THE MICROBIOME SUMMIT : The New Path to Health

The American Gut Project

Dr. Daniel McDonald, PhD

dr-daniel-mcdonald-phd

Dr. Daniel McDonald, PhD

American Gut Project

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Overview

Founded in 2012, The American Gut Project is a crowd-sourced and crowd-funded project that is considered “citizen science.” It allows anyone to participate, and all data collected is a part of public domain. At this time, The American Gut Project has received samples from individuals from 45 different countries. In this interview with Dr. Daniel McDonald, the scientific director of The American Gut Project, you will learn about some of the major findings so far: the number of types of plants that people consume has more of an effect on microbiome diversity than being a vegan or omnivore; there are more microbial differences between people in different countries than in different areas of the same country, lack of sleep and alcohol can contribute to a reduction in microbial diversity, and our microbiome changes as we age – by the time we reach 3 years of age, our microbial population looks like that of an adult!

Transcript

  • Tracey:
  • So, we’re here today with Dr. Daniel McDonald. He is the Scientific Director of the American Gut Project. Welcome, Daniel.
  • Daniel:
  • Thank you. I’m excited to be here.
  • Tracey:
  • Can you tell us what is the American Gut Project and how did it all begin?
  • Daniel:
  • The American Gut Project is a crowd source, crowd funded project where our goal is to bring microbiome research out to the general public and allow anybody to participate in what we think is a very fun and exciting new area of research. The American Gut Project came about from a conversation that professor Rob Knight and Dr. Jeff Leach had about how we can allow people around the world to take part in the research that the National Institutes of Health here in the United States has deemed quite important as is evidence by the human microbiome project where they invested $173 million dollars.
  • Tracey:
  • Right, and these two individuals, they are really the pioneers in this area of medicine?
  • Daniel:
  • Rob Knight in particular has really been leading the charge, as are many other individuals in the microbiome field, but Rob has been tied into this since everything really began to kick-off back in the middle of the 2000s. But, there’s many other notable members as well too who have done incredible
    work, including people like Jeff Gordon, Cathy Lozupone and many others.
  • Tracey:
  • Yeah, for sure. For sure, can you tell us what your role is at American Gut?
  • Daniel:
  • Absolutely. I’ve been involved since the project started in November of 2012, and this actually forms a cornerstone of my dissertation which was on the development of a microbiome reference database that stands thousands of individuals. So, really The American Gut Project has been a critical component
    of my work over the last few years. At this time, as a scientific director, what I’m attempting to do is find new ways we can steer the project and in particular, how we can engage with different populations that are not currently well represented in our reference database.
  • Tracey:
  • Daniel, can you describe to us the size and scope of this project and what kind of diseases that you are looking to catalogue?
  • Daniel:
  • Absolutely, so at this point, we have received samples from participants from around 45 different countries. Most of those countries that are represented, we only have a handful of samples from. But in total, we’ve received on the order of about 15,000 samples of participants so far and we’re really eager to continue to expand that even further. Most of our samples come from North American at this time but we do have about 2,500 to 3,000 that have come in from the United Kingdom and hundreds that have come in from Australia through strategic collaborations that we have established. In terms of the diseases that we want to categorize, we really want quite literally, everything. So, there’s been a lot of exciting research that have suggested relationships with the microbiome and a wide number of diseases including obesity all the way through to autism and Parkinson’s disorder and the reality is that we
    suspect that there are other types of relationships between disease and the microbiome that are yet to be discovered. And so, by casting a very wide net and getting a very large number of samples, we’re hoping to detect a further and more subtle signals that we can use to generate hypotheses and follow up with funding agencies such as the National Institutes of Health, for more targeted and rigorous research efforts.
  • Tracey:
  • Would you highlight for us what the project is and what the project is not? Just to give us a very clear understanding.
  • Daniel:
  • Absolutely, and this is actually a fairly common question that we get from different types of participants. So, a lot of individuals are hoping at this point that you know, from a microbiome sample, we might be able to provide some type of dietary advice or some type of medical advice. We cannot do that with the
    American Gut Project. This project is purely research based and we cannot provide advice from a contribution to this effort. However, what we can do with your sample is integrate it into the broader reference database of microbial configurations that we’ve observed to be associated with humans.
    We can use this as a backdrop to better understand other microbiome studies that are going on, to help to detect whether there are subtle microbial configuration signals that are contributing perhaps to disease or at least correlated with disease and lead to follow-up questions that we can hopefully
    answer.
  • Tracey:
  • Daniel can you explain to us who and where all your collaborators are that are going to be using this information collected?
  • Daniel:
  • Yes, so we actually don’t know everybody who is using these data because what we do is with all of the data that we generate and the questionnaire responses, we deposit them in a de-identified fashion into the public domain. So, at this point, all of the sequence data for the American Gut are just freely
    available for anybody to use. Within the project itself though, for our ongoing research efforts, we’ve been working with over 150 different individuals and some of these groups are focused on say biogeographical signals that might be present in the data, particularly Professor Katherine Pollard and Professor Jessica Green. They’ve been very interested in leading the charge there. And then, Jessica — our professor Jessica Metcalf at Colorado State University, has been very interested in the relationship between industrialised and non- industrialised individuals and what type of microbial signals might be
    present there. But in general, we also — because we don’t know what type of signals we’re looking for, the questions that we ask are really quite broad in our primary survey. And then, we have follow-up questions such as a picture based, validated food frequency questionnaire which allows us to get very
    detailed characteristics about an individual’s diet. We actually also have a surfer microbiome survey that individuals can take. There’s a graduate student in one of our collaborating labs, the Dorrestein Lab here at UCSD who is absolutely in love with surfing and he’s been able to grab a hold of that for his
    own research projects. And basically, what he’s trying to do is from surfers all over the world, he wants to get a whole bunch of skin samples coming in to see what type of relationships the ocean may have on the skin microbes associated with those individuals.
  • Tracey:
  • Right, so interesting! Daniel, this is considered a citizen-science project. Can you tell us how many samples do you want us citizens to give up?
  • Daniel:
  • I would be very excited to have our freezers full of millions or tens of millions of samples to be quite honest. You know, getting there is going to be a bit of a challenge. And, one of the ways we’re trying to figure out how to get as many people involved in the project or enable as many people to take part in the project, is by working with collaborators in different countries to provide local
    gut project efforts.
  • Tracey:
  • Right, interesting. So, you want Canadian samples?
  • Daniel:
  • Absolutely, absolutely. We’re in discussions as well too about how to improve the process for Canadians as well through some collaborations at different universities. But we haven’t figured out all the pieces of that puzzle yet. So, one thing I think I forgot to mention as well too is that the way that individuals can participate is through our partner at fundraiser.com and that’s where the contributions to the project actually occur. So, Fundraiser is a very broad citizen science-oriented website that actually allows these crowd funded projects to be possible.
  • Tracey:
  • Right, Daniel would you mind elaborating on some of the specific diseases you might be looking for when you’re putting out your call for samples of stool and skin samples?
  • Daniel:
  • We’re interested really in literally everything. So, we have some researchers that we’ve been working with who are, for instance, interested in atopic dermatitis or eczema, for instance. And getting skin samples associated with those types of skin lesions can be quite interesting and there’s actually been
    some very exciting microbiome research separate from the American Gut Project looking at differences in microbiome communities associated with those types of skin disorders. And then, on the — we’re also quite interested in neurological diseases as well too. So, we actually have a sub-project within the
    American Gut looking at the autism spectrum disorder diseases. And, we’re really hoping to get a lot of samples from individuals who are on the spectrum as well as any siblings they might have as well too which can be used as a balancing point to help understand the individual who is affected, whether
    there are differences in the microbiome communities. And then of course, we’re quite interested in metabolic disorders such as diabetes type I and type II, obesity, inflammatory bowel disease, Crohn’s disease. We’re really interested in basically everything. We have attempted to structure our questionnaire to be able to characterize a wide number of different types of diseases as well as to
    allow for the distinction between whether the diagnosis an individual might have is a medical diagnosis or something they’ve self-diagnosed. One of the ones I think that’s going to begin to get very exciting as well too or different types of depressions as well. So, as I understand it, many different types of depressive disorders have been observed to be associated with gastrointestinal inflammation, gastrointestinal distress and we are beginning to see some signals that suggest, at least a correlative relationship between the microbiome and say, major depressive disorder. And, this is something that
    other groups around the world have also begun to observe. So, I’m very interested in continuing to expand out those sample collections.
  • Tracey:
  • So, if I’m to understand this correctly, the more samples you have, the faster you can get to answering all of the questions that you have?
  • Daniel:
  • That is absolutely the case. I mean, this is a big, big, big unknown right now. But, as we get more samples, subtle signals begin to be possible to detect and then we can use this, for instance, as pilot – or literally anybody in the world can use this as pilot data – for a more focused research grant they can target to an appropriate funding agency. So, really you know dig deep on any of these questions.
  • Tracey:
  • Right, it’s incredible that this is — this project is so collaborative. I really haven’t heard of another project like this.
  • Daniel:
  • There is actually one, it’s called the Earth Microbiome Project which the American Gut is actually a sub-project of. So, the Earth Microbiome Project was founded by Rob Knight, Jack Gilbert and Janet Jansen. We recently published this back in — in nature and in early November and that was a project that spans I think 100, or 150 different labs from around the world and brought together samples from every conceivable environment. But, to be honest, I think the microbiome field, one of the hallmarks of it is that it tends to be very collaborative in nature and really brings people together, and one of the needs
    for this is that we have to have a lot of different disciplines to understand what’s going on. So, within Rob Knight’s lab just by itself, I mean we have a computer scientist which is entirely my background and we actually have multiple computer scientists. We have biochemists. We have statisticians. We have molecular biologists. We actually have a dentist and a lawyer. I mean, we really try to bring together as many different groups as possible to make heads and tails of the data. And, that’s just scratching the surface in the number of types of disciplines that we work with.
  • Tracey:
  • What have you discovered so far at the American Gut Project?
  • Daniel:
  • Well, first we’ve discovered that there’s a lot of people who are very interested in sending us their poop which has, you know been a fun experience in and of itself. But from taking a look at the data that we’ve collected so far, one of the really interesting things that’s fallen out from this is, when we ask people about what they self-describe as their diet type, say vegan or vegetarian or omnivore, we actually don’t see a really big effect in the different types of microbiome configurations in the data. However, we have a different question that we ask which is the number of types of plants that people report as eating in a given week and so, this is you know, really the diversity of the plants that they’re consuming. And, we see quite a strong effect with that question which was really quite surprising to us. We did not expect to see that. And, going to the validated food-frequency questionnaire that we ask that some individuals have taken, you know we also see that this question is highly correlated you know, of course, with different types of fibre that are in their diet and different types of microbes and macronutrients which makes sense. But perhaps, to me, one of the things that was really surprising was I would assume that vegans would have a very different microbiome configuration but we don’t actually see it. And it could be that you know, how a vegan chooses to eat can be quite different from individuals because you know, you can eat a lot of French fries for instance while still being vegan. So, I was — we’re still exploring this a bit. But, we did take, relatively recently, a set of the samples that were from
    individuals who didn’t eat many plants per week and those who ate a lot of plants per week. And when beginning to take a look at the small molecules that are present in those samples through a collaboration here at with the Dorrestein Lab and their expertise is really on the investigation
    of these small little molecules and these are things like the by-products that the microbes might produce and it’s really the communication between the individual microbial cells and the microbiome with the host. So, we’re beginning to dig down and see what type of differences actually exist in these microbiome communities based off of this plant difference. We’re also observing things like having — the amount of sleep that individuals self-report as having an impact on their microbial diversity as well too. And, I can’t say you know, whether say having more sleep leads to a better microbiome. You know, that’s a really difficult question to get to, but it does appear that the amount of sleep that people get does lead to differences or at least correlated with differences in their microbiome. And, specifically
    individuals who self-report as getting less sleep appear to have less diversity. So, if you think of diversity in terms of like an ecological context like a forest, you might assume that a more diverse forest is a healthier and more resilient forest, whereas one that is not nearly as diverse, might not be as healthy. I
    wouldn’t go as far as saying that that’s definitely the case with microbiomes that you want a more diverse sample, but it does appear for instances with things like sleep, that it does impact, or at least is correlated with the amount of diversity that’s in the sample.
  • Tracey:
  • Right, interesting. Any other lifestyle factors?
  • Daniel:
  • We are observing relationships similar to sleep with alcohol. We’re beginning to observe some relationships in the data with — and this is not lifestyle factor – but with depression which is one of the reasons I’m very interested in getting in more samples from individuals who have some type of depressive disorder so they can begin to understand this further. We’re seeing associations by country
    that people are coming from. So, individuals in the United Kingdom and the United States look to be quite different. Where individuals in the United Kingdom actually have a higher median diversity than those in the United States which is surprising because they’re both western countries and the diet have a fair bit of overlap, not necessarily the same of course but a fair bit of overlap. And so, we were really surprised to see this — what appeared to be an elevated amount of diversity between the countries. And, we’re not entirely sure why. Oddly, we do not appear to observe a biogeographical signal within
    the United States so you might think that say individuals living on the left coast have some type of differences than individuals in the right coast – or the east coast – given that the — we observe a difference between the United Kingdom and the US. But so far, we haven’t actually been able to detect a significantsignal between the coasts.
  • Tracey:
  • About — have you noted any differences between — the microbiomes between the young and old?
  • Daniel:
  • Oh, absolutely, and, that’s a fairly strong signal in the data and this is something that’s been replicated in a few other studies as well too. Infants for instance tend to look very different than adults. And then, at around the age of 3 or so, they tend to much more resemble an adult population. But, we do observe a change in the microbial communities over different generations and different, I guess, decades of life. And, there’s of course the possibility — there’s a lot of possible reasons I should say for why we might be observing a different microbial signal. It might not be the age of the individual, it could have been say some early life factors that were going on and there’s definitely environmental exposures and different products that we’re exposed to at different stages in our lives and you know, common products you saw in the grocery store in the 80’s are not necessarily the same type of products you observe in a grocery store in the 2000’s. But, what we can say is that it does appear to be a strong correlation between the age of the individual and the types of microbial configurations that they do have.
  • Tracey:
  • What about medication use? Like antibiotics?
  • Daniel:
  • It’s a great question. So, characterising the type — this very specific type of medication that people take is really difficult in a very big project like this and that’s one that we — to be honest, struggled a bit with. But we do ask a very basic question about recent antibiotic history so you know, have you taken antibiotics in the past week or the past month, past six months or past year, irrespective of the antibiotic. We do observe some quite strong effects and particular with those who have taken antibiotics in the past week. They’re quite different from those who have not taken them in the past year. But, we see a significant signal and a variety of different ways. Even out to individuals who have not taken antibiotics or have taken antibiotics in the last six months. So, there does appear to be some type of persistent effect that can last quite a bit. And, it’s actually a fairly common question that I get from individuals, they’ll contact us and say, “Hey you know, I just took antibiotics. Should I hold off and not provide a sample?” And, you know like it says, we’ve very interested in samples from everybody at every stage of their life, irrespective of any type of medication regime they’re going through, or anything to be quite honest.
  • Tracey:
  • Right, fantastic. Thank you so much, Daniel.
  • Daniel:
  • This has been fun.