more highly to ice cream than to rice.

(00:18:49) [Damien Blenkinsopp]: So it’s quite surprising in those terms. So, in terms of what you’ve found or discovered that drove that. I know you tested for a lot of different things. What sort of things did you also test for in order to try and find the pattern of what was driving this?

[Eran Segal]: So we looked at many different things. We looked at body measures, anthropometries, height, weight, waist for instance and so on. We looked at several metabolic parameters in blood. We looked at questionnaires.

So we had a medical background in food frequency and lifestyle questionnaires. And the most novel component that we integrated into the study is the microbiome. So we measured all of those. In fact I will say that we found an association, a strong correlation, between variability and the response to food in all of these different groups of parameters that we measure.

And then the next step was to take all of these parameters and integrate them into rules, or an algorithm, that basically given your inputs to all of these factors, which vary from person to person, we would be able to predict how you would respond to each and every single food or food combination or complex meals.

And we showed that that actually works very well, and predicts personalized responses with very high accuracy. In fact, the accuracy that we think is even feasible because, even when you eat the same meal on different days, I mentioned your response is going to be very similar, but it’s not going to be identical.

So there is some inherent biological variability, and our predictive power is approaching that variability.

(00:20:30) [Damien Blenkinsopp]: Okay, great. The microbiome was the novel part of this. What exactly did you look at? Because there’s a few different approaches to looking at the microbiome right now.

What were you looking at and trying to map with it?

[Eran Segal]: So we looked at the most comprehensive in terms of resolution, which is just doing shotgun sequencing. So that’s basically sequencing the entire content of what we find in a stool sample. That mostly consists of bacteria, but this type of sequencing is really the highest resolution.

It allows us to identify individual genes in the bacterial composition, of which there are several millions in each and every one of us. It allows us to identify not just species, but also specific strains of bacteria.

And so there are many of these different factors that we integrated together, and used them in the algorithm.

[Damien Blenkinsopp]: Great. Is that cost prohibitive verses some of the other technologies that are used out there?

So you have the 16S, which is just looking at one part which some of the projects like uBiome are using right now to enable them to serve many consumers and make it a lower cost so people can afford it right now. Are the costs much higher for what you were doing?

[Eran Segal]: So first of all, for 16S, I will say that we didn’t want to go in that direction because science-wise I don’t think we would have gotten as predictive power.

And in fact we even showed that to ourselves in the study because it doesn’t have the resolution, and in many cases it doesn’t allow you to go below even the genus level of bacteria. So you can have the pathogenic E. coli or non-pathogenic E. coli will have identical 16S; you won’t know what’s in there. Just to give an example.

So we went for the shotgun sequencing. It is indeed much more expensive. If you talk to researchers they’ll tell you that it’s way more expensive.

I will say that what we have been working on in our labs for many years prior to this study, and then as part of the study, is to optimize this process very extensively using automation and using robotics.

We’ve substantially reduced the cost; it is still significantly more expensive than 16S. But I think our margins of error are much smaller than other researchers, and this is probably also why we were able to profile at that level.

(00:22:53) [Damien Blenkinsopp]: Okay, great. So, in terms of the microbiome – because we’re talking a lot about the microbiome and the other factors – is there a stronger weighting of the variability? Are there variants associated more with the microbiome, or are there some other factors that are really important?

The other thing that is interesting is the microbiome actually does change, and we’re trying to change it and improve it and so on in many clinical situations now. Whereas your height, age aren’t changeable.

So if you could give me a bit of background on what you found is the biggest weighting there, and maybe which is most actionable?

[Eran Segal]: Those are two very good questions.

Related to what is most important, every component that I mentioned before we can show has significant predictive power. Now of course, in terms of predictive power, some of these components are somewhat redundant with each other.

So for example we found that when you add the microbiome and some other components, then we can do without all of the blood tests, and in fact we don’t need them at all for the predictive power. They add really something negligible.

Of course we think that blood parameters are predictive; it’s just that in the context of many other parameters, they’re somewhat redundant because they can be explained and correlated with several other parameters. And so likewise with the microbiome we found that actually unlike blood, in every context that we apply the algorithm, the microbiome always had a significant contribution to the prediction.

I will say though, that of course the microbiome has the most significant contribution when you add it by itself. As soon as you add more and more parameters, this is expected. It’s marginal contribution. And also, I believe this is an area where with additional research we can dramatically improve in the future.

We already have started this process because we have a lot more information and a lot of smarter ways by which we can handle this data, which is not true for BMI, weight, blood parameters, which are very limited in the amount of information they have.

[Damien Blenkinsopp]: Right, because there is basically truckloads of data we’re going to be taking out of our microbiomes, because there’s so much in there.

[Eran Segal]: And when we and others continue to research and identify key genes in the microbiomes that are helping in the breakdown of certain products, production of different metabolites that affect us, and we know better how to zoom in on different features, we’ll be able to improve the predictive power from it.

(00:25:25) [Damien Blenkinsopp]: Great. So in terms of the level, you mentioned that the technology that you’re using goes right down to the strain level, and the species, and genus, and so on. But where do you see the patterns?

Is it on the genus level, the species level? Is it just one species that can completely change how we respond? Or is it at a very high level like bacteroides, or something like that?

[Eran Segal]: So there are significant associations on all levels.

And I can say that it’s not a single species that is really dominating. We actually have this in our paper; we have many different features from the microbiome each make a contribution to the overall prediction, but together there’s dozens of these features. Together they make a significant contribution.

[Damien Blenkinsopp]: Right. It’s really a multifactorial analysis.

[Eran Segal]: Yeah.

(00:26:10) [Damien Blenkinsopp]: Okay. You did a paper before 2014 on the artificial sweeteners, which also got a lot of coverage. That was interesting also.

And in that one I believe it was the high bacteroides and the lower clostridiales which showed that you had a higher propensity to gain weight, wasn’t it? Rather than just blood glucose regulation.

[Eran Segal]: Yeah. So yes, we did see an overall effect there. But also there we developed an algorithm that could predict susceptibility, in that case, to consumption of artificial sweeteners. And that was also multifactorial basically using dimensionality reduction of essentially all the species that we had in the sample.

(00:26:53) [Damien Blenkinsopp]: So the most recent paper you are looking at is also looking at regaining weight after dieting.

For example, if you go on a diet and there’s this typical yo-yo effect where someone goes on a diet and they just regain it all back. I’m wondering is that related to the microbiome or what’s going on? So if you could relate what you’ve been looking at there and what you found?

[Eran Segal]: Yeah.

So we study many different aspects of the microbiome as it relates to our health. And this is another study where we studied another very basic phenomena, the yo-yo diet that you mentioned. And what we showed there is actually that even after you complete a diet and you lose weight, your microbiome doesn’t go back to what it was.

So it’s very well known that as you gain weight your microbiome changes, and what we showed is after you lose weight your microbiome doesn’t revert back to the original state. And that memory, if you will, of the microbiome is in fact sufficient to induce and enhance weight gain once you stop the diet.

So I would say it’s another work further establishing the causal link, and providing more insights into mechanisms by which the microbiome plays a key role in our health, and specifically with respect to metabolic states and diseases; in this case relapsing obesity.

[Damien Blenkinsopp]: In that study did you find any mechanisms? Is it specific species? I think you were talking about metabolites in there as well.

[Eran Segal]: Yes. So this work was in fact work in animal models; this was work in mice. And the advantage of is that we can really go deeper into mechanisms, unlike in humans where it’s much harder.

And so there, we also did a metabolomic profiling, and we identified metabolites that were missing after you lose the weight. And when we administered these molecules back, we in fact were able to cure the mice of the phenomena of relapsing obesity.

[Damien Blenkinsopp]: Wow.

[Eran Segal]: And more important we actually showed that these metabolites in fact regulate genes in the host, in the mouse, and they regulate genes that affect energy expenditure. So these mice, when they have less of these metabolites which are broken down by bacteria, when the bacteria break them down, these mice are going to have less energy expenditure and therefore more weight gain.

[Damien Blenkinsopp]: Wow. So I guess you don’t understand why that energy expenditure is going on. There’s probably quite a complex downstream process that follows.

[Eran Segal]: Right. That’s quite complex, but we also had some insights in the paper as to that as well, and we found some genes that regulate that process in brown fat tissue that are directly affected by these molecules. And these molecules are made less available because the bacteria in mice that had a previous history of obesity, in fact, were breaking down and taking away these molecules more.

[Damien Blenkinsopp]: Wow, so it’s actually the introduction of new bacteria for the weight gainers, which is taking away these substrates.

[Eran Segal]: So in this case, it was metabolites. So there are specific metabolites that are broken down by bacteria, which we showed here, we call that post-biotics as opposed to pre-biotics.

[Damien Blenkinsopp]: Right, by adding the bacteria that’s missing or making taking away the ones that are causing the problem.

(00:30:17) [Eran Segal]: Yeah. Those can be technically more challenging in some cases, but in general yes.

I also want to relate to, you asked me before about the stability, or how much the microbiome changes. And we have several studies on that; in fact, some are not even published. What we find is in fact the microbiome is actually much more stable, perhaps, than most people think.

So in fact your microbiome, unless there is very dramatic change in health or weight, is probably going to be very stable even across many years. We have data on that. And what I mean by stable, it means you will still look more similar to yourself even after following some dietary interventions, at least in the short term, than you will to other people.

Now, having said that, we also found that short term dietary interventions in fact do change the microbiome, also in consistent ways, across different people. So while you’ll still remain in the neighborhood of what your microbiome is, still some functions will go up, some will go down. Those can be consistent across multiple people who consume the same type of dietary intervention.

[Damien Blenkinsopp]: Right.

Just as a takeaway from that, do you think the microbiome is going to be an important area of work? Basically learning how to modify it, push it in another direction in order to solve things like weight gain, blood glucose regulation. Is that your hope?

[Eran Segal]: Absolutely.

So the more we find causal effects for the microbiome on our health and weight the more this should be a target for intervention. But of course that will require further studies to understand what is casual and also how to change it.

And I do believe that with – and this has also been shown – that with long-term changes in diet, you will in fact achieve changes in the microbiome. But with short term dietary intervention the changes will be consistent, but they will be more subtle and you’ll still remain in your own neighborhood.

And what that means in terms of the research that we did, it means the algorithm is going to give you essentially the same predictions, even in a very stable fashion, across even some small, short term dietary interventions because your microbiome is essentially going to be very much the same.

[Damien Blenkinsopp]: Right. So if I test one month, and then I test six months later after doing a series of interventions – maybe not too intense, something like courses of antibiotics, things like that might be more intense.

[Eran Segal]: Antibiotics is probably a different story. That can have a dramatic effect.

I’m talking about even if you change your diet for a few months, your microbiome is not going to change a lot. If you maintain a very different diet after a prolonged period of time – I can’t give you exact numbers, but a long time – then you will see change.

And at some point, those changes may be large enough you may want to test yourself to make some modifications to the diet. But, for a very long period of time, without dramatic interventions it should stay pretty much the same.

[Damien Blenkinsopp]: It might be interesting if you do a course of antibiotics, because people have to from time to time, to redo the test and see what it predicts afterwords. Maybe some of the food responses are going to be different.

[Eran Segal]: Absolutely. And I think after antibiotics you will have very significant changes, and those could affect the prediction.

(00:33:37) [Damien Blenkinsopp]: Yeah. So the last thing, just going back to the artificial sweeteners we spoke about. Because they did see that those had an impact on the microbiome over time.

Do you think smaller things like that, basically micronutrients or small fibers, not necessarily macronutrient profiles, but those kind of things could have longer term impacts on the diet?

[Eran Segal]: Absolutely. I would say some of them could even have bigger effects than macronutrients. So fiber, for example, is something that is digested solely by our gut bacteria, so definitely could, and this is known, have alternations and will overtime have sustained effects. So yeah, absolutely.

I think the way we think about it now, and even drugs. We and others have shown that the drugs that you take actually also affect your microbiome. Any substance that you intake, although depending on the substance, might just go through your gastrointestinal track, meet the trillions of bacteria that are there.

They have 100 times more genes than we do. They could definitely break down these products, they could convert it into other products. I would think of it right now, anything that you intake could definitely affect your microbiome.

(00:34:50) [Damien Blenkinsopp]: Yeah. Alright. Thank you very much for that. Just a last few things.

A lot of people take xylitol and stevia. It wasn’t in your original study, and I was just wondering if you knew anything about that. Because the other ones, aspartame, saccharine, and there was another.

[Eran Segal]: Sucralose.

[Damien Blenkinsopp]: Sucralose. Yeah. It was a bit of a negative view on them in terms of what they were doing to the microbiome. Have you got any information or did you see anything on the other two?

[Eran Segal]: We are studying those now.

[Damien Blenkinsopp]: Great.

Eran thank you so much for your time. It was really useful.

[Eran Segal]: Okay, great.

(00:35:19) [Damien Blenkinsopp]: Excellent. Okay, Lihi, let’s talk about DayTwo and what you’re doing there.

So basically you’re taking the work done by Eran and his co-researchers and you’ve been turning that into this algorithm service to help optimize people’s diets. Could you give me a bit of an overview, how you look at it? What the company’s doing and how you see it going forward over the next year or so?

[Lihi Segal]: Yeah, so we licensed the technology in an exclusive way about a year ago, in the summer of 2015.

And then what we’ve been doing since then with the help of both scientists, because our founders are scientists and they’re on the management team and very deeply involved in the company. And so there’s a lot of hand-holding in that sense on the scientific level as well.

But what we’ve been doing, we built a team up of machine learning experts in DayTwo and also developers, and we really dove into the algorithm.

As you heard, on the research level the first thing they took 30 metrics in the blood, they did the microbiome, both 16S and the full shotgun. What we really tried to do is once we have all the results is really look into the algorithm and see what is that minimum set of features that we need, and write it to consumer. We don’t want to send them to get anything that is redundant.

So looking into that features into the algorithm, and looking to see what we really need, how to commercialize this. So we went through a kind of learning period when we’re looking to see how we define the product, what do we need. Do we need to freeze your stool? Do we need to send you to a doctor to get blood tests, yes or no?

And where we ended up is by looking at a really minimum set; because as you heard Professor Segal say, the microbiome was very significant in any constellation that they took, and made other things redundant. So really where we ended up with on the product side is that it’s all online, almost.

So you come online and you fill in a lot of questions – not a lot, I think a 10 minute questionnaire. But, of course it has to do with your anthropometrics and your food preferences and your medical history. Any information you just fill in your questionnaire. And then we mail home a kit; just a box. In that box there is a small tube and you take a stool sample at home.

So we use DNA Genotek as our supplier of the kit. If you know them, they’re out of Canada. This is really kind of state of the art microbiome collection kit. You don’t have to freeze it, you literally just take it when you can, when it fits you. You don’t have to time it. It’s there, you take it, and then you just mail it back to us by regular mail.

[Damien Blenkinsopp]: Is it a quick swab, or are you actually taking a sample?

[Lihi Segal]: We tested a bunch of other alternatives as well, but this company really gave us the most stabilized microbiome in extreme temperatures.

It’s really important for us to stabilize it and then send it through the mail. And you don’t have to freeze it and all that. So it made it much easier on the consumer side, and it’s also very important scientifically to get the microbiome at the state it was as it was collected in Day Zero.

So we did a lot of trial specifically on that to see that what the company claims is actually right. And so we send you this kit, you mail it back to us, and then we sequence it.

We chose to sequence, as Eran said, on a full shotgun basis because we found that that resolution rate gets us the prediction into a higher level and a very good level. So we decided to do that despite the higher costs that it has.

But again, we try to put a product on the market that is very good; it’s good scientifically, we don’t really cut the corners there. So although the cost is still higher, we do expect it to go down a scale, both on the full shotgun basis and the kits.

And then what we do is give you a mobile application. So you get a personalized mobile app that you download, and it’s tailored just for you. And it gives you three things initially.

It gives you a microbiome report, because we did it and we have it. Not all our users are going to love it, but a lot of them may be curious to open it up and see. And so there’s a lot of information there.

We’re giving you your top food and meal recommendations. So what that means is that we really look into different categories. You have your top breakfast, your top lunch, your top dinner, your top fast food, because even when you eat fast food once in a while you can still choose healthier fast food than others.

We’re really trying to bring this into your day-to-day and make little changes and not turn your world upside down. And then there’s whatever alternatives with pasta, alternatives with rice. That’s really general.

And we’re really giving you your top A+ meals and scores all the way to your worst list, which has up to C-. So we’re trying to educate you through that stage. You could always go to see what your top breakfast is, what your top lunch, and all that, but then you also have the ability to search.

If we didn’t say something that you eat and you want to know what your score is, you just search for it in our database. In the US we are based on a database of MyNetDiary. So we have 400,000 different foods that are US based foods.

In Israel we are have a different database that has Israeli foods in it. So people can really find what they eat in there.

[Damien Blenkinsopp]: Right, so these are actually branded products you can buy. Is that what you’re saying?

[Lihi Segal]: Yeah, there are a lot of branded there as well, but there’s also, for example, an apple without skin.

[Damien Blenkinsopp]: Okay.

[Lihi Segal]: You also get your just general food as well, but you would find your specific brand of whatever, yogurt, that you’re eating in the specific territory. And then, so that’s the second thing. The third thing is the search and also a build your own meal kind of possibility.

So the whole point here is that we’re not scoring nutrients. We’re not saying carbs or proteins, and we’re not even going into a family of pasta versus rice. It’s very different if you eat a pasta with cream sauce or a pasta with meatballs, or you eat a pasta with macaroni and cheese.

You have to be able to score complex meals, and that is where our kind of secret sauce is, we’re really looking at your personalized response to these complex meals. And so you can just search for those meals if you want. If you’re cooking or if you’re sitting in a restaurant and you’re able to get your scores on the foods that you’re eating.

(00:42:00)[Damien Blenkinsopp]: Yeah. So just to clarify, this is just focusing on glucose management? So lowering…

[Lihi Segal]: Right. So what we aim to do is balance your blood sugar levels. So when you go on and you eat your A+ or A- foods and you eat that on a consistent basis, and you keep portion control.

So it’s not a kind of blank check to eat as much ice cream or drink as much beer as you want, unfortunately. But it does allow you some flexibility with foods that are surprising. Things you thought were unhealthy, all the sudden you understand you can eat them. And vice versa, so it’s surprising in both ways.

And then if you eat that consistently then yes, you’re going to see that we’re helping you balance your blood sugar levels.

And as Eran mentioned, balancing your blood sugar levels has an importance both in minimizing the risk for diseases of all kinds. Even as a healthy person, you don’t have diabetes but it is really important to keep your stable blood sugar levels. And also the whole thing about weight loss.

It helps you, it encourages weight loss in that sense. So you need to have a restrictive diet; you can’t eat whatever you want and think that you’re going to lose weight with this. But it does help you lose weight, it helps control your hunger, it helps control your cravings. And so it really helps you to plan and choose your foods right. That’s what we’re aiming to do.

(00:43:25) [Damien Blenkinsopp]: Okay, great. So, just to be clear. In terms of the inputs, it’s mostly filling in a questionnaire. Is there any other test apart from the microbiome sample? Or is that just the only one that they need to do?

[Lihi Segal]: No, the basic thing is that we need the microbiome and we need your questionnaire.

Now if you do have addition information, if you have your HBA1C levels then we’ll be happy to take them in. If you have more blood tests it’s always good to take in. But it’s not as significant enough so we’ll say you have to do it.

[Damien Blenkinsopp]: Yeah.

[Lihi Segal]: But on a general level, as much information as you’re willing to give us, it will always help, yes.

[Damien Blenkinsopp]: So in your algorithm, it will just take that into account as well?

[Lihi Segal]: Yes.

[Damien Blenkinsopp]: It’s just that in terms of the cost, you don’t want to add to the cost or be inconvenient.

[Lihi Segal]: Again, as Eran mentioned, it becomes redundant at some point.

And so if you have it, great, but we don’t want to get people – the cost is not that much for an HBA1C, it costs like 20 dollars in the US today. So that’s not really the issue.

It’s more just this is the basic package; you send it home, you send it back. But as we’re looking at our future products and as we interact with you throughout your day, the app is going to allow you in future versions to report to us what you ate.

And we have a lot of insight on your sleep and on your exercise. That was not published, but we have it in the data, and they haven’t published that data. He didn’t mention it, but in the research they actually had people logging in their foods, but also their sleep and also their meditations and their exercise. They had a Fitbit on everyone.

So there’s a lot of insight that we’re going to be able to give you. And when to eat your biggest meal, because people have a certain rhythm and that’s personalized as well. So when would be preferred to have a large meal of the day. In the US usually it’s dinner. In Israel sometimes it’s lunch, sometimes it’s dinner.

Certain foods that you should eat at certain times of day. So we can really interact with you over time if we have more information on how you slept last night and how much fiber you had in the past 24 hours. There’s a lot of things that go into the algorithm that, if we don’t have them, fine, but if we do it can even help us give you better results.

[Damien Blenkinsopp]: So you’re integrating these lifestyle factors as well into the computations to tell people when to eat. That’s great.

[Lihi Segal]: Your stress levels, all that.

(00:45:52) [Damien Blenkinsopp]: So I was wondering, are you able to tell the status of someone?

Say I’m glucose intolerant to an extent already, when you get the data from people without getting the HBA1C, for example, are you going to be able to know this person’s going to have to be more careful? Is any of that kind of information coming out?

[Lihi Segal]: We’re not at any point a diagnostic company, so whatever we see we will not tell you.

[Damien Blenkinsopp]: Oh, okay.

[Lihi Segal]: We don’t do health assessments on you. We’re giving you your recommendations under a predictive model.

And for example if we find things that we think you should know, then we would probably say maybe you should see your doctor, or take these results to your doctor or something like that. We would never go into actually giving you any medical advice.

(00:46:35) [Damien Blenkinsopp]: Right. The same usual thing. There’s a lot of blood glucose dis-regulation that goes on way before you get to diabetes, as Eran was saying.

So I’m just sort of interested from an algorithm perspective. I know you’re not going to publish it because there’s a medical borderline there that you don’t want to go near, but I was just interested from an algorithm perspective – can it tell how far you are along that line? Because everyone’s got a little intolerance. I’m just curious, does it offer any information?

[Lihi Segal]: I can’t.

[Damien Blenkinsopp]: Okay, fine.

[Lihi Segal]: I can’t answer that question.

But as Eran mentioned, we’re looking into on the road map for DayTwo that’s not just for the people who want to buy it right now but we are looking into various things we can do with the data that we have, the data we collect, and the things that we learn. And of course diagnostics and therapeutics are a part of that whole agenda.

And so there’s insight that we’re looking into and collecting, and can very well come out with additional products that are related.

[Damien Blenkinsopp]: So as a first stage it’s basically a food recommendation engine as the output, and of course your microbiome data.

Do you have an idea of what type of microbiome data is going to be given? I know we talked about uBiome, for instance, in the past. We had Rob Knight from some of the other tests.

We’ve looked at a few different ones in the past. Have you got an idea yet, or are there pictures or anything of what it’s going to look like in terms of the data you provide for the microbiome?

[Lihi Segal]: I can definitely go back and send you some information about how it’s going to look, more or less.

[Damien Blenkinsopp]: Alright, cool.

[Lihi Segal]: But we’re trying to go into a lot of detail. Again, we’re doing full shotgun so we have additional insight. We’re not at just a very high level; we are looking into specific types of bacteria and trying to link them. We’re looking at studies and just general information about them.

Again, we have to be a little bit careful and not tell you anything that you may be alarmed with, or if you think that you have this and you’re going to be Type II or anything like that. So of course we’re being careful in the way that we present it. But there’s a lot of interesting information.

We’re also looking to do this in a very cool way that’s going to be, at least on the web – on the mobile it’s going to be a little flatter – when you sign into your web, there’s a report that’s going to be very interactive. You can dive in and go all the way down to the strain level, and then come up. So it’s going to be really cool in that sense.

[Damien Blenkinsopp]: So is there going to be, basically are you going to give all of that data?

My audience tends to be on the high quantitative side, so some of them tend to be people who download the data and start playing around with it in Excel. So will you have that kind of data?

With uBiome, for example, they have two aspects of that. They have the raw data they provide for you to download, and then you can put it into software to actually interpret yourself, like biometrician software.

And then they give you graphs which are basically summarized. So there’s not all of that information there, it’s a bit different, and it’s according to their perspective. So in comparison, what will you provide?

[Lihi Segal]: No, I don’t know to tell you that we’re going to give you all of the raw data. We probably could, but we haven’t finalized that down to the core of it. But again, we have it.

We’re going to have, as I said, the report and the very interactive tool so you can explore it. And the infographics is really cool. People are just playing here with it when they’re too tired to code. So they go and start planning that. But we could also provide the raw data, for sure.

Again, I think our users as opposed to uBiome users, uBiome users are mainly people who purchased it because they were curious about the microbiome. Our users, most of them, if I need to kind of guess or what I see, the microbiome is what gets them to say, oh this is really interesting.

This is personalized for me, I have my personalized microbiome; these people are scientific based, it’s not just that somebody came up with a diet based on my blood type, there’s science here. I don’t think that a lot of them are going to be very interested in downloading the file of the microbiome and things with it.

But we could definitely allow that, or be able to do that, if we see that there’s a need for that from our users.

(00:50:58) [Damien Blenkinsopp]: Yeah, cool. Alright. I saw there was a mention of a Mayo study on your site?

[Lihi Segal]: Where did you see that mentioned, by the way? I’m trying to figure out how did that get to you. We didn’t publish…

[Damien Blenkinsopp]: Well I don’t know, I think it was just mentioned. Oh, I know where I found it.

I was looking through your FAQ and there were some directions for Mayo study people on how to find the information.

There’s a leak there.

[Lihi Segal]:L: No, it’s not a secret by far.

We are recruiting people in the Mayo clinic now, and DayTwo is all over it. We just didn’t issue the press release saying that yet. But that’s been approved and it’s on it’s way as well.

So, what we’re doing, I’m happy to share, it’s no secret. But what we’re doing with the Mayo clinic is a clinical trial that is very similar to the clinical trial that The Weizmann Institute has done in Israel.

And so we’re recruiting 500 people and going through the same process of putting exactly the same device that was used in the trial in Israel and giving them test foods that are American foods, like a bagel and cereal, and really having them log their foods and providing all that information, and a lot of blood tests. So we’re really replicating the trial.

We’re just going to do that because we wanted to make sure we’re providing relevant recommendations after we have a basic cohort of US people. It doesn’t have to be the entire 500 completed, but we just, as the Israeli one was all Israeli, with Israeli microbiome and Israeli food, we just wanted to make sure that we’re able to calibrate the algorithm and it also works on a US based population with US foods and all that.

So we’ve already kicked that off. It’s a great collaboration for us to do this with the Mayo clinic, obviously. So we’ve already connected people. If any of your users are Rochester or Minnesota based people they can go and be part of that clinical trial.

[Damien Blenkinsopp]: Right. And it will be literally a copy of the other study so they could look at the other study to see what it would entail as well.

[Lihi Segal]: Right. There’s a bit of new information there as well. So that’s the reason we’re doing that. And also to start a collaboration with the Mayo clinic for other things as well.

(00:53:14) [Damien Blenkinsopp]: Great. Do you have a timeline for that? In terms of when you might get results eventually?

[Lihi Segal]: The timeline for US, it’s opened for pre-order. I know you probably entered through the UK, so you didn’t see that, because it’s IP based.

But if you were in the US you would see a pre-order. If you were in Israel, you could also buy and start getting it. So we started selling in Israel already.

The US is open on a pre-order basis, and we’re going to start shipping kits out to people in the beginning of 2017.

[Damien Blenkinsopp]: Okay.

[Lihi Segal]: It’s just around the corner.

[Damien Blenkinsopp]: Okay. So there are people already using this service in Israel, and it’s functioning.

[Lihi Segal]: In Israel we started the whole process of getting the evaluation, the kits, out to people and getting them back and sequencing them. We’re just starting to get, we’re in the final stage of getting the application finalized, and then getting the recommendations for people.

But there are a lot of people already who are using it because they got recommendations, whether from the Weizmann Institute Study or through us.

They’re not using the fancy application with the ‘Build Your Own Meal’, but the results and all of that have been around and have been used. Actually the BBC had a great show – I don’t know if you’ve seen it.

[Damien Blenkinsopp]: No.

[Lihi Segal]: The BBC has a show called ‘Trust Me, I’m A Doctor’.

[Damien Blenkinsopp]: I don’t watch TV here, unfortunately.

[Lihi Segal]: Oh, okay. So anyway, ‘Trust Me, I’m a Doctor’, it’s a doctor that has a show and she features clinical trials. And so she actually participates in the clinical trials that she features on her show.

So after the publication itself, she approached the scientists. She came to Israel with her colleague and was profiled and went though it, got food recommendations. Then she went back home and only ate what she was supposed to eat, lost weight and felt great, her energy levels [were up].

She was all psyched about it, and featured it on the BBC in a great show. I’ll send you the links so if you want you can see them.

[Damien Blenkinsopp]: Yes, please.

[Lihi Segal]: So there’s a lot of people who are using it, but outside of the clinical trial setting as well.

[Damien Blenkinsopp]: Okay, great. So it’s already getting around.

[Lihi Segal]: It’s getting contracts. Yes, we see the results are there.

(00:55:23) [Damien Blenkinsopp]: Yeah. Okay, so in terms of just how it’s going to be available, you’re only shipping to the US. So is no one in Europe is going to be able to do this?

[Lihi Segal]: Well, soon. We get a lot of approach on our support.

After the show was aired there was like 10,000 people hitting the website. So we know that there’s a lot of people interested. And we really want to go into selling in the UK as well. We’re just trying to be [safe], being a start up and not to jump too far ahead.

[Damien Blenkinsopp]: One thing at a time.

[Lihi Segal]: Right. So we did Israel because otherwise people will kill us here if we don’t bring it home. But we didn’t even translate it into Hebrew, it sold in English.

And we’re opening in the US because it’s an important market to start in. But we have concrete plans to get into Europe in 2017. So, soon. At least in the English speaking countries.

Really, logistically it just means that we need to get this box to people, but it’s not that simple. We will need a local database of food. So there’s some work on the server side to give you your foods and the database that fits you. We don’t think we’re probably going to need a trial to do that.

So in terms of the microbiome what we see is that the changes are not that [significant]. So there’s changes in the territories in the microbiome, but they’re probably not that apart compared to where the recommendations are. So you and I are very different in the way the algorithm predicts for us.

The microbiome is different, but it’s not that different. Anyway, it works on people. It could work on the US even without the Mayo trial.

[Damien Blenkinsopp]: So it sounds like that’s a validation effort.

[Lihi Segal]: Right, exactly.

[Damien Blenkinsopp]: I haven’t looked at studies of comparison of different countries and their microbiomes. There are some?

[Lihi Segal]: There are, if you look at the [57:12 check, unclear] that they have their graph there. So these show the US and there’s overlaps between the US, Europe, and Israel.

There are differences as well, but the differences, the way it reflects it in the algorithm is not that significant. So it works.

(00:57:33) [Damien Blenkinsopp]: Do you know when the Mayo trial, how long that’s going on for?

[Lihi Segal]: Oh, the Mayo trial will take a while. But we don’t need to complete the trial before we’re able to give recommendations. So we just need to validate it in a smaller group. But we’re there collecting data.

It’s more, you know in the US you can’t put a continuous glucose monitor on people at all if you’re not diabetic. Except under IRB kind of trial setting. So on a consumer level we couldn’t find any provider that would allow us to put continuous glucose monitors on healthy human beings without prescriptions. It’s a diabetic label from the FDA.

So we don’t have the device, and in order to really collect that data in the US we need to have a clinical trial set up and get the appropriate IRB and all that. So part of the whole doing of the Mayo clinic is because we just want more data, relevant data with glucose monitors and logging of food.

So we don’t need that to continue to start operating. I don’t even want to stop it after 500, so we’re talking about opening Arizona as a site, and Florida as a site. It’s really good just for our internal research purposes to continue to get more data.

(00:58:53) [Damien Blenkinsopp]: One quick question. I’ve noticed that Arizona comes up a lot in lab testing. I’m just wondering, as you brought it up just then, is there any reason?

[Lihi Segal]: Because Mayo has a site there. So when I’m collaborating with Mayo clinic, they have additional sites other than Rochester, Minnesota. So they’re thinking of expanding this to there and I’m more than happy to get more data.

[Damien Blenkinsopp]: I was just on holiday in Arizona and I just noticed that there are a lot of lab testing companies there.

[Lihi Segal]: It’s probably due to relevant man power and cheap, and something like that.

[Damien Blenkinsopp]: I think there’s maybe some state regulations or something that make it a little bit easier. Something like that also.

[Lihi Segal]: But again, when you sell outside of Arizona then you’re going to have to comply with the state laws anyway. So I’m not sure if that’s going to help you. But I don’t really know.

(00:59:41) [Damien Blenkinsopp]: So right now for the US is it $299 for the pre-order?

[Lihi Segal]: The price is going to be $399 but we’re opening up at $299, that’s a pre-order discount. But once we stop reordering, we’re probably going to go up to $399.

In Israel it’s 500 dollars, but we’re also doing a premium product in Israel; we’re giving continuous glucose monitors to people in Israel. So we’re giving them a fancy report on their blood sugar levels and all kinds of other stuff. We can because the device that I talked about in Israel you can put it on humans that are not sick.

[Damien Blenkinsopp]: Right, wow. That sounds like quite a service. If someone would pay 1000 dollars or more…

[Lihi Segal]: No, no, 500.

[Damien Blenkinsopp]: Oh, and they’re getting that premium service with the glucose monitor?

[Lihi Segal]: Yeah. It’s a lot, 500 dollars. It’s just more expensive than the US because of the continuous glucose monitor that we’re putting on.

[Damien Blenkinsopp]: They’re quite expensive, those things.

[Lihi Segal]: Well, they cost a few hundred. I guess in the UK it’s about 80 Euros. And then the reader and then the patch cost a little bit more.

[Damien Blenkinsopp]: I looked into getting one for myself; not for medical reasons, just to play around with.

[Lihi Segal]: Abbott Freestyle. Just take the Abbott Freestyle Libre. Just look for it. Freestyle Libre and then just order it online. And I think it costs 100 Euros or something.

[Damien Blenkinsopp]: Okay. And it’s got consumables on it too.

[Lihi Segal]: And then you have a patch. You get a round patch that you put on for two weeks. It’s good for two weeks. And then you have a reader.

[Damien Blenkinsopp]: And this is the one that Eran was talking about earlier that they’ve started using.

[Lihi Segal]: Right. So you can get that online.

We bought a bunch of them online ourselves in the UK before we found it in Israel. And once we found it here in Israel we decided to go with this product that we can also collect from people their blood sugar managements and give them all the fancy reports on all that. So it’s cool.

[Damien Blenkinsopp]: Yeah, it sounds quite exciting what you’re doing in Israel, because you’ve got more flexibility there. Are you publishing anything, maybe a bit later, about that on your customer base?

[Lihi Segal]: Not yet.

[Damien Blenkinsopp]: Okay.

(1:01:51) Is there anything we haven’t covered about the service, that we’ve missed?

[Lihi Segal]: Yeah. I think that this is kind of our direct to consumer approach. So we’re selling to you directly, but what we’re really working on is partnerships. Because what we really believe is that the way you’re going to use this is also very personalized.

Some people, the fact that we give them a fancy application that’s really cool and has a report on it and teaches them what to eat and what not to eat. There’s going to be a diet planner at some point on this. So you can really be independent in the way you manage your food.

For some people that’s going to be great, but some people really need more support. So maybe they go to Weight Watchers or they use other weight management services. And once you know as a user that there’s specific recommendations for you that are personalized for you, you really can’t tolerate generalized information anymore.

I’m saying this for myself. I go to this Weight Watchers group – it’s not Weight Watchers, it’s a local Israeli group. But I can’t hear her say to me, you should eat pretzels as a snack. 100 calories of pretzels are your snack. I’ve been doing that for 15 years, and then I found that it was my number 1 spiking snack.

And I moved to a different, totally different corn-based snack that was much better for me if I’m eating that 100 calorie snack already. So I’m snacking on that.

And what we’re thinking of doing is really opening an API with a lot of services. And so you as a user can share your information with your doctor, or with your nutritionist, or with your weight management group. Or when you take out food you want to be able to get a score. You want to log in, connect to…

[Damien Blenkinsopp]: So you could plug into a meal delivery site.

[Lihi Segal]: Think of this. Let’s say you’re ordering take-out of your food. We do this every day at lunch, just because in Israel is how it works.

And so I want to log in and connect with my DayTwo account, into that service, then get a menu and my score, A, or B. I’m already in a great restaurant, I’m eating food or I’m taking it out, I want to be able to get a score and choose right.

In the US specifically there’s a lot of employer wellness programs. All of those wellness programs provide nutritional advice, but it’s generalized. I, as a user, want my personalized advice to go with me.

So, that’s kind of the partnerships that we’re doing. Some will bring us customers, some we will bring our customers to them. And we’re building a marketplace around this.

So literally, think of that that we’re not competing with anyone. That’s the strategy that we built. We want to enable anyone who wants to use this personalized service to use it in their application and services.

[Damien Blenkinsopp]: Great, to make the information more widely available.

Lihi, it sounds great. I’m sure there are insurance companies and so on who would be interested in that as well. I know they’re getting more interested in these wellness programs.

[Lihi Segal]: Of course.

[Damien Blenkinsopp]: Okay well thank you very much for your time today. I really appreciated it.

[Lihi Segal]: Sure. Thank you so much.

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What defines human microbiome health? The co-founder of American Gut Project discusses the differences we’ve found in the gut microbiome and how it influences our health. We look at tools and lifestyle choices that have been shown to change the microbiome (for good, and for bad).

Our microbiome plays an important role in our ability to overcome health issues. A healthy biome can make you resilient to these challenges, while a poorly-balanced one can create or worsen health problems. We first talked about the microbiome in Episode 9 with Jessica Richman, and today we are going to dig deeper into what affects it.

In this episode, we look at how the microbiome and our life choices impact each other. This can relate to how we live, our health, and even how many mosquito bites we get. Research shows that many chronic and gut diseases are related to our microbiome. We also talk about how medical interventions like antibiotics, Cesarean sections, and fecal transplants change our biome.

Anything that’s in the literature has got to be based on population averages. And one thing we know about people is that there are tremendous amounts of variability. So what works on average in the clinical trial is not necessarily going to be what works for you individually.
– Rob Knight

Advances in DNA sequencing have made it possible to look at the microbiomes of huge groups of people. Several large-scale projects, which we’ll discuss today, aim to look at microbiomes of groups or whole countries. It is also easier for individuals to learn about their own microbiome. This lets you see how your lifestyle, diet, or medical treatments alter your biome.

Today’s guest is Dr. Rob Knight, professor of Pediatrics and Computer Science & Engineering at the University of California San Diego. Dr. Knight was chosen as one of 50 HHMI Early Career Scientists in 2009. He is also a member of the Steering Committee of the Earth Microbiome Project, and a co-founder of the American Gut Project.

Dr. Knight and the Knight Lab at UC San Diego use state of the art computation and bioinformatics to understand the microbiome and what affects it. Dr. Knight is on the forefront of this exciting research and will walk us through the topic.

The episode highlights, biomarkers, and links to the apps, devices and labs and everything else mentioned are below. Enjoy the show and let me know what you think in the comments!

itunes quantified body

What You’ll Learn

  • What DNA and RNA are (6:52).
  • Initially researchers thought that the human microbiome would be uninteresting (8:20).
  • Advances in DNA sequencing made projects like Human Microbiome Project and American Gut possible (9:53).
  • Novel information on how lifestyle affects the microbiome (13:50).
  • The different biomes of your body, what is known about them, and how the affect the body (16:50).
  • Long-term diet has the largest impact on your gut microbiome (19:40).
  • Individuals show variation in their microbiome from day to day, and this variation could make single samples less useful (20:05).
  • Research shows that only a few activities and dietary changes significantly affect the microbiome (22:50).
  • There are still questions about how variation within an individual’s microbiome relates to health (26:08).
  • Resources like American Gut can be used to assess your own response to medical interventions like antibiotics (27:20).
  • Fecal transplants to replenish your microbiome after medical intervention is an area of promise for those battling C. difficile (28:15).
  • The effect of antibiotics on the microbiome vary among treatments and individuals (31:06).
  • The microbiome is incredibly complex, but research into a few microbes could yield tremendous health benefits (33:16).
  • Although there is anecdotal evidence that probiotics are effective at positively impacting your microbiome post-antibiotics, there are currently no clinical trials on their effectiveness (37:44).
  • The Ancestral Microbiome Project is comparing the microbiomes of people with traditional lifestyles to see if the Western lifestyle or diet has led to a loss of certain microbes (41:05).
  • Living with a group of people or a new partner can change your microbiome (42:54).
  • IBS has been linked to the microbiome, and probiotics have shown promise for treating the condition (44:20).
  • Damien and Dr. Knight discuss places to find additional information on the microbiome (45:22).
  • Dr. Knight suggests tracking travel, medications, and diet if you are interested in how your lifestyle affects your microbiome (47:11).
  • Those interested in learning more could also track their fitness, do an EEG of brain activity, or an MRI of areas of interest (49:44).

Thank Dr. Rob Knight on Twitter for this interview.
Click Here to let him know you enjoyed the show!

Dr. Rob Knight

Tools & Tactics

Interventions

  • Fecal transplant: The purpose of this treatment is to re-balance the microbiome of the transplant recipient by placing fecal matter from the donor is placed in the colon of the recipient. The most common reason for this treatment is a serious illness caused by Clostridium difficile after the healthy gut microbiome is destroyed by antibiotics.

Supplementation

  • Probiotics: Probiotics are live bacteria and yeasts that assist in gut health; this includes antibiotic-related diarrhea, IBS, and IBD. They can be found in a variety of food products (like yogurt with “live cultures”) and in capsule form. Strains of Lactobacillus and Bifidobacterium are the most commonly available.

Diet & Nutrition

  • Plant-based diet: Dietary changes can quickly alter the gut microbiome, and Dr. Knight specifically discussed the choice of animal vs plant-based diets on the rates of Prevotella and Bacteroides. Here is the paper by Gary Wu and others discussed Rob Knight. For more information, here is a paper discussing how people on animal-based diets had higher levels of microorganisms related to inflammatory bowel disease in their microbiome.

Tracking

Biomarkers

  • Microbiome community composition: To determine what is in your microbiome, labs report the percent of each type of bacteria present in your sample. We are still learning about how microbiomes affect health, so there is currently no information on what an “ideal” microbiome looks like.
  • Gut microbiome: This is the microbiome in your colon and is the most commonly assessed of the biomes. Some “good” bacteria like Akkermansia, Lactobacillus, and Faecalibacterium are associated with reduced obesity rates and gut health.
  • Fine grade fitness information: This biomarker includes daily information on caloric intake, steps taken, calories burned, sleep quantity, and sleep quality.
  • Blood and Urine Metabolites: These small molecules include amino acids, sugars, and fats. They provide insights into health, disease risks, and optimal diet. No specific biomarkers were discussed – the biomarker would be a specific metabolite. A common test is the blood metabolite panel (BMP), which looks at calcium, glucose, electrolyte, blood urea nitrogen, and creatinine levels. For urine, proteins, leukocyte esterase, and hemoglobin are all commonly assessed biomarkers.

Lab Tests, Devices and Apps

  • American Gut Project: A not for profit, research-based initiative to understand the American microbiome. Participants are asked to provide details about their diet and lifestyle.
  • Michael_Pollan_Bug_Data

  • uBiome: This test can be ordered and used by anyone in their home. The test allows collection of microbes from your gut, mouth, ears, nose, or genitals.
  • Electroencephalogram (EEG): EEGs record electrical activity in the brain. The frequency of waves can indicate whether brain function is normal or disturbed. Alpha (8-13 waves per second) and beta (more than 13 waves per second) waves are the most common in healthy, awake adults.
  • Magnetic Resonance Imaging (MRI): MRI scans are use pulses of magnetic energy to visualize internal organs and structures. It can be used on almost any area of the body and provides information on tumors, bleeding, injuries, blood vessels, or infection.

Dr. Knight’s Recommended Resources to Learn More About Microbiome

Other People, Books & Resources

People

  • Jeff Leach: Co-founder of the American Gut Project, and microbiome researcher.
  • Dr Catherine Lozupone: Professor of Biomedical Informatics andPersonalized Medicine at the University of Colorado, Denver. Dr. Lozupone researchers the impact of the gut microbiome on human health.
  • Dr. Jeffery I. Gordon: A research scientist studying the link between gut microbiota and obesity. Our guest collaborated with Dr. Gordon on this topic.
  • Dr. Pieter Dorrestein: A professor working at UC San Diego, Dr. Dorrenstein and our guest have collaborated on research. A recent paper of Dr. Dorrestein’s in PNAS looks at the chemical makeup of skin surface and relates it to the microbes that live in the skin.
  • Dr. Dan Littman: Professor of Molecular Immunology at NYU School of Medicine, Dr. Littman studies the human immune system.
  • Hans Herfarth, MD, PhD: Dr. Herfarth is a member of the UNC Multidisciplinary Center for IBD Research and Treatment and the author for the UNC Patient Guide to Inflammatory Bowel Disease (IBD).
  • Balfour Sartor, MD: Dr. Sartor is the co-chair of the UNC Multidisciplinary Center for IBD Research and Treatment.
  • Dr. Peter Turnbaugh: A professor in the UCSF department of Microbiology and Immunology.
  • Dr. Dave Relman: Dr. Relman’s research focuses on the human microbiome.
  • Dr. Cecil Lewis: Dr. Lewis studies anthropological genetics, including the evolution and ecology of the human microbiome.

Organizations

Other

Full Interview Transcript

Click Here to Read Transcript

[05:22][Damien Blenkinsopp]: Hi Rob, thank you so much for joining us on the show.

[Rob Knight]: Sure, thanks Damien, and thanks to your interest on this topic.

[Damien Blenkinsopp]: It’s great. So we’ve already looked at the microbiome, but I wanted to know, why is it that you got interested in this specific area? What is it that first caught your interest, or you first got involved in this area?

[Rob Knight]: Yeah, well it was a very indirect pathway from my graduate work at Predison’s Lab in studying the evolution of the genetic codes and a large part of that was looking at RNA molecules down to particular molecules that are useful in metabolism. So from there I went to the University of Colorado working on RNA sequence states and trying to figure out how many random RNA sequences you need to look at before you find one that does something interesting.

So there were a lot of one particular kind of sequence, the ribosomal RNA molecules in the database. I really wondered why were there so many of that particular sequence that had been studied. And so I started talking to Norm Pace, who was one of the other faculty members at Boulder. And I realized they were using the ribosome’s RNA not as an object of study in and of itself, but as a tool to understand the relationships between different organisms, and to read the mass in the communities that they were looking at. Everything from rocks to shower curtains to caves.

And so it really is just going from basic studies of RNA to understanding that you could use a particular kind of RNA as a tool to find out something about microbes, and then from there realizing that the microbial communities themselves could be used as a tool to find out about different environmental conditions, including the conditions within our own bodies.

[Damien Blenkinsopp]: Great, great, thank you.

[06:52] For some of the people at home, they might not understand what RNA is in reference to DNA, and how that works. Could you give a quick overview of what the mechanism for RNA is, and what role it plays in our bodies and the other things that you’ve been talking about.

[Rob Knight]: Sure, absolutely. So I think everyone’s familiar with the idea that DNA is the genetic material we use that passes down from one generation to the next. So, the proteins are most of the catalysts that do reactions in our bodies, most of the structural elements. So what happens is the DNA gets transcribed into RNA, ribonucleic acid, which is chemically relatively similar to DNA. And then the RNA gets translated into proteins.

But there are some kinds of RNA that don’t get translated, and have a function that is of themselves. One really important kind of RNA is ribosomal RNA that actually makes up the factory in the cell, the ribosome, that makes the proteins. And so because it plays such an important role in life, you can detect similarities in those even between very distantly related organisms.

So similarities even between us and bacteria. And so you can use that molecule to reconstruct the evolutionary tree that relates all of those organisms together, based on the similarities and differences in the sequence.

[08:04][Damien Blenkinsopp]: Great. So then you, from those studies, you started working to look at the bacteria, because you saw that they had a pretty important role, and that there was a lot of similarities between the things you were studying. On a human level and in the animal level, could you tell us a little bit about what it was that kind of pushed you to look more at the microbiome?

[Rob Knight]: Yeah, sure.

Originally the tools that I was developing together with Cathy Lozupone, then a very talented graduate student from my lab but now a faculty member of the University of Colorado Health Science in Denver. Initially we were just looking at tools to compare microbial communities out there in the environment.

So looking at the effects of things like salinity and pH as the chemical factors, of drivers, for how microbes are different in different places, like different samples of soil, sea water, or other communities like that. And so at the time we thought that maybe the microbes associated with the body wouldn’t be that interesting, because at the time there was fairly heavy bias towards the idea that most people probably have the same microbes, because if you grow them on a Petri dish, you get more or less the same thing from everybody.

But it turns out there’s a huge number of microbes in there, even in our own bodies, that we don’t yet know how to culture. And as a result, when you look at them with these culture independent, they are directly sequencing the DNA that codes these ribosomal RNA genes. And figuring out what’s in the communities directly you see all this diversity in the human microbiome that no one ever suspected was there.

So, we started doing this in mice, actually, in collaboration with Dr. Jeffery I. Gordon, he’s a physician at Washington University, a gastroenterologist. He was really interested in looking at links between microbes in obesity. So we started with mice, then moved up to humans. And then increasingly we’ve been interested in looking at the microbiome not as a static system, but as a dynamic system. So looking at how it changes over time, both in health and in disease.

[09:53][Damien Blenkinsopp]: Great, great. Thank you very much. And of course you are a co-founder of a project, which is being designed to explore the microbiome in America, of the population in America. What kind of latest update of American Gut, and what you’ve been doing there?

[Rob Knight]: Let me give you just a little back-story to that project. So, before American Gut, we were involved in the Human Microbiome Project, which was a very large scale NIH funded initiative, 173 million dollars to characterize what the microbes look like in healthy people. And with their whole microbiome, is there a lot of variation person to person, and how does it vary in different parts of the body.

So during that process, and in part because of technology that was developed, during the Human Microbiome Project DNA sequencing and tools to analyze the DNA sequences made the whole process dramatically cheaper. So essentially we wondered can we bring this technology to members of the general public, using the tools that we were able to develop during the Human Microbiome Project, to essentially allow anyone who was interested in finding out about their own microbiomes to be able to do that at a reasonable cost.

Jeff Leach and I launched as a collaboration between the Earth Microbiome Project and the Human Food Project. The crowd funded initiative where basically it’s donation supporters. And people can find out directly about swabs from their gut, and how it compares to the gut microbes of other people around America, or around the world, especially including the people who were analyzed in the Human Microbiome Project.

And also including people in Africa and South America, and soon people in Asia, to try to compare what the microbes look like, and how do they relate to health and disease.

So, unlike the Human Microbiome Project, where there were very rigorous exclusion criteria, so you could only participate if you were certified by a physician as being extremely healthy, in American Gut, we are interested in anyone, essentially to see what kinds of microbiome configurations are out there in the wild when you give everybody the opportunity to participate.

[Damien Blenkinsopp]: Great, great. That’s a great back-story.

[11:54] What’s the number of samples that you’ve collected to date? You said it’s called American Gut, but it sounds like it’s not just focused on America now, that it’s spread out and it’s available to more widely internationally. Is that correct?

[Rob Knight]: Yeah, that’s correct. So it’s relatively expensive to pass inspection internationally because the shipping regulations are fairly burdensome. So what we’ve been doing is we’ve been launching spin-offs in other countries. And so we started with Australian Gut, and with British Gut essentially because it’s a lot easier to translate all the instructions from English into English, rather than to tackle those translation issues.

But we’re hoping to expand to a lot of other countries. And at the moment with the transition from the University of Colorado to the University of California, we’re essentially in a holding path, and at the moment waiting for AMX approval. But we’re hoping to scale up the project dramatically, and greatly facilitate the ability for people all over the world to participate.

[Damien Blenkinsopp]: Which approval did you say you were waiting for? Was it an academic program approval?

[Rob Knight]: Institutional Review Board Approval. So in order to ensure that the project was conducted ethically and that the results that we get are going to be meaningful, everything we do in American Gut has been approved by Institutional Review Boards from the beginning.

I moved from the University of Colorado to the University of California right at the beginning of this year. What’s happening right at the moment is we’re waiting for the ethics approvals to be transferred from one institution to another, which can take a lot of time.

[Damien Blenkinsopp]: Right, right. Got it.

[13:19] How many samples have you collected to date for the project?

[Rob Knight]: We’ve released data from about 4500 samples. We’ve sent out about 9,000 kits. We have about another 1500 samples in hand that we’re just waiting for that ethics approval to be able to move forward on sequencing.

So, for anyone who’s listening, if you’re wondering where your results are, we’ll be able to get them out pretty soon. We just need to make sure that everything is completely compliant with all the regulations that apply to the Human Subject Research in the United States. Just to make sure that everything is completely above board.

[Damien Blenkinsopp]: Excellent. So, has any analysis come out of it, or insights yet that you’ve been able to do?

[Rob Knight]: Yeah, absolutely. So one thing that was exciting about it, or already, in the Human Microbiome Project, this paper, which came out in Nature in 2012, we looked at about 250 healthy subjects. So I think we reported data for 242 where there was information from all body sites.

So you have about 250 people involved in that project. Versus American Gut, where you have thousands of people involved. As a result, with a much larger population size we have much more statistical power to look at subtle effects.

And we also put on the questionnaire all sorts of things that were considered too crazy to ask in the HMP. But in the intervening time we’ve discovered so much more about what the microbiome does, especially in a range of different animal models. And it seemed a lot less crazy to ask those questions in 2012 than it did in 2008.

As a result, we’ve been able to see associations between the microbiome, and all kinds of things you might not have expected. So you might have expected that how old you are affects the microbiome, which it does, but you might not have expected that, for example, how much sleep you say you get a night is also linked to the microbiome. And we see a statistically significant effect of that.

Similarly, you might have expected that how much alcohol you drink affects the microbiome, but you might not have expected that we can also pick up a difference based on how much you exercise. Or I should say how much you say you exercise, because all of this is reported data. But how much you say you exercise, even whether you say you do it indoors or outdoors, has an effect.

So we’re really picking up a lot of interesting associations. And what we’re hoping to do in the next stage of the project is to take a bunch of these associations and turn them into something where we can start to get causality. So what we’d love to know, if we see in association with alcohol and an association with exercise, or with sleep or with any of these other things, is to actually encourage people to change what they’re doing in those respects, or you know more obvious things like diet, or antibiotics.

Where the idea is that if you take a sample before you have a change in any of those things, and then you have the change and then you take another sample again after. Can we start figuring out which of those changes are actually caused by those different lifestyle things that you could be doing. This is watching simply effect.

[Damien Blenkinsopp]: Right, because a lot of when we’re thinking about the microbiome, and –just to make sure I’m correct here — you’re just looking at the gut, right? The microbiome of the gut?

[Rob Knight]: Well, actually with American Gut you can look at the microbiome. So most people are looking at their gut biome, but it’s also interesting to look at other body sites. We have been sending out a number of batches of kits that allow you to sample multiple sites simultaneously.

So another project we’re doing, we’ve been looking at skin. So for example, we had a very interesting paper that came out in PNE of last week with Pieter Dorrestein doing very high resolution maps of the skin in relation to the microbes, to the metabolites. And then there’s also a lot of interest in the oral microbiome, the vaginal microbiome, and so on.

So, although the gut microbiome is where most attention has been focused, there is a lot of interest potentially in looking at other body sites. And linking them not just to health effects of that site, but also to all over the body. So for example the gut microbiome has been linked to asthma and to rheumatoid arthritis, and to cardiovascular disease, all of which takes place in sites outside the gut, but are nonetheless affected by the microbiome.

And it’s entirely possible that, for example, the oral microbiome, or the skin microbiome might also be having systemic effects we’re only just beginning to understand. Whether it’s through interactions with the immune system or through release of particular metabolites, or other mechanisms.

[17:32][Damien Blenkinsopp]: Maybe it’s too early to say this, but have you seen anything that would indicate that the microbiomes are related to each other, in terms of if you have a different gut microbiome it may influence or be influenced somehow by the fact that your nose or your skin biome is different also?

[Rob Knight]: Well that’s a very interesting and controversial question. So actually, the fifth Human Microbiome Project main papers, which said that there are statistically significant but relatively weak associations between the different body sites, and then later that’s been confirmed by other researchers using different statistical methods.

At the moment there’s a lot of debate about how strong the associations are, and what effects they have on health when you’re looking at the overall configurations. But certainly some individual organisms that are very interesting. So, for example, Dan Littman at NYU has shown some very nice work linking Prevotella in the guts to rheumatoid arthritis. And so we’ll probably see a number of other associations like that with specific organisms at one site having unlikely effects on what happens, what helps with other sites in the body.

[Damien Blenkinsopp]: Very, very interesting.

I think the surprising thing for a lot of people of what you just said is that there are a lot of lifestyle factors not related to diet. Because we normally think of the biome, and especially the gut biome, being immediately related to our diet, and what do we eat, but [not] a lot of things you mentioned, sleep, age, exercise. And you said exercise indoors or outdoors can be different as well, is that correct?

[Rob Knight]: Correct, yeah.

[Damien Blenkinsopp]: So you know, it’s very interesting. These small changes in your lifestyle, nothing to do with diet, can have significant impact on the gut also, which we haven’t looked at.

[Rob Knight]: Sure, although I should clarify that long term diet has the largest effect that we’ve seen. The work with Gary Wu and others at Penn came out in 2011 in Science. What we saw there is this long-term dietary pattern had a profound effect on the gut microbiome, especially changing the ratio of Prevotella to Bacteroides, two of the major taxa in the gut. And only changing the overall configuration, more than essentially anything else.

So the only thing we’ve seen that gives you comparable changes is either antibiotics or acute infection with some kinds of pathogens. Like C. diff, for example, has a very large effect on your gut microbial community. So long term diet is really very important.

Short term diets, unless it’s something really extreme, is a lot less important than what we see in long term diet. This was maybe consistent with people’s experiences with going on a diet for a short period, losing some weight, but then going off the diet and bouncing back again. In general your microbiome is very resilient.

[20:05]Damien Blenkinsopp]: This comes to the topic of variability of the microbiome over time.

I did see one presentation of yours where you were showing the biome of a newborn baby, actually, as it was growing up. And you’re showing the changes at that stage of its life, which were quite significant at that stage. But for adults who are fully developed, in our day to day, week to week lives, are our microbiomes changing significantly? Or are they very, very stable?

[Rob Knight]: Both of those are true. So, our microbiomes change statistically significantly one day to the next. And especially when we do things like travel or take antibiotics, or if we have a chronic, immunologically associated disease. Like, for example, inflammatory bowel disease, or rheumatoid arthritis, or other conditions where there’s a lot of variability in whether you’re in remission or whether you’re having a relapse.

There can be fairly large changes there, but typically small compared to the differences between different people. So we tend to be stable in terms of, especially if we’re healthy and there’s nothing particular going on, we tend to be stable in the sense that we’re more similar to ourselves day to day than we are to other people.

But that doesn’t mean that you can’t detect the differences one day to the next. And so a very interesting question at the moment is what is the significant of those day to day fluctuations? Might it actually be more important how much you vary than what your current state is right now. And that’s one of the things that we’re just starting to investigate at the moment.

[21:29][Damien Blenkinsopp]: Yes, and in terms of how meaningful data would be for someone who’s collecting it for themselves, if they take one sample and they get one reading is that meaningful to them? Or would you suggest they take one this week, and one next week. How would you go about making sure you have something representative?

[Rob Knight]: Right. Well having one sample is certainly a lot better than having no samples, in terms of getting some information about what’s in your gut. Because even having one sample is going to do a tremendous amount to place yourself on the microbial map, relative to other people.

The question about how frequently you should sample and how many samples you should take to get a baseline, that’s something that’s actually a very active research topic at the moment. And we have collaborations with a number of different investigators exploring that in different contexts.

So, for example, one thing we’ve been doing is work supported by the Crohn’s & Colitis Foundation of America with Hans Herfarth and Balfour Sartor of the University of North Carolina, where we’re trying to address exactly that clinical question. If you have patients with IBD should you sample daily, should you sample weekly. So how does that compare to what you should do in healthy controls.

Unfortunately, the only way we can assess that baseline data is to take very frequent samples. And it’s difficult to get people to do that. So for example, I’ve been collecting my own samples daily for over six years now. It’s relatively difficult to get people to come up to that kind of level of commitment.

[22:50][Damien Blenkinsopp]: So, I’m interested. What kind of insights have you learned about yourself from that n=1?

[Rob Knight]: As you know it’s always relatively difficult to draw conclusions from a sample size of one, but it does look like things like travel have a fairly large effect. We’ve seen that for a number of different locations.

So I should clarify that only about the first two years of that have been sequenced so far. Most of the rest are in a queue for processing, but it keeps getting bumped due to things like making sure we get the American Gut results and so on. The rest of the time series is currently pending.

We’ve done the DNA extraction so that’s currently pending sequencing. And some of the things that we’re going to be really interested to follow up on, having a time series that goes that long is, for example, the seasonality effects that we seen in American Gut. And we see those even within one individual. Because if you can repeat that for many years, then you can start to see systematic patterns.

I’ll tell you about some results from another study, which is one by Lawrence David and Eric Alm at MIT, where they sampled themselves daily for a year and collected a very large number of auxiliary variables. I think they collected over 100 variables every day, including everything they ate. All kinds of things like how much exercise they did, how much they slept, and so on.

And they found very few systematic associations. So, for example, about the only thing they saw in diet was citrus, which had a significant effect, whereas many other things that they recorded did not. And they also saw associations with travel, and associations with getting GI illnesses. And that was about it.

So, I think the issue is that a lot of the effects, although they might be important, they’re probably subtle and cumulative. And so although you’re going to get very interesting information from some of these n=1 studies, like this study. And by Larry Snar here at UCSD has been doing looking at his own gut in the context of IBD, in the context of my studies myself.

Although there’s going to be some interesting stories that come out of them, those are going to be most interesting in terms of the technology development, of asking how frequently should you sample to establish a baseline, and over what interval to you need to sample to get a decent view of dynamics.

But we did a study with Noah Fierer and Rob Dunn, Greg Caporaso that came out in Genome Biology towards the end of last year looking in healthy students at the variation of the gut microbiome over the course of the semester. One thing that was very interesting about that, looking at weekly samples, was the variability itself seemed to be very important for relating to the variables that we had about each subject, and each sample.

And so it’s entirely possible that the variability itself was going to wind up being really important. But of course, it’s also a lot more difficult and a lot more expensive to look at than just looking at a single snapshot. And so the single snapshots are still very valuable, I meant to say, even though you could potentially get more information by looking at the dynamics than you would from a single snapshot.

It’s like having a video of an event can often be very informative, but that doesn’t mean that photography has vanished as a discipline despite the fact that we all carry around little video cameras on our cellphones.

[26:08] [Damien Blenkinsopp]: Great.

So in terms of the variability, is it looking that that’s a positive or a negative association? Maybe you can’t really call it yet, but have you got an idea on which way it would be going? Like, for instance, is it potentially that the microbiomes when it’s healthy it’s able to adapt a lot more to the day to day situation, travel and all those things, so it would vary more. Or have you got any insight on that yet, or ideas on which way it might go?

[Rob Knight]: Yes.

So we don’t really have enough information at this point, and as you say it could go either way. Either you might want to see a fair amount of flexibility in your microbiome to be able to adapt to different circumstances, or you might want to see more resilience, and if it’s wandering all over the place it’s more likely to fall off a cliff, and to input the community configuration.

Right now we don’t have the basis to discriminate between those two. Most of the variability studies have been done at baseline in healthy people, and that doesn’t necessarily let you conclude anything about disease.

Most of the disease studies have looked at a relatively small number of samples. Often just a single sample where you’re looking at a case controlled paradigm where you round up some healthy people, round up some sick people, and you look at the differences at that state. So, really we’re waiting for the right kinds of studies to be done for variability in these diseased populations.

[Damien Blenkinsopp]: Great, thank you very much. I mean, we could get a couple of guidelines, just for people who are already using American Gut or one of the other services.

[27:26] I’m actually just about to take some antibiotics, for instance, so I’ve got a kit I intend to use, and then once the course is finished I intend to use it again. And actually based on your presentation, I intend to do one 30 days later to see if it will recover. Is that something reasonable as a baseline experiment? Just to see what’s going on.

[Rob Knight]: Yeah, that’s certainly very reasonable.

You might want to look at Dave Relman’s paper, it came out in Pathobiology a few years ago. And what he had there was three subjects who were taking ciprofloxacin from a healthy baseline, and they measured how long it took them to come back.

What was interesting about that is three people, they all responded totally differently. But then it’s kind of difficult to figure out what you should say about that, because the sample size is only three, and they all responded very differently from one another. But it’s certainly reasonable.

One thing that’s very interesting at the moment is the concept that maybe you should freeze your stool before you take the antibiotics, so that you could potentially replenish the members of your community. And again I should point out that that’s still in its very early stages as a therapy. This is not medical advice or anything.

But the concept that you might want to have that material available in case we figure out how to replenish your microbes from it later, kind of the way people are saving their cold blood for the stem cells. It’s certainly very interesting, and has a lot of potential.

And of course, right, you’ll be hoping for is that in the relatively near future – and there’s a lot of companies and a lot of academic research groups interested in this now – the idea that you might not actually have to take the stool itself, but rather isolate just a few of the beneficial microbes from it, encapsulate those into a pill and swallow those, for example. That’s shaping up to some very interesting research direction, although at this point it is very much in the lab and not in the clinic.

[Damien Blenkinsopp]: It does sound safer, also compared to the current fecal transplants. I think one of the concerns of fecal transplants is we don’t really know what’s in them.

[Rob Knight]: Yeah, that’s exactly it.

[Damien Blenkinsopp]: You know, because just the state of technologically today.

While you might make someone better in some extreme cases, like C. difficile, obviously that’s helpful. But for someone else who has maybe taken a lot of antibiotics and they had gut issues, to take a fecal transplant could be seen as a little bit extreme, as currently we’re not exactly sure what’s in it, and we could be putting something in there that we’ll discover later is not such a good thing.

[Rob Knight]: Yes, that’s certainly a concern. I’m on the science advisory board for the American Gastroenterological Association’s Microbiome Center, and one thing we’re actively trying to set up is a long term registry for fecal microbiome transplant, essentially so that we can track people who’ve had them over time, and make sure that it remains effective.

So for Clostridium difficile associated disease, it’s remarkable effective. Like 90 to 95 percent effective in many different studies. And the last large scale study comparing it to antibiotics for C. diff actually had to be stopped early because the people who got the FMT were responding so well that it was unethical to continue withholding FMT from the people who were on the antibiotics.

So, how widely that’s going to work for other conditions, we don’t really know. One thing you can do for antibiotic associated diarrhea that’s very effective is probiotics. There’s a number of different ones that are now pretty well supported by clinical trials at reducing both the severity and duration of antibiotic diarrhea.

And so in general, it’s not because the organisms themselves are establishing in your gut, but they’re creative a favorable environment where they can crowd out the weeds, like the proteobacteria and things that often come back after antibiotics. And essentially they’re creating more favorable conditions for your own microbes to come back.

[Damien Blenkinsopp]: Great.

[31:06] So, to kind of backtrack a bit. So in the presentation I saw, you saw after the antibiotic treatment, which was a baby with earache I believe it was, the microbiome pretty much came back to where it was before.

[Rob Knight]: Yup. But remember that’s an n=1 study, because we just had one kid in there. Yup.

[Damien Blenkinsopp]: So is that a possibility for some? We always talk about antibiotics like it could be potentially permanent. Because everyone’s pretty concerned. I’m pretty concerned when I’m going on a course of antibiotics now what kind of impact down the line is it going to have.

But it seems like it can depend on the severity, because antibiotics are used in many different cases. They can be used for a couple of days in some cases, sometimes, and there’s lots of different forms of antibiotics, which have different impacts as well, and potentially more severe or less severe.

It seems that in some cases the microbiome may be able to recover, and in other cases it’s not able to fully recover, and it’s quite variable for the moment, I’m guessing. Or do you have any insights as to the insights of antibiotics and how it varies?

[Rob Knight]: Basically what we know at this point is that different antibiotics have very different specificities, so they’ll target different bugs when they’re growing in the lab in isolation. We know a lot less about what effects the antibiotics have in more complex settings. And so the same microbe might only be targeted by antibiotics in some stages in it’s growth cycle.

And so Pete Turnbaugh, he’s now at UCSF but did this work while he was at Harvard, did some very interesting research looking at the effects of the same antibiotics microbes in different communities, that had come from different individual people. And so what he found is even if you have the same microbe, whether the same antibiotics would target that microbe depends a lot on who it came from.

And that’s very interesting. It just suggests that there’s a lot of complexity that we don’t understand at this point about how microbes are going to be targeted by a particular antibiotic, or will escape that depending on what other microbes are around. Depending on whether it’s expanding its population or contracting it, and all kinds of other factors.

So I think we’re just right at the beginning of understanding what’s going on in the complex situation of the human body itself.

[Damien Blenkinsopp]: Yes, absolutely.

[33:16] I think a bit of context to that is if you look at the size of DNA in our genetics versus the microbiome, right the microbiome is a lot bigger, and we don’t fully understand DNA yet. So, basically is it a much bigger task to understand the microbiome?

[Rob Knight]: Yes, it’s a tremendously more complex task. So each of us has about 20,000 human genes, but the size of the microbial gene catalog is somewhere between 2 and 20 million. So, by that measure you could say that we’re only about one percent human, and about 99 percent microbial in terms of the gene counts that we’re carrying around with us.

And so, on the one hand understanding it is tremendously complicated. On the other hand, if you look at other fields where there’s tremendous complexity, like say nutrition for example, but if you ran a potato through the mass spec you’d see all these compounds that you’ve never seen before, and that you don’t understand, and that don’t appear in any catalog from any chemical company. On the other hand, that doesn’t mean that we don’t know a fair amount about what happens if you rely on potatoes as your main food source.

And additionally, if you look at, for example, a lot of chronic diseases from a century ago, so things like rickets, goiters, and so on. A lot of those kind of diseases have just been completely eliminated by knowing that there’s some nutrient that if you give it to the whole population, like for example iodine in salts or fortifying milk with vitamin D, fortifying flour with thiamin, and so on, you can just eradicate these diseases from the whole population.

And so, in the same way it’s going to take us a long time to understand the microbiome, but it might not take that long before we understand how replenishing some of these microbes might potentially be really important for addressing some of the chronic diseases that affect us now, including many of the chronic diseases still linked to the immune system.

[35:11][Damien Blenkinsopp]: Great, great. And there are also macro levels. It’s a pretty good example, I think, you just gave nutrition, because we look at the macros and there’s lots of discussions about proteins, fat, and carbohydrate breakdown in diets. And in the same way there’s macro levels of our microbiome, right? There’s groups of Firmicutes and Bacteroidetes and others on a macro level, which I guess you could see patterns with those as well, and don’t necessarily have to dig down to the fine levels.

[Rob Knight]: Yes. That’s exactly right. Although in the same way that micronutrients are really important, some of the rare organisms might be really important.

And a useful analogy is something like Yellowstone National Park, where the reintroduction of wolves caused a profound change to the ecosystem. But if you go to the park – and not without, but you’d never get permission to do this right – but if you went to the park, and you round up say a cubic kilometer of material and then run that through DNA sequencing, you wouldn’t find a lot of wolf DNA.

And the reason why we know their important is you know people shot them all and the ecosystem changed, and they reintroduced them and the ecosystem changed again. So on the one hand, what technology is that we have right now, we’re probably missing the equivalent of the microbial wolf that could be playing really important roles.

On the other hand, if you were trying to understand that ecosystem, you’d be crazy to ignore the pine trees and the bison and the other really abundant taxa as well. So you can tell a lot looking at what’s common as well as needing to know what’s rare to fully understand the system. But I think we’ll be able to do a lot with the understand that we have now.

And it’s important to remember that that understanding has increased dramatically just in the last decade. So in 2005 it was a major achievement to sequence the gut microbial communities out of three people. And that was expanded by a fifth to hundreds of people, and then to thousands of people. And we’re just getting a much broader picture of what kind of microbes are in there, and what their roles are in responding to different things.

And so, the idea that you might be able to look at the microbes in somebody every single day for a year, would have been an impossible dream in 2005 but the technology has gotten so much better that it’s been done for a number of people now. And the prospects for developing further technology to open that up to the whole population I think will totally transform what we can know about microbial sides of yourself.

So, being able to push that additional technology development forward I think is one of the most critical things we can do at this point.

[Damien Blenkinsopp]: Excellent, thank you very much.

[37:44] One of the things we kind of skipped over but I thought might be interesting for the audience is you spoke about probiotics being useful in connection with the antibiotics treatment, and specific types of probiotics.

Do you know specifically what those are? Or could you point us to any papers which highlighted those? And in terms of the timing, do you take them while on the antibiotics, or is it a post treatment?

[Rob Knight]: The different studies that have been done at the moment haven’t really had a lot of consistency in methodology, so it’s difficult to make specific recommendations. It’s a fairly complex topic. I cover this in a reasonable amount of detail in my book, Follow Your Guts, which is just coming out tomorrow. But essentially I give a few examples of pointers to studies that have been focused on individual probiotics that have shown to be effective for particular conditions.

So one thing to remember with this is although there’s a tremendous amount of enthusiasm to probiotics and they’re very widely available, most of the specific products don’t have any particular evidence backing them. And so it can be a bit daunting to wade through the literature and try to find the ones that are actually supported by clinical trial data.

At the moment, at least to my knowledge, there’s no really good resource that summarizes the clinical trial information to tell you what species, what strains, and what products containing those strains have actually been shown to be effective. Although that’s something that’s a clear opportunity, where if someone sets it up that will be tremendously valuable for the public, especially given the level of enthusiasm.

One problem at the moment is, in the US at least, that the FDA’s official stance is that a dietary supplement can’t modify a disease endpoint. So as a result, if you find that your product actually does modify a disease endpoint, then it gets re-regulated as a drug, and so the manufacturing standards are certainly much more stringent.

And so if you want your yogurt with live and active cultures to continue to be a buck or two a cup, rather than being a thousand bucks a cap, which is about what it would cost if you had to manufacture it as biologic, there’s that issue to consider as well. So, that’s also a substantial problem for research in this area.

[Damien Blenkinsopp]: Right, so again, in that case we’re kind of hoping that no one tries to do clinical trials with the probiotics in products. It’s kind of no-win situation in that respect.

[Rob Knight]: Well it is a bit of an issue. It’s sort of like the issue with dietary supplements for athletic performance. So any time one tends to actually be effective, like say steroids, for example, it gets banned immediately. So you can draw your own conclusions about the effectiveness of the ones that are still on the market.

[Damien Blenkinsopp]: I guess one of the nicer things about that is currently when we take antibiotics it’s not really acknowledged that it causes any specific disease, although people may have gut upsets and any issues like that.

So I guess if these supplements continued to be marketed, and perhaps trials are just done on the basis of changing microbiome, that wouldn’t interfere because it’s not a disease endpoint. A specific disease endpoint, as I understand it, would be a specific classified disease, which is currently basically regulated today. So as long as they stay out of those disease areas, is it not a problem?

[Rob Knight]: Yeah, that’s exactly right. And that’s in part why as a consumer, it’s often very frustrating to see what claims are being made because those claims are now typically very carefully worded and very carefully negotiated.

[41:05][Damien Blenkinsopp]: So I know that you’re also involved in the Ancestral Microbiome Project.

[Rob Knight]: Uh-huh

[Damien Blenkinsopp]: Could you give us a quick update on how far you’ve got with that, and also what it is for the people at home.

[Rob Knight]: Sure, absolutely.

So the goal of this project is essentially to compare the microbiomes of different people living relatively isolated lifestyles and seeing whether they contain microbes that we as Westerners have lost with the hygiene or antibiotics. Or diets perhaps, that cause us to lose some of those kinds of microbes that could be beneficial.

There was a paper that just came out two weeks ago led by Cecil Lewis at the University of Oklahoma on the Matses who are a group of hunter-gatherers in Peru. There’s another one coming out soon that I can’t tell you about because it’s embargoed. But there’s some ongoing work that we’re doing with the Hadza in Tanzania, and the project that’s led by Jeff Leach.

So the Hadza are the last hunter-gatherers in East Africa in the Rift Valley where, of course, humanity evolved. So they’re the last group that’s still exposed to the microbes and to the mammals and to the plants that we would have evolved with during our early evolution. And so they’re very exciting to look at from that standpoint.

But basically the idea is to compare different groups and to understand first there’s still anything that they have in common that we might have lost more recently. And then the second thing is that try to understand similarities and differences in different human populations in terms of their microbiomes and how those microbes relate to different lifestyle features, to human genetics and to other factors.

It’s going to be incredibly fascinating from a science point of view. And from the point of view trying to figure out how our microbiomes should be shaped to optimize health.

[Damien Blenkinsopp]: Yeah, this is great.

I understand that Jeff — have you spent time with the Hadza as well, or has it just been Jeff that’s spent the time with the tribe?

[Rob Knight]: I went there for a week last year. It was just a spectacular experience.

[Damien Blenkinsopp]: I understand that Jeff, at least just spending time there, his microbiome changed. And he also used a fecal transplant from the Hadza to see a more extreme change.

But what I thought was interesting was just living amongst them and spending time with them, he saw some changes in his microbiome also. But I guess you haven’t had your sequenced yet, but potentially over that week you would have seen the same changes.

[Rob Knight]: Possibly. We don’t have the sequence data for that, although that would certainly be interesting to look at.

I should note that’s also true if you start living with a new partner, for example. You’ll converge on their microbiomes relatively rapidly. And one thing of interest at the moment is trying to figure out how much your microbiome records about the people you’ve lived with and the places that you’ve lived.

We don’t really know the answer to that at this point, but it’s certainly interesting to think about.

[Damien Blenkinsopp]: Well it is, just from a health perspective as well. Especially as it’s getting quite common to have IBS and things like that these days. It kind of makes you question these kind of things. How communicable is it, or not? I guess there’s a lot.

[Rob Knight]: Yeah, that’s a great question. I don’t [think] there’s been done a lot on communicability of IBS, but there are some probiotics that have done pretty well in clinical trials for IBS.

[Damien Blenkinsopp]: Yeah. So we’ve got a solution anyway.

[Rob Knight]: Yeah, and it has been linked to the microbiome by a number of different studies including some work we did with [unclear 44:25]. So yeah, it’s definitely a fascinating area. And the potential that some of these conditions could have microbial cures as well as microbial causes is very interesting.

[Damien Blenkinsopp]: Great, thank you very much Rob.

[44:40] So what are the best ways for people to connect with you, and learn more about you and your work?

[Rob Dunn]: Well, my TED Talk is a really good starting point. There’s a book associated with that Talk called Follow Your Gut, which is going on sale tomorrow actually.

[Damien Blenkinsopp]: Is that on Amazon?

[Rob Knight]: Through Amazon, and also I think it’s available as an iBook through the Apple Store. That’s a good way to find out more. It’s a relatively short book. The idea is to make it a friendly general introduction rather than going into a lot of technical detail about a whole lot of names that you’ve never heard about.

And also it’s got an Appendix that gives you a good overview of how you should interpret your American Gut results, and what things you can and can’t learn at this stage, and what we hope to be able to find out from us in the future.

[Damien Blenkinsopp]: Great, we’ll put links to all those in the show notes.

[45:22] Are there any other good books or presentations for people interested in the microbiome in general, and learning more about it? Are there any references that you commonly give out to people, which are good resources to check out?

[Rob Knight]: Yeah, Marty Blaser’s book. So Marty Blaser’s book Missing Microbes is fantastic, and really gets into a lot of detail about how hygiene and antibiotics may have led to the rise of a lot of autoimmune diseases, and other chronic diseases that are a problem today. And also one specifically about the dangers of over prescription of antibiotics. So I definitely recommend that one.

Ed Yong’s blog, Not Exactly Rocket Science, routinely covers microbiome topics. As do Carl Zimmer’s columns. Michael Pollan wrote a very nice piece in the New York Times in 2012 called “Some of My Best Friends are Germs,” and he’s continued to cover the microbiome on and off since then. Those pieces are all very good.

Jonathan Eisen and Jessica Green both have talks that are available through TED. Jonathan’s talk gives a very good introduction to what microbes are and what they do out there in the world. And Jessica’s features, it’s focused more on the built environment. And it’s talking about the relationship between the microbes in our bodies, and in the spaces we inhabit, and how we might want to design buildings that are green not just in terms of the plants, but also in terms of the microbes. So not just energy, but also microbial use.

So those would be some really good places to start. There’s definitely a lot of more technical resources out there, but you can probably get to those from the ones that I mentioned. And especially the references in Marty’s book and in my book are a good place to get started with more technical material.

[Damien Blenkinsopp]: Great, thank you so much for that. That’s very extensive, clearly.

[47:11] So I’m also interested what your personal approach is to body data, whether it’s for your health, your longevity, or your performance. Do you track and metrics or biomarkers for your own body on a routine basis?

You’ve already said that you take stool samples every single day. Is there anything else you do? And those stool samples, just by the way, for instance if you go to the toilet twice per day, do you take two stool samples, or are you taking one per day?

[Rob Knight]: Initially I was taking one per day, and I’m trying to capture all of them to the extent possible.

So in terms of auxiliary data I must admit that I’m not nearly as diligent as some other people who are interested in this sort of thing have been at tracking every single thing they’re doing every day. In part that’s informed by some of the studies where people have tracked a tremendous number of measures and not seen a lot. So that’s been relatively difficult to justify that level of additional time commitment.

Mostly what I’m tracking are things like, so periodically I’ll do a food and dietary inventory. Tracking things like travel is important. I would track medications except I essentially haven’t had any during that interval. But it’s the sort of thing that I would keep track of if it became relevant. That kind of thing.

[Damien Blenkinsopp]: Great, great. I’m guessing that most of these things are something that you’re doing in the realm of science, because you’re exploring the specific subject.

Do you think you would control for any of these if you weren’t involved in the science itself, out of a personal interest? How would you kind of modify that, if you weren’t currently studying you as an n=1 experiment to further the science? On a personal level, what kind of things do you think you would be doing?

[Rob Knight]: All kinds of things are interesting, it’s just a matter of how much time you’re willing to put into it, and how much money. So it would be very interesting to do blood and urine metabolites frequently, perhaps even daily.

It would be very interesting to get finer grade resolution on fitness, like with an activity tracker, that kind of thing. Given what we’re now starting to find out about brain microbe links it might be really interesting to, for example, track EEG readings over time and draw those microbial data.

You could even imagine doing like an MRI of yourself every day to see whether that complex multifarious specs tracks what the multifarious specs to find biomarker biome. Although that’s definitely a level of efforts and expense that it’s just not worth it at this point.

But what I think this is one of these things where the more data you have, the more potential you have to find out something really interesting that you wouldn’t have expected.

[Damien Blenkinsopp]: Great, thank you so much.

[49:44] The last question, what would be your number one recommendation to someone who is trying to use data in their life for better decisions about their health, their performance, or longevity? Something about their body. What would be your number one recommendation on how to use data effectively?

[Rob Knight]: There are a lot of different ways that could answer that question, but I guess my number one recommendation would be that what’s in the literature, like randomized controlled trials about what works and what doesn’t, are probably a really good guide as to what you should do initially.

Now, you might want to modify that based on observations of your own body, because anything that’s in the literature has got to be based on population averages. And one thing we know about people is that there are tremendous amounts of variability. So what works on average in the clinical trial is not necessarily going to be what works for you individually.

So, start with solid evidence from clinical trials, especially randomized placebo controlled trials, and then modify that based on your own observations about your own health whether it’s meticulously recorded, and you have over a long enough period of time that you have reproducible observations, not just off one anecdote.

[Damien Blenkinsopp]: Thank you there for some great insights into randomized controlled studies, and the averages also, which comes up sometimes on this show. Averages don’t necessarily mean you. So thank you for reinforcing that point.

Rob, thank you also for making time available today. I really enjoyed this show. You’ve obviously got a very, very deep background in this stuff, and we covered a lot of material. Looking forward to read your book also.

[Rob Knight]: Okay, great. Well thanks Damien, and thanks again for your interest in this, and this is only going to get more exciting as we find out more and more about the microbiome.

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A couple of cutting edge and very relevant quantified body topics today- quantifying the microbiome and the state of crowd science

We’re looking at the microbiome, which you probably have seen is the big new topic in the health media and news the last few years. Research is increasingly relating differences in our microbiomes to a range of disease conditions, primarily chronic and gut related ones. If you’re already buying the probiotics or prebiotics in the health store – the reason you’re doing that, is for the microbiome.

But what, if anything, do the probiotic and prebiotic products do for us? How dangerous is taking antibiotics – through changes they make to our microbiome? How does what we eat influence our microbiome?

It’s hoped that quantifying the microbiome, understanding what types of bacteria and other things make it up, will provide a lot more insights into our microbiomes – but how far has the science behind quantifying it advanced? How reliable is it? – and can it lead to us making decisions that improve our microbiomes that in turn lead to better health and less disease.

As we’ll see this is really cutting edge currently – and changing fast. But we have an excellent guest today to bring us up to date on all this.

Jessica Richman, is CEO and co-founder of uBiome. uBiome is the largest crowd science, or citizen science driven project to date. uBiome, already the most popular of the consumer microbiome services, is just about to go through a revolution thanks to recently having gained significant funding, and the backing of Y-Combinator as well as many big name investors such as Marc Andreeson and Tim Ferriss.

“The best ideas are not the ones in our building because you can’t hire everybody in the world who is thinking about your problem. The best ideas are out there in the crowd somewhere and the idea is to bring [those ideas in].”

Jessica, herself, has an impressive background having started and sold her first company in high school… and having accumulated countless scholarships and awards in academic institutions including Oxford and Stanford universities since. Her major interests include network analytics, innovation, collective intelligence, and crowd science.

The show notes, biomarkers, and links to the apps, devices and labs and everything else mentioned are below. Enjoy the show and let me know what you think in the comments!

itunes quantified body

Show Notes

  • What the microbiome is and how it varies across our bodies.
  • The many different aspects of the microbiome (bacteriophage, fungi etc) and why uBiome provides solely data on the bacteria in your microbiome in order to deliver their service at the low $89 price point.
  • The different areas of health that the microbiome and its status and and is increasingly being linked to in research studies.
  • Different approaches to quantifying the microbiome and their accuracy: cultures vs. microarrays vs. next generation sequencing.
  • 23andMe’s model for delivering consumer based low pricing via focusing on genetic SNPs (Single Nucleotide Polymorphisms).
  • The 5 body sites that you get quantified with uBiome (the same used in the Human Biome project).
  • How uBiome is avoiding the FDA regulatory landmine that 23andMe got hit with and which forced it to cut down the information, range and depth of services they were providing to consumers.
  • Citizen science or crowd science and what it means for the future of science and potentially the medical world.
  • Comparing different sequencing methods of uBiome, American Gut and others and progress being made to one common standard.
  • What should we be aiming for in experiments we run on our biome? Diversity? different ratios of the different types of bacteria?
  • The value of getting a baseline sequencing of your microbiome now to compare with in the future (especially if you should get chronically ill in the future).
  • Do probiotics impact the microbiome? If so, how do they impact it? Conflicting anecdotes, research studies and “marketing hype” from all the probiotic supplements and foods now available.
  • Personal insights from Jessica on how what she tracks about her own body, experiments that have worked, and her top 3 recommendations for people trying to improve their bodies and health through the use of data.

Give some love to Jessica on Twitter to thank her for this interview.
Click Here to let her know you enjoyed the show!

Lab Tests and Devices in this Episode

  • uBiome Microbiome Sequencing: The lab tests discussed in this episode. These can be ordered by anyone and done from a kit sent to your home.This is a sample chart output from their interface with my sequencing showing that I have more firmicutes and less bacteroidetes than the standard person on a paleo diet:
    damien-paleo-biome
  • 23andMe: The largest and cheapest service for getting your genetic sequencing (a subset of your total genetic makeup).
  • American Gut: The other main consumer microbiome sequencing company (not for profit).
  • Ketonix: The breathe analyzer for assessing your ketone body levels and whether you are in a ketogenic state. We covered this topic in detail in a previous episode with Jimmy Moore.

Other Resources Mentioned in this Episode

Jessica Richman & uBiome

Other People, Resources and Books Mentioned

  • The Human Microbiome Project The original NIH (National Institutes of Health) funded project to first sequence the human biome between 2007 and 2012.
  • Ilumina The solution uBiome is using to do their next generation sequencing of the biome.
  • 23andMe’s regulatory conflicts with the FDA
  • Jeff Leach Jeff heads up American Gut and has published his own self experiments to change his gut and move it towards a more diverse gut microbiome by interacting with Hadza hunters from Tanzania (read about it here)
  • Chris Kresser Chris, a functional doctor who works with patients on improving their gut microbiomes, has discussed that taking probiotics doesn’t change the microbiome’s makeup, but seems to impact it in via other changes or modulatory effects.
  • Probiotic foods: Jessica says she feels better with Quest Bars, while Damien has noted anecdotal beneficial effects with this Kefir product.

Full Interview Transcript

Transcript - Click Here to Read

[Damien Blenkinsopp]: All right Jessica, thank you very much for being on the show.

[Jessica Richman]: Hi, it is great to be here. I am really grateful for the opportunity.

[Damien Blenkinsopp]: Sure. So to kick it off for you, let’s talk about what the microbiome actually is. I understand it is not just the gut. So how would you describe the microbiome?

[Jessica Richman]: The microbiome are organisms, the microorganisms, that live on or in all of us. And there are many different microbiomes in the body. I think we should take a step back first though and say why is it called the microbiome? What is a biome? So a biome is an ecological area. So in the macrobiome, the biome that we are part of – you can be part of the rainforest, or a desert, or a tundra. And these are environments in which organisms live. And in the body, the microbiome where it actually could be anywhere, not just in the human body, but the microbiome are the microenvironments live in. So if you think about it, it is very different living inside your nose than it is living on the surface of your nose. So inside your nose it is windy, it is warm, it is slightly wet, and there are immune system interactions with human cells. On the outside of your nose it is probably colds, it is dryer, it gets sunlight, there are different kinds of cells that the bacteria are interacting with and if you think about it, it is a very different type of place to live for a bacteria.

[Damien Blenkinsopp]: So you could use the analogy of looking at the world and the jungles, the deserts, and all these different kind of things living in them?

[Jessica Richman]: Exactly, right. And if you think about it the outside of your nose is much more like a desert and the inside of your nose is more like the rainforest, let’s say. It is a very wet environment for an organism to live in. So if you think about it that way, it makes sense that there are microbiomes all over your body and all these spots have very different types of organisms in them and the microorganisms are very influenced by the environment they are in and what can survive in various environments. it is very different, just like plants of the rainforest don’t do very well when they are in the desert. But microorganisms that normally live in the rainforest die off when they are put in the desert. And it is not just bacteria, of course, there are also other microorganisms.

So there are fungi and yeast and all sorts of other organisms that live there and there is this whole ecosystem that we were just never able to see until recently because now it has just become less expensive to sequence the DNA on these organisms, some of which can’t be cultured. So previously you would figure out what was living there by trying to grow it in a petri dish, but that means you have to have the right food, the right conditions, it has to be able to be grown in that kind of environment and not all organisms can be. So now we are finding out things that were just impossible to see before. So now we know more about the microbiome and we have learned that my nose, the inside of my nose, is much more like the inside of your nose than my nose is like my foot, let’s say, because these are very different environments.

Our feet have more in common – the same spot on your body but very different types of places. So the NAH funded a project called the human microbiome project which was sort of supposed to follow after the human genome project to learn about the human microbiome, and they looked at 250 people and they established a lot of the sort of basic technology for doing this. And what we do with the biome is we have scaled up that technology and made it possible for anyone to have access to the same technology to understand what is in their microbiome at various sites and then what to do about it.

[Damien Blenkinsopp]: Is this like PCR DNA analysis?

[Jessica Richman]: So it is next generation sequencing, which is – there are a number of different platforms but kind of the leading one at the moment is by a company called Illumina, and they make what is basically a camera. It is funny, we just got one, and it looks like a printer/scanner – like an HP printer/scanner combo, one of those things you buy at an office supply store. It looks like that but what you actually do is you put a tiny tube of liquid in it that has the DNA in our case of 500 different people’s microbiomes, and it is seriously a tube that is less than an inch long. And you stick it in there and it is a camera that takes pictures of each of the base pairs of the DNA as it goes along and then tells you what the base pair is. So it is really amazing technology. They have really, they have changed the world.

[Damien Blenkinsopp]: So just to be clear, is that something you are going to be using or is that what you have used to date?

[Jessica Richman]: Yeah, so that is what we use right now. So right now we do next generation sequencing and we have been sending that out to various people to get – we sort of do all the processing and they just kind of – it is kind of like sending out your printing to Kinko’s or something. You prepare the document of what should be in it, and then they do the printing part. We have now brought that in house because we have brought in some funding and we sort of have the opportunity to bring it in house, which gives us a lot more flexibility, it is lower cost, we can do things faster because it is right here. So this is the technology we have been using all along and this enables us to really, inexpensively, make consumer price points for $89 to be able to tell you exactly what is in the DNA of all the bacteria that are living in your microbiome.

[Damien Blenkinsopp]: Yeah, so what are the limitations of this? Just a minute ago you were talking about the fact that the microbiome has fungi and bacteria. Today even there are viruses, bacteriophage, viruses that infect bacteria, and all this crazy stuff that we don’t hear about but it is so super complex. So are you just looking at the bacteria aspect of it?

[Jessica Richman]: Yeah, so we have the capability to look at fungi and even to do full metagenomic sequencing, which is to look at every organism, all the DNA that is in the sample, whether it is bacterial or human or plant or from the food you have been eating or every bit of DNA that is in the sample. But we currently sell to consumers the bacteria because it is simpler, it is easier to compare, and we have more people who have those kinds of samples. But there are definitely things that we are developing for the future, products that we are developing for the future based on specific other slices of the microbiome, like fungi. And full metagenomic sequencing is really expensive – it is thousands of dollars so it is not really a good – there is this much consumer demand for that.

[Damien Blenkinsopp]: Right, so that people understand 23&Me is pretty well known and they took a similar approach. They are only scanning certain aspects of genetics.

[Jessica Richman]: Well, it is a little different. So 23&Me looks at snips. So they look at our single nucleotide polymorphisms that are specific parts of the human genome that are known to be correlated with specific research outcomes. What we do is we look at all the bacteria. So there are other technologies that some people use that are based on microarrays that will only look for certain bacteria. So instead of – it is kind of an intermediate point between a culture-based method. That is maybe too technical. With culture you say is X bacteria there, yes or no? Does it grow or not? And maybe it couldn’t grow or maybe you did it wrong, whatever so there is some fallibility built into that. With the microarray method you say are any of these 96 bacteria there? And it can check for all of them. WIth the next generation sequencing you can find everything that is there and we are selectively looking at just bacteria because it is sort of priced so that the consumers can pay.

[Damien Blenkinsopp]: And is this a selection of bacteria I assume there is going to be classification, or a library of what is known well today? Maybe there are just some things that we don’t know there. so does it see everything?

[Jessica Richman]: That’s true, yeah. Well, it is everything that is known plus all the things that we are finding. so there are some public databases of bacteria and what we have done is we have taken the public databases and then added our own and basically enhanced them and so we had it in – they are polydatabases so people upload a lot of junk to them that they think is a good idea to upload and they are not very well curated academically. So we have taken those databases and cleaned them up and streamlined them and added a bunch of things to them to make them better.

[Damien Blenkinsopp]: Yeah, I think what is coming across is that this is quite new and it is exploratory. So the human microbiome project, how long ago was that –

[Jessica Richman]: So that started in 2007 and went until 2012 and we started our company with a crowdfunding campaign, actually, two months after the human microbiome project ended. So we sort of had this – you know, my background is not in biology. It is in computer science and economics and I was doing PhD in computational social science and learning about applied math relating to social networks. And I just saw there is so much interesting information relating to biology and some of the same skills that I was learning could be applied to this new information that was coming out. So we started this project right after the human microbiome project ended. And it is really new. The human microbiome project was really groundbreaking and helped establish this whole field. and you can see the number of scientific papers that are related to the microbiome is on this exponential curve up as the human microbiome project progresses. but we decided to take this technology and bring it to the public.

[Damien Blenkinsopp]: Yeah, and so at this stage now, for the consumers, what do you think – what can they get from it, if they get their biome? First of all you have talked about microbiomes. So you do the gut, you do the nose, genitals, mouth?

[Jessica Richman]: Mouth, skin, and genitals. Those are the ones we currently do. So we have the technical capability to do other sites and we are going to be launching some products that relate to the skin, for example, between your toes and things like that. But at the moment we do those five because those are the five that were in the human microbiome project. So it sort of gave us a basis for the data and sort of sample collection procedures that have been well validated. Yeah, we sample all those microbiomes of those five different sites. Then what consumers can get out of it is they can see what is in their microbiome, first of all, and then how that compares to other people and then how it compares to existing studies of the microbiome.

So right now in our [user interface – 00:12:50], it is very nerdy. It is very [inaudible 00:12:52] from our crowdfunding campaign, but you can see what are your bacteria, how does your distribution compare to other people’s distribution of bacteria, and then you can learn a little bit about each of the bacteria that are in your sample and how they relate to existing studies, which studies involved with which bacteria we are building right now. And this should be out in the next few months, like two or three months. We are actively in the development process and this is software that will go a step further and give you much more data analysis about what is in your sample.

The cool thing about doing it now is you are basically biobanking your samples. So if you sample now it is not like it is lost and you missed your opportunity, it is the only way to sort of grab what your microbiome is like now and then as our interface gets better and as our data gets better that sample gets better but you can also compare it to future samples.

[Damien Blenkinsopp]: Right, so it is the same as genetics. Basically you will be able to re-examine that same sample and still be updated?

[Jessica Richman]: Exactly, but actually we store the data so we don’t need to re – we can resample it later if technology changes completely and we need to totally resample it we can do that. but we also have the data from that sample and let’s say you sample now and you are like, ‘Oh, that’s interesting, my bacteria are fine.’ But then six months from now you want to make a radical change in your diet and you said, you know, maybe I need to cut out dairy, I don’t know, and you try that. Then we can sample afterwards and we can show you the difference between those two things. And we will have the earlier sample so we will know what it was like before.

[Damien Blenkinsopp]: Right, so you are talking about things that influence it and I guess it is quite an important point to mention that your microbiome can change. There is a lot of emphasis on the gut these days. that is the one they talk about most in the press and stuff so i guess it is the one with the most research?

[Jessica Richman]: It is, it is the one with the most research and it is also the one with the most – it is the richest environment for bacteria and that is why the most research is done there, because it has the most bacteria of any site in your body. And also obviously because that is where you process food and waste, and it has the most biological activity relating to all parts of your body. So they found really interesting connections between that and the brain, for example, that are not what you would expect. There are really interesting relations between the microbiome and depression or autism or things that you might not expect, but they don’t say that, for example, about the nose microbiome because that is just less likely.

[Damien Blenkinsopp]: Right, so in terms of you just mentioned a few diseases and conditions – there were things like obesity mentioned, diabetes, acne, allergies. There is quite a range which are now linked in some research to the microbiome. How far along do you think that is? Do you think that has got quite a long way to go or do you think it is interesting for someone to say, who has one of these conditions, to get their microbiome done?

[Jessica Richman]: I think it is not that far off, and I probably think that because this is our field and what we are working on and we know the possibilities, that things can happen quite quickly. I think it is not that far off because we’re collecting all this information that can be useful in actually doing something about it. At the moment this is a consumer product and it is not intended to treat health conditions or diagnose health conditions, but we will have the information and when we do find something interesting we can then pursue the proper channels in making sure that it is available to people who have health conditions and need it.

[Damien Blenkinsopp]: Yeah, so I mean, you stepped on the 23&Me landmine.

[Jessica Richman]: Exactly. Well, we didn’t step on it. We were collateral damage or something.

[Damien Blenkinsopp]: So you said something very important there, it is a consumer and not a medical product. How is that evolving? Are there things that you have to do or are there limits? Can you give us an idea of how you are going to go over that?

[Jessica Richman]: We try to be really careful. And we try to be careful because we don’t want to get into the trouble that they got into, but also because there is sort of a really important public health responsibility to not give people information that is dangerous, poorly understood, that will lead them to do things that are bad for them without understanding why or mistakenly thinking they understand why. I think it is really important to do that. So we are careful to – we are sort of pursuing a two-prong strategy.

One is for things that involve diet, wellness, health, and people’s curiosity about science that is fairly safe in my view. And then things that involve serious health conditions, we are being much more careful with that and we want to make sure we have much more validated information and that we go through the right channels and that people have expert consultation with their doctors or even at the very least with clinicians doing research to share that information. I think it is just a matter of trying to be conscious. And there aren’t any written rules. There is nowhere that we can say, ‘Oh here is where the line is, let’s be careful to make sure that we are on the right side of it.’ But we are just kind of using our judgement at this point to make sure that we are thinking through the issues and trying to be responsible about how we give people information.

[Damien Blenkinsopp]: Yeah, good to hear you are thinking ahead. So we talked a little bit about things that can affect it. Do you know of any clinicians that are starting to either take this themselves or maybe send their patients to give them an idea? A lot of clinicians are trying to tackle things which aren’t very well treated or documented, like dysbiosis and IBD, all of these kind of gut issues, which at the moment is hard to find some clinicians who can say this is the exact approach to fix this. It is not coded and it is more of an art to say the least.

[Jessica Richman]: Right, there is no standard care for a lot of things. And that is difficult because patients are then left without a good answer, even though he went to the doctor to try to get help. I think what we’re doing at the moment is that this is not a diagnostic test. It can’t be used by a clinician, and I sort of want to underscore that. But we haven’t evolved in clinical research, so if a doctor wants to put together a research study of their patients or the participants that they solicit, we partner with them and we provide them basically with a consumer produc. But since they are a clinical researcher they can have a study and they can sort of design this study the way that they want and then communicate with their participants the way they want, which is a way to sort of frame it experimentally so that it is not basing a diagnosis on it or giving medical advice based on the test, but they can use it to learn things about the entire population of people that they are working with.

[Damien Blenkinsopp]: Right, and it can better inform the doctors instead of guesstimating all the time.

[Jessica Richman]: Exactly, right, And it can also press for publishable research. Some of the doctors are doing really cutting edge things and they want to add this to the repertoire and say oh, this is really interesting when i compare patient group X to patient group Y I notice X has this interesting thing, their microbiome, that is publishable research. So we are contributing to science through clinicians who were doing clinical research. A lot of the doctors that are sort of on the cutting edge also do research as well as treat patients, so they can kind of wear both hats.

[Damien Blenkinsopp]: Great, right. I know that this kind of connects with the topic that you are a big fan of, the citizen science?

[Jessica Richman]: Yes, don’t get me started!

[Damien Blenkinsopp]: We will definitely put a link to your TED Talk on that for background, but briefly, what is citizen science? What is that about?

[Jessica Richman]: Sure, so citizen science is a word for non-scientists, non-PhD researchers who work in academic labs. Sometimes they are people who have PhDs but aren’t researchers. They are contributing to science in some way. It started with – and actually, it is really interesting. So Susan Science, that term and the use of that concept, was started by ornithologists, who study birds. And there aren’t enough ornithologists who gather data about all the birds. So there are a lot of amateur birdwatchers who contribute to the science ornithology by spotting birds in various areas or by reporting on the things that they have seen.

So it started out there but this concept of involving the public in research is really just a type of crowd sourcing. So the term we use for uBiome now is crowd science, because I think it sort of communicates the fact that this is not about their citizenship or what country you are part of or whatever, but the idea that the whole crowd can be a part of science. And not just data collection, as in bird watching, but also hypothesis generation, funding of science, evaluation of science. We haven’t done all these things yet, but we really want to.

[Damien Blenkinsopp]: That is interesting because uBiome is basically – you just brought up a whole bunch of things. And that is what uBiome is.

[Jessica Richman]: Exactly. So our goal is to use the fact that people are interested in the microbiome, that it affects all of us, that we all sort of are potential research subjects because we have a microbiome and that we do think that change, to allow us to change the way science is done and to have people fund science, evaluate science, learn about their bodies, and contribute that knowledge to help others, and i think that it is really a change in the way science, which is this very institutional system, it is very much like the change from only four broadcast channels to like YouTube.

[Damien Blenkinsopp]: Right, that is a perfect analogy. It is about – this is taken from your talk, but it makes perfect sense. It is like participation – a good example I thought you gave also there, I mean, obviously YouTube allows anyone to participate and everyone sees people putting forth innovation, innovative content, and that then goes to TV and other places, which is a good analogy. If TV was science, now and again they will find something in the crowd which is useful and they will integrate it, so it is kind of like taking that participation.

[Jessica Richman]: Exactly, and then it makes it something everyone can do. I mean, YouTube is full of teenagers covering pop songs or something that would never have even been possible to be shared before because you would never waste your really expensive broadcast spectrum on something like that. But you don’t know who is going to be the next pop sensation and you can find that. And it is kind of a trivial example, but you can see that in the world of science and you don’t know who will come up with a really interesting discovery. And this was part of the theme of that talk, that I think it is not – a researcher who is paid to study an area is obviously passionate about their work and is an expert and what they are doing is really valuable. But a person who is suffering from that condition is also really valuable and I feel like they have been totally excluded from the system at this point and integrating in their own knowledge about themselves can add so much.

This is an example that I didn’t give in the talk but I think is really interesting. A friend of mine is a spinal cord researcher and she told me – I should probably verify this a little bit better. What she told me was really interesting. She said that the field of spinal cord research changed really dramatically when – most spinal cord researchers are not spinal cord patients. Most of them are not – they kept on working on trying to get people to walk. What they finally realized after there was a researcher who was a spinal cord injury patient who did a survey to say, ‘What do you actually want us to be researching?’ And it turned out that most spinal cord injury patients have accepted the fact that they are not going to walk, and that is sort of just the way it is. But what they want to be able to do is all the things we do. They want to be able to get around easily, they want to be able to sit comfortably. They want to be able to socialize, they want to be able to go to the bathroom comfortable.

They want all the things that we take for granted. And that is actually what they care about, not learning to walk again. That would be nice, but that is not affecting their lives as much as just basic quality of life now. And that really touched me because I thought, ‘How much time and money is spent researching the wrong things that patients don’t actually care about?’ Because it sounds really good. We are going to make them walk again. It just sounds like you are the great savior that is going to come in and solve all their problems. But maybe they want totally different problems solved.

[Damien Blenkinsopp]: Yeah, and you see a lot of communities which get kind of negative and fed up with the way things are being tackled and they are also the most motivated as well as all the passion and motivation because obviously it is effecting their lives. So if we could harness that motivation and passion that could obviously help push things forward. But it seems like citizen science, what it needs and what you spoke about is basically helping to organize and structure this crowdsourcing because obviously if everyone just goes off in their different directions and it is not controlled that is just a mess.

[Jessica Richman]: Yeah, I think so. And I think our role is to sort of create the infrastructure that makes it easy for people to study things. And that is what we want to do that helps us business wise and it also just helps us make that change in the world happened have the average person be able to have access to these cutting-edge DNA sequencing technologies that most people don’t have access to just by making it as simple as you buy a kit, you answer some questions, and then you get some results.

So I hope to see this in other areas too because I think there are so many things that are sort of very disorganized in the approach of patients who have them or even just subjects of interest, or things that people are just curious about and that greater scientific establishment is not super concerned with, whether [inaudible 00:25:28] is good for you, or something like that. Nobody cares about that because they obviously have much more important things to worry about in terms of public health but it is interesting to people. And I think people should be able to fund the research that they either desperately need or that they just are curious about, and I think that should be open to everybody.

[Damien Blenkinsopp]: I think that another analogy is that if you look at businesses as entities and the way they have evolved over time. It used to be from top down they would design products and push them on the consumers and that wouldn’t work so well but they have become these marketing – they are a lot more integrated, they look at customer feedback and in a way you are talking about applying that same concept to science as well, having this feedback mechanism which helps to direct the research also from the end user or the end benefitter.

[Jessica Richman]: Exactly. I think that is true. I mean, it is sort of changing from the sort of theory of the firm and having this institution that broadcast things out to people, to this network where people can interact in a much flatter environment. And I think that is very beneficial for innovation because it will help us, the best ideas. This was something we were talking about, we work with some researchers and they were saying the best ideas are not the ones in our building because you can’t hire everybody in the world who is thinking about your problem. The best ideas are out there in the crowd somewhere and the idea is to bring them in.

[Damien Blenkinsopp]: Well, it is very exciting. I hope you help to push that movement forward, obviously.

[Jessica Richman]: I hope so, too. It is something I care a lot about.

[Damien Blenkinsopp]: Well, it is these kinds of things which really change. It is a revolution rather than just an evolution. So that needs to be given efforts. So the other thing I wanted to touch on is obviously there are a lot of different things that can affect the microbiome. Some of the things we have spoken about so far is diet, right? Everyone kind of understands that diet can impact it. And we look at things like probiotics, prebiotics, dietary fiber, high-fat versus low-fat diet, artificial sweeteners have been in the news recently. How do you kind of look at the diet influence and how far – how much understanding we have? Is it a big impact? Is it a major impact? Do we have to look broader than that?

[Jessica Richman]: That’s a good question. So it is a major impact but the questions are teasing. it is a very complex impact. So the question is – and this our science team, is trying to figure out teasing apart those different effects, people who eat very healthy diets also tend to exercise a lot and be young and healthy otherwise, and sort of have this cluster of things that is sort of separating out what is the effect of diet. What is the effect of exercise?

And we are lucky with the microbiome – it is sort of a great feature, the microbiome, that changes over time in response to a change – we can say, ‘Okay, you are not much older and you are still equally healthy but you have changed your diet and here is how your microbiome changed in response.’ And we can see those differences. That is very interesting, but there are a lot of effects to tease out. We definitely see huge differences. Now that we have looked at thousands of these we can say, ‘That is a vegetarian,’ because you can just kind of tell by looking at the microbiome. Which is really kind of fun, actually.

[Damien Blenkinsopp]: My results are actually kind of weird, like compared to everyone’s.

[Jessica Richman]: Oh tell me more, interesting.

[Damien Blenkinsopp]: I have got very high, very low [inaudible 00:28:25] and very high [inaudible 00:28:30], so like 78%.

[Jessica Richman]: Interesting.

[Damien Blenkinsopp]: Yeah, so I was actually looking at the American –

[Jessica Richman]: The American Gut.

[Damien Blenkinsopp]: Right, the American Gut and Jeff Leach and what he is doing in Tanzania with the hunter-gatherers. Could you give your perspective on that? I am sure you are aware of that more than I am.

[Jessica Richman]: It is very interesting. Their scientific project out of the University of Colorado that is working on some similar things, and I think are differences that were not just America and not just the gut, so I said that was sort of a very easy comparison to make in that way. And also they are non-profit and part of an academic research project and we are for-profit. But I think there are also some technical differences in terms of the sample, collection techniques, lab extraction techniques that are really technical, but suffice to say there isn’t a standard microbiome extraction method and we both used well-documented, very much validated research methods, they are just different methods.

[Damien Blenkinsopp]: Well just on that, because there was a little bit of controversy on that when someone published that. Could you talk a little bit about that? Is that because there are differences in samples? Are there differences in the approach? Because the two samples came back a little bit different from the two companies.

[Jessica Richman]: There are a number of differences. They came back a lot different and I think the reason is – there are a few things. We used a different sample collection technique so when you sample with the American Gut they take a swab and they rely on the swab drying out so that it doesn’t change in transit. Basically, you just send back a Q-tip, or a sterile swab, in the mail. And it isn’t preserved in any way and there is nothing to freeze the DNA at that point in time. So it leads to – there is an argument to be made that it leads to overgrowth because things are growing as you are transiting in the mail to their lab and before the sample is processed.

[Damien Blenkinsopp]: And maybe some things are dying as well?

[Jessica Richman]: Well, dying is okay, because they are there. When you look at the DNA, dying is okay but it is other things from the air landing on it, growing in it, and then you think that was what was in the gut, not what was actually – you don’t know what happened after the gut. And everything that is there you see is there. And they do some correction for that with bioinformatics, but it just leads to different results. The results are biased in different ways.

Then as far as the actual extraction technique, we both use slightly different – and this is too technical, but we use slightly different kits for the extraction of the DNA that leads to different results, but it seems to me to there is a reasonable way to translate between the two based on that part of it.

[Damien Blenkinsopp]: Right, and you had a blog post on that.

[Jessica Richman]: Yeah, we did a blog post on that.

[Damien Blenkinsopp]: If people are interested in the technical aspects of that.

[Jessica Richman]: Yeah, we did a blog post on that and I think going forward it would be – one of the things we are really interested in is having a more standardized method so that everyone is kind of on the same page about what that is. And I know there are some academic standards with this, but we would love to be involved in that and do some comparison studies and sort of see how they compare. Because it is in everyone’s interest to have a standard for how microbiomes are measured.

[Damien Blenkinsopp]: Right, and they have that now for DNA, right?

[Jessica Richman]: Exactly.

[Damien Blenkinsopp]: So you just have to do the work, the collaboration to get to the same point?

[Jessica Richman]: Well, everyone has to agree. And getting academics to agree on things is really an emerging field. I think this has happened in many emerging fields with their different standards and everyone thinks their standard is the best. So us being no exception to that. So I think we are a little ways from having a translation between the two methods. I think that will be much more important as we move towards clinical results, where you actually want to get the same result everywhere that you do it. Where as in academic research labs this is far from uncommon – only 10% of the studies in the biological sciences can be reproduced. So this is not something that has never happened before.

[Damien Blenkinsopp]: Yeah, and this is a common point that comes up in this podcast, whether it is blood samples or heart rate variability, there are different standards at the moment because a lot of this stuff is still new. So I guess the rule for consumers if you start with uBiome, stay with uBiome so that you can compare. If you start with American Gut, stay with American Gut because otherwise you can’t compare your results.

[Jessica Richman]: Exactly. And we wish they were more interoperable, but that is the current standard. I mean, the goal of American Gut is a little bit different too. Their goal is to map the American Gut, what is in it, which is a really interesting scientific goal and very laudable, but that is different than our goal, which is to give consumers valuable information about their own microbiome while contributing to science. So that is a very different goal because our main focus is on giving the individual what they want and then letting them have more control over science.

[Damien Blenkinsopp]: So going back to Tanzania and [inaudible 00:32:55] because what was interesting there is it is difficult for us to know what we are aiming for, what is good, what is bad in the microbiome. You are doing interesting stuff at uBiome because you have these categories which, if you don’t mind explaining quickly, what you do there.

[Jessica Richman]: Yeah, of course. So we compare – we sort of pick – so in our new version these will be much more flexible than they are right now, but what we did not for this first version is we have specific categories of people that have very different microbiomes from each other and you can compare yourself against them. And you can say here is my comparison against vegetarians, people on the paleo diet, people who have taken antibiotics recently, people who drink a lot – exactly, people who drink a lot of alcohol.

So we sort of compare against those categories and those are interesting ones that we sort of see a really dramatic difference right away, so it is very interesting for people to do that. Compared to hunter-gatherer tribes, it is really interesting. I was actually talking to someone and we do research projects for researchers also. I was looking at vaccines in the developing world and we usually come at this from such a totally different angle because people assume that people in the developing world had the perfect gut and if we could only go back to our hunter-gatherer ancestors we would all be so healthy.

And I suppose that is true for chronic diseases, diseases of civilizations, but it is not true when you are very sick with acute illness because your water isn’t clean and you want to be vaccinated against it, for example. So it was really funny to have this conversation with this vaccine researcher who was saying this is really interesting. You are assuming that the gut of people in the developing world is better, but maybe that isn’t true.

[Damien Blenkinsopp]: But yeah, it is just true. The whole point is they are looking at the [inaudible 00:34:36] and other people because supposedly haven’t changed much over time. I think the most interesting thing that I saw there was the diversity. How important do you think diversity is because the argument was that the [inaudible 00:34:45] have a much more diverse microbiome, so that is good. Is that true? Is that for sure?

[Jessica Richman]: That is such a good question. Many studies have shown – I will answer this a bit eventually. Many studies have shown that there are positive outcomes correlated with diverse microbiomes. For example, there have been studies in elderly patients that when they are sicker, when they have less diverse microbiomes, and perhaps that is part of the moving to a more institutional diet as you move into assisted care or assisted living facilities or something. Part of that is the microbiome becomes less diverse and that is worse for you. There has been a lot of research about how eating a variety of foods, sort of following [inaudible 00:35:28] food dictums will make you have a more diverse microbiome and that is associated with a lot of healthy outcomes. So there is a lot of research and I think that it makes a lot of sense that it would be healthier.

There is also research about that a lot of health conditions are because there is a cornerstone species you just can’t get rid of, for example, C. difficile infections are one species that has sort of taken over your microbiome and that makes you very sick. So I think the evidence is there and the diversity is good, but the scientist in me to some degree used to say this is good and this is bad because there is always some kind of exception to that.

[Damien Blenkinsopp]: Yeah, and like we said before it is very early stages. So it is just kind of indicators. So I guess an interesting thing when I am looking at your biome now and if I compare myself to people taking antibiotics. Antibiotics are known to kill of bacteria of course and part of your biome. So everyone can kind of see, yeah, that is not a good thing for your biome. I think that is kind of commonly accepted now. So that is one interesting thing you can do in your biome, and sort of compare yourself to people taking antibiotics. Am I more diverse, am I less diverse, or the same. And to give you a rough idea of how healthy you are?

[Jessica Richman]: Right, what we want to do – I wouldn’t make the claim that it makes you more healthy but we can definitely say that with antibiotics, how were you before you took them versus after you took them. I think that would be really interesting. So it is not just you to the population, it is you to yourself. And so you get a sample now, a sample after you take antibiotics, and and then see the difference between the two. And then sample a few months later and see if you have gone back to where you should.

Because most people bounce back to where they were, where they feel fine and it sort of looks like that microbiome is very similar, but maybe that is not true of you and it would sort of be the only way to tell. So there is a lot of really interesting stuff there in terms of tracking your own health and sort of having a baseline that you store now, so you find out, for example, that you have Lyme disease or some other health condition that makes you take chronic, long-term doses of antibiotics, you kind of know back where you were when you started.

[Damien Blenkinsopp]: Right, and then at least you are like okay, I was healthy at that point, maybe I should try to get back to where I was in terms of my microbiome. So at least you have –

[Jessica Richman]: And some of this is all in the future but the part that is not in the future is we can store the sample now and we can tell you what is in the now. And the part that is in the future is okay, how do we get you back to where you were and how do we know what is a good change and what is a bad change. Those are all the things we are working on really actively and we should have some answers, not in the next few months but in the near future. but there are just a lot of really interesting things we can do once we have the data stored then we can kind of have a basis for comparison.

[Damien Blenkinsopp]: So there are a whole bunch of people doing experiments right now, and I think we can call that citizen science or crowd science, right – there are people taking dietary fiber. I am quite amazed because I just got back to the US and I am going into like Whole Foods and places, and probiotics is huge. It has grown out of proportion and you see even in the drinks, like half of the drinks seem to be probiotic drinks now. So obviously that is really, really pushed but to some people, like clinicians like [inaudible 00:38:20] if you know him, and he is like well, there is evidence to say that probiotics don’t change your microbiome that much. So in terms of experiments, you might do one yourself or you might think are kind of interesting, what kind of things would you think?

[Jessica Richman]: Oh, this is so good. So one of the things that we would love to do and that we are sort of trying to set the infrastructure for is to test out different probiotics on different people. Well, we won’t test it on them – they will take it and then we will test them and you know, of course, this will be part of us researching the effects of the probiotics on the individual. This will be part of a study where we can compare like to like. Like people taking like probiotics and sort of their outcomes. I think it is really interesting.

There are a lot of studies that show that either probiotics are mixed or that they don’t work. But then there are a ton of anecdotes from people, and we hear from them all the time, who say this changed my life. This actually worked. And I don’t think that they are all making it up or they all – it is all the placebo effect. I think it really is having an effect on some people. But the question is who and under what conditions and how do you know and what is it doing. And these are all really good questions.

[Damien Blenkinsopp]: Yeah, I guess from what we know it is not actually affecting the microbiome it is affecting something else. I mean, you call it the microbiome but maybe it is not the bacteria or who knows.

[Jessica Richman]: Right, maybe it is not the bacteria. I mean, it is an ecosystem there, right? So it could be –

[Damien Blenkinsopp]: Maybe it is protecting you from the yeast overgrowth. Or who knows?

[Jessica Richman]: It could be, right? Exactly. Maybe what you want is not the presence of that bacteria but the absence of something else. I think that part is probably the easiest. I think if it is doing something there is some mechanism, right? So that part we can figure out later. I think it was the most immediately useful to people who have questions or problems and want to take something but don’t know what or don’t know if it is worth it for them to do it. It is just to see what probiotics have what effects on what people. I think that would be really valuable.

[Damien Blenkinsopp]: I think it is really interesting in these areas where people are spending a lot of money. It is obvious to me that people are now spending a lot of money on probiotics and they are starting to spend a lot of money on prebiotics and you see all the supplements now and the people talking about resistant starch. If people are spending money on these things, I think it will be really useful when data actually starts coming out to prove it. The marketing always goes way faster, the hype goes way faster than any of this stuff really, and who knows – it is anecdotal. For myself, I think i do better with [keffir 00:40:33]. When I come to the US I love the [Keffir 00:40:36] so I will drink that and I tend to feel way better with that. But I have heard other people say that but who knows why or what that is about.

[Jessica Richman]: So don’t you want to – I mean, don’t have you have this natural drive to be like, why, why me? Who, and who else?

[Damien Blenkinsopp]: I will be doing another sampling of uBiome this month to see if that has change anything because I have doing more of that lately.

[Jessica Richman]: So I started eating – I don’t know if you ever eat Quest Bars, which have prebiotic fiber and it is [inaudible 00:41:02] invasively so they are indigestible fiber that is not supposed to count as carbohydrates. I feel differently when I eat them versus bars that have maltodextrin or something in them, and it is sort of obvious, digestible carbohydrate. So it is really interesting and we get to do a lot of experiments around here and just sort of see what the difference is.

[Damien Blenkinsopp]: So Jeff Leach is arguing that dietary fiber has a bigger impact on changing your microbiome based on his self tests. And what do you think of that?

[Jessica Richman]: So that is interesting. There are a lot of things you could say about that. And one, there are all those sorts of things. So I think the answer to all these thing is sort of more research. That is interesting, and a lot of things have been discovered by scientists looking at themselves and saying, ‘Huh, that’s interesting. I wonder why that happens.’ Or when I do X, Y happens, but I think you really do need – and what the crowd science lets you do and what the power of the internet lets you do is say okay, that is an interesting hypothesis. Now let’s have a thousand people test that and see what happens. Then you can find an answer to it. So I think that is the goal, and that is what is great about crowd science. It is not my opinion versus his opinion, it is his hypothesis versus the data that we see.

[Damien Blenkinsopp]: Right. I guess a good principle for the people at home is before you do anything get your microbiome done so that if you are going to take probiotics or you are going to take resistant starch or prebiotics. At least you can see what has changed, if anything has changed, especially if it has any health impact. Especially a negative one, and you want to kind of go potentially back to it in order to reverse that.

[Jessica Richman]: Right, exactly. Or even just to have it banked so that then in the future you will be able to win the science of therapeutics and diagnostics is caught up to the science of just processing the samples and the data will be there exactly.

[Damien Blenkinsopp]: So on that point, basically how stable do you see the microbiome in terms of we often talk about how often is it worthwhile and it adds value to track the data? Because it is not that expensive now, microbiomes, but it is relatively cheap and I assume eventually it will be even cheaper. But how quickly does the data change? We know that the microbiome changes but how long is it worthwhile?

[Jessica Richman]: We haven’t done the study. It would be really cool to just test everyone’s microbiome for a day, test 100 people’s microbiome for a day. And we haven’t done the study every day for like two weeks. We haven’t done the study yet but we have talked with certain partners about doing this. And we may be launching something about this. But there are research studies that have been done on this and there is sort of a change every two weeks for if you make a major change, if you change your diet you will see it within two weeks. Antibiotics of course act much more quickly but if you have a dietary change or a habit change you will see it within two weeks.

[Damien Blenkinsopp]: When you say a habit, what could that mean?

[Jessica Richman]: Let’s say you start running marathons or something. You start training for a marathon –

[Damien Blenkinsopp]: Exercise, or –

[Jessica Richman]: You exercise, you move, you travel to a different country and eat completely different food. I suppose that is a dietary change too, but you drink different water and it may not be that consciously you are changing your diet but you are in a totally different place.

[Damien Blenkinsopp]: We are still talking about diet a lot, but actually just if I am living in another country, it is the fact that I am touching things, if I am living in a different environment where the bacteria could potentially be different, or if I am living with a new partner, for example.

[Jessica Richman]: Right, well probably not your gut microbiome but definitely the oral microbiome changes when people start kissing a new person. So that makes sense.

[Damien Blenkinsopp]: Yeah, and the genital microbiome I assume, too.

[Jessica Richman]: Exactly, the genital microbiome as well. We do collect genital samples and we do ask questions about that, and it is really interesting. We are adding data insights for the other sites as we do for the gut microbiome, and it is really interesting.

[Damien Blenkinsopp]: I guess there are less people doing genitals because it is a bit more of a politically sensitive topic.

[Jessica Richman]: Yes, that is sort of it. Also, we sell it in a pack with the other sites. So yeah, I think there are definitely less people doing it but it is still kind of interesting, the kind of insights that you can come up with because you kind of see how people’s habits – and it may not even have entirely to do with sex, it may have to do with women after menopause, how is your microbiome different? Or different parts of your menstrual cycle, or in men if you are circumcised or not. Or if – you know, just sort of other things that are not directly related to sexual activity but have to do with your own body and how it changes over time.

[Damien Blenkinsopp]: Yeah, this is a fantastic subject. I would like to ask you –

[Jessica Richman]: It is always great to have genitals and mouths on the podcast.

[Damien Blenkinsopp]: For my next workup I want to get the whole thing but whatever, I would like to find it all out. I am not bothered about political sensitivities. So what do you think will happen in the next five or ten years in this area?

[Jessica Richman]: Gosh, I think it is going to be really exciting.

[Damien Blenkinsopp]: What are you excited about?

[Jessica Richman]: Oh, there is so much I am excited about. So I think there is going to be a real explosion of therapeutics, the proper word for this, but let’s describe that in a little more detail. I think that a real explosion of drugs, probiotics, diagnostic tests, and just really taking this data and doing something useful with it that helps out specific groups of people either with serious health conditions or even very minor health conditions like acne or athlete’s foot. I think there will just be this explosion of valuable products that come out of this kind of data. And I am really excited about that because I think there are a lot of really amazing problems we all have.

[Damien Blenkinsopp]: So out of interest, how would a product develop or work with you?

[Jessica Richman]: We do work with researchers that are doing this kind of thing and basically what we do are really big studies about specific questions. These really big study about specific questions, someone is looking at dandruff or if they are looking at athlete’s foot or they are looking at heart disease or autism or something, sort of a major – something with much more important consequences. We designed a study with them and then we partnered with them and they use our research techniques. And depending on the type of study, they will often just use our kits where we handle the whole study process for them. And they basically give the participant the uBiome product and then they also share the data so that they can use it for academic purposes to publish a paper about it.

[Damien Blenkinsopp]: That feels like a great model. That is real crowd science.

[Jessica Richman]: It is crowd science, exactly. And what is unique and what I really like is that in almost all cases the participant gets their own data too, which is really unusual in scientific studies. Usually you participate and maybe you even get paid to participate but you never get your own data. And I have never heard of a study where you get your own data. But here the participant gets to do their own study also at the same time. Their data is banked and they can access it later. They can do whatever they want with it and at the same time they are contributing to a scientific study that they find interesting.

[Damien Blenkinsopp]: The other exciting news for you guys is you have joined Y Combinator with [Anderson and Co. 00:47:52] and you have obviously got big investments now in terms of microbiome project and you are by far the biggest investment. And so correct me if I am wrong, but what does that mean for you and where you can take the company now?

[Jessica Richman]: So what we can do is we can scale up and we can make sure that the experience is as good as possible for the user, so revamping our website, revamping our boxes, and making customer service better. Like, all those sorts of things are just sort of making the experience better for people. But we could also be able to analyze the data in more detail and come up with really interesting insights for the participants so they could get valuable information. That is what that money is for, to sort of give us the resources to make things better much faster.

[Damien Blenkinsopp]: And a couple of personal questions before we finish, that would be great. What kind of data metrics do you track for your own body? Anything like the microbiome, anything else on a routine basis?

[Jessica Richman]: That is a good question. I track all my food in My Fitness Pal, me and like 25 million other people or something. It has got every food – you know, if you travel to China there is like the fast food chains that are in there too. It is sort of like every possible food.

[Damien Blenkinsopp]: So are you taking photos? Or how are you doing that?

[Jessica Richman]: No, I just enter everything.

[Damien Blenkinsopp]: Have you got a special app or anything that you like?

[Jessica Richman]: I use my fitness pal, which is the most popular one. I am probably in there six times a day logging everything I eat. And then I also do lots of little experiments with myself in terms of how much protein I am eating, how much fat I am eating, and I just started using [keto sticks 00:49:22] recently, and I had never used those before.

[Damien Blenkinsopp]: Yeah, oh, I just got – do you know the ketonics? I just did an interview, the last interview, but anyway the ketonics allow a slightly better correlated – because it measures your breath which is more correlated with the blood levels.

[Jessica Richman]: Awesome – I was looking at the blood kits also and they have those.

[Damien Blenkinsopp]: They are very expensive.

[Jessica Richman]: Yeah, they are very expensive. maybe that could be a business expense, I don’t know. Anyways, I am starting with the sticks and just sort of sampling and seeing how it can correlate how I feel with ketosis. If I feel warm and tired, then that is probably because I –

[Damien Blenkinsopp]: Are you going to be trying intermittent fasting or anything like that?

[Jessica Richman]: I might. I gained the startup 30 so I think I am trying various things. So we will see, intermittent fasting is really interesting and I don’t think I will do the warrior diet because that is the one where you eat once a day and I feel like I would just sort of keel over. But it is really interesting and I like that our users are generally people who are interested in these kinds of things and I like that we can bond over our various weird potions that we are eating and trackign about ourselves.

[Damien Blenkinsopp]: So what has been the biggest insight that you have learned about your biology through doing some kind of tracking or –

[Jessica Richman]: That is a good question. That is a really good question. I think in terms of the microbiome, I think I have sort of – my cofounder is a lifelong vegetarian who has never eaten meat in his entire life. And his parents were vegetarians and he hasn’t eaten meat. So his microbiome is very different than mine because I have sort of been an omnivore my whole life and it is really interesting to see the differences between people who share a lot of environments in common but eating very different foods, so I think that was a really interesting insight. As far as tracking myself over time, I think I am lucky and that I don’t have a health condition that sort of gives me an unusual microbiome. Mine is very normal so that hasn’t really shown up very much in the things that I am doing. I am tracking a lot of these dietary changes, which I just started doing, so we will see how they go.

[Damien Blenkinsopp]: Well, that is a good point you bring up. Someone could have a microbiome done and then if they fit straight in the middle of the road, then it is probably not a bad thing.

[Jessica Richman]: Exactly, it is a very good thing.

[Damien Blenkinsopp]: It also just depends on how extreme the experiments you are doing on yourself are.

[Jessica Richman]: Right, exactly. And I think I am just sort of dipping my toe in the water of cool things people can do to track their health, but there are definitely users who do much more interesting things and sort of want to see the effects of them.

[Damien Blenkinsopp]: Right, so what would be your number one recommendation to someone trying to use some form of data to make a better decision about their body’s health and performance?

[Jessica Richman]: I think there is sort of advanced versus not advanced. So I think the very basic thing is tracking what your food and exercise, it really changes your behavior dramatically. And I have noticed this and it is a very obvious thing and advanced quantified self people are going to be like, ‘Ha ha, I have been doing that for 20 years.’ But for the average person I think it really makes a big difference because you just start seeing – you don’t want to eat junky food when you know you are going to record it. And you start seeing how good you feel when you eat certain foods versus other ones and I think it is really motivating and it is really disciplining.

So I think that is sort of the basic recommendation. I think advanced recommendation is sort of don’t be afraid of scientific literature. Working with scientists and as a scientist, you see what goes into scientific research and you see that it is this really messy field where people are trying different things and sometimes they work and sometimes they can’t be reproduced. So don’t be afraid to delve into literature and see what is there for you and then try to make it work for you. And don’t sort of take it as received wisdom, that it has to be exactly right.

[Damien Blenkinsopp]: Yeah, that is a great point. Thank you, both of those are great point like the psychological benefits and accountability. I think that is probably one of the biggest things that is happening right now with all the devices and everything, just reinforcing behvaiors.

[Jessica Richman]: Yeah, I think it can’t hurt and it takes a little bit of attention, but I think it is attention well spent because it helps people learn to track themselves better and learn to understand what is going on when they feel a certain way, what is likely to be causing it. And I think it is really beneficial.

[Damien Blenkinsopp]: Jessica, thank you so much for your time today. I know you are very, very busy at the moment so it has been great that you have made the time for the show.

[Jessica Richman]: This was so fun, I am so glad. Thanks for taking the time to talk with me. This is really great.

[Damien Blenkinsopp]: Thank you very much.

[Jessica Richman]: Awesome, I will talk to you later. Bye.


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