I’m really excited to have a special guest, Jeff Leach from the American Gut Project, on this episode. We talk all about the gut, which is, of course, one of my favorite topics.

In this episode, we cover:

1:00 What is the American Gut Project?

4:30 How the study of our microbiome changes as technology advances

15:22 Surprising insights from the latest gut bacteria research

22:38 What effect does diet have on the microbiota?

29:22 The effect of VLC/ketogenic diets on the microbiota

45:18 How people can get involved in the American Gut Project

To join Jeff’s American Gut Project: http://humanfoodproject.com/americangut/

Full Text Transcript:

Steve Wright: Hey, everyone. Welcome to another episode of the Revolution Health Radio Show. This show is brought to you by ChrisKresser.com. I’m your host, Steve Wright from SCDLifestyle.com, and with me is integrative medical practitioner and healthy skeptic Chris Kresser. Chris, how’s your day going?

Chris Kresser: It’s going great, Steve. How are you?

Steve Wright: I’m having a good day, too. Boulder is having some good weather, and as long as my computer doesn’t blow up, this is going to be a great podcast.

Chris Kresser: Good. Well, I’m really excited. We have a special guest here today, Jeff Leach from the American Gut Project, and I’m just going to ask Jeff to introduce himself, tell us a little bit about his background and what he’s up to, and then we’re going to talk all about the gut, which is, of course, one of my favorite topics, and I know it’s one of yours, too.

Jeff Leach: Hey, Chris and Steve. Thanks for having me on!

Chris Kresser: Hey, Jeff.

Jeff Leach: You guys hear me OK?

Chris Kresser: Yeah, we’re good.

Jeff Leach: OK.

What Is the American Gut Project?

Chris Kresser: So, Jeff, maybe you could just tell us a little bit about your current position, what you’re up to, what your background is, and we’ll go from there.

Jeff Leach: OK, great. I’ve actually been doing archeology since the early ’90s, kind of a mixture of archeology and anthropology. I was interested in diet from an evolutionary perspective, which kind of led me to the gut. About 8 or 10 years ago I started getting interested in the gut microbiome, and of course, that’s pretty much when it started taking off, when next-generation sequencing starting showing up and it really started to burgeon. There weren’t a lot of people thinking about the gut and the dietary influence from an evolutionary perspective, so I thought I could play a role there and make a contribution. So, in the last couple years I’ve really gotten involved in gut microbiome research. I’ve actually gone back to school, now pursuing a different degree in medical microbiology at the London School of Hygiene and Tropical Medicine, and I collaborate with a number of researchers now. We have ongoing projects in Africa looking at hunter-gatherer populations, and then, of course, I helped co-found or came up with the American Gut Project that we’ve now launched, and that is up and running.

Chris Kresser: Wow, that sounds fascinating, Jeff. Can you tell us a little bit more about the American Gut Project, what its goals are, and where you’re at with it right now?

Jeff Leach: OK. Yeah, the American Gut Project we kind of dreamed up last summer, Rob Knight and I. Rob’s at the University of Colorado at Boulder. He’s a world-leading bioinformatics guys, and he’s just about on every other microbiome paper that comes out, it seems, lately. But Rob and I got to talking, and one of the things that was missing was a huge sample of human beings, you know, 5, 10, 15 thousand people. In order to do that project, it would take hundreds of millions of dollars and years to put together, so we decided we would pursue something this through crowdfunding or crowdsourcing. So, we put together the project on paper, if you will, last summer, and then we approached the University of Colorado at Boulder for ethics approval to do the project. So, we spent a couple of months getting IRB, or institutional review board, approval for the project, got that in place, and then we launched it on a crowdfunding site. And so, as of today, we’ve got about 7000 people enrolled in the project. It’s the largest microbiome project in history. Our goal is about 20,000. We just released data on our first 1000 individual participants, and the long-term goal is, are there patterns among the general population based on diet and lifestyle that may be interesting? So, for example, are vegetarians different than omnivores? Are people with large BMIs different than people with small BMIs? Does the number of people in your household matter? Do you live in the country or the city? Does that matter? So, putting all that metadata together with the actual sequencing results – because we send you a kit to your house where you can self-sample and send it back to us for a $99 donation – are there any patterns with that metadata? We just started getting the initial data in, so we’re pretty excited about what we’re seeing so far, and we think it’s going to get interesting once we get up around 5, 10, or 15 thousand samples.

How the Study of Our Microbiome Changes as Technology Advances

Chris Kresser: Right. You mentioned earlier that DNA PCR analysis has really changed the study of the microbiome and particularly in the gut, so tell us a little more about that.

Jeff Leach: Yeah. If everyone remembers back a decade or more ago, or back two decades, when they sequenced the human genome, it cost hundreds of millions, if not billions, of dollars to do. So, what’s happened with next-generation sequencing, it’s almost like technology with cameras. The pixels have gotten better, the computing power has gotten better on laptops, and the same thing has happened in the laboratory. You can literally take a poo sample from somebody and take a snapshot, if you will, of the DNA of the bacteria for literally just a few dollars. You know, 5 or 10 years ago that would’ve been hundreds of thousands of dollars, so next-generation sequencing has dropped the cost and brought the cost down, and then the analytical tools have gotten a lot better as well, the bioinformatics have gotten a lot smarter, if you will, and cloud computing and big data has gotten a lot easier. So, it’s kind of a meeting of big data, big analysis, and technology getting cheaper that makes this all possible.

Chris Kresser: Mm-hmm. Let’s talk a little bit more now about what the significance of all of this is because I know for some people who have been listening for a while to the show, they’re aware of the connection between the microbiota and the gut and various aspects of human health, but for some people who might be a little newer, this is, perhaps, news. Interestingly enough, I saw a study today in Nature – or a report on the study, at least. I’m not sure if you saw it, Jeff. Some Japanese researchers found that butyrate, which is a compound that’s produced by bacteria fermenting dietary fiber in the gut, can actually improve T regulatory cell production. T regulatory cells help keep the immune system in balance, and a lot of people with autoimmune disease have impaired T regulatory cell function. Essentially the study is showing that the gut bacteria can directly influence the immune system. We’ve known for a while that butyrate, this compound, had an anti-inflammatory effect, but this study showed a particular mechanism for how it does that. This is just one example of many, many studies now, it seems, Jeff, that are showing a connection between our gut bacteria and aspects of health, which we may not have even realized would be related to our gut, like our mood, depression, skin, etc. Is this something you’re following a lot, the research around this?

Jeff Leach: Oh, yeah. What’s interesting about this, as you know, Chris, and anybody who follows this subject, it wasn’t that long ago, just 5 or 10 years ago, before we started realizing – you’ve heard the number repeated before – 90% of the cells in the human body are not even human; they’re microbial.

Chris Kresser: Mm-hmm.

Jeff Leach: We’re more microbe than mammal. That really wasn’t well understood a decade ago, and so the new DNA techniques are allowing that. And what’s really remarkable is that not since Darwin’s concept of natural selection has something had such a profound impact on our understanding of “self.” In our anthropocentric world, we think we’re the center of it all, but at the end of the day, the microbes are actually pulling the levers on a lot of what’s going on when you consider that at the gene level they outnumber us 150 to 300 to 1. We’re born with genes that mom and dad gave us, and we’re pretty much stuck with those, but the genes in our gut – again, the bacteria are called the microbiota, and when you add their genes in as well, that’s our microbiome. Of course, a biome is just an ecosystem, so we have this inner ecosystem. So, depending on how we treat them, they can make life OK or they can make it problematic, and when they get out of balance, it’s now thought that that may be the root or the cause of a lot of disease. The problem is working out causality versus correlation

Chris Kresser: Right.

Jeff Leach: People’s general take on bacteria, which is still kind of a little bit of a hangover from the last 50 years, is that bacteria are bad, so we need to kill them through antimicrobial soaps and antibiotics, which, of course, save lots of lives, and on and on and on. We’ve improved hygiene and sanitation and really changed things, but the other edge of that sword is that we may be changing the relationship of the microbes in such a way that this imbalance is a precursor or we’ve opened the pathogen’s door, if you will, to inflammation. Now, as you clearly know, Chris, it’s hard to be in the medical sciences now and not be thinking about how bacteria affect your particular field of study. It doesn’t matter if it’s psychiatry. It doesn’t matter if you’re a heart surgeon or if you deal with autoimmune disease. Microbes are in there somewhere, and so now what everybody’s trying to do is to figure out what role microbes play in diseases as diverse as autoimmune diseases or obesity or other metabolic disorders like type 2 diabetes. But again, it’s the early days and most microbiome researchers will tell you that. They’re very cautious. They don’t want to make the same mistakes that… I wouldn’t call them mistakes, but they don’t want to overpromise, if you will.

Chris Kresser: Yeah.

Jeff Leach: Back in the ’90s, we were all told that if only we could sequence the human genome, within a few years we could unravel disease, and of course, that really hasn’t come to fruition. And microbiome researchers are also very cautious about dietary suggestions to nudge your microbiome because everybody’s worried about how one day butter’s good, the next day butter’s bad. Carbohydrates are good one decade, carbohydrates are possibly bad the next decade. So, microbiome researchers have really paid attention to what has happened to the genomics crowd with the human genome, and they’re very hypersensitive to the ebb and flow of nutrition advice, so that’s why you very seldom will hear microbiome researchers kind of go out on a limb and tell you what they really think.

Chris Kresser: OK. Well, I’ll try not to put you on the spot too much!

Jeff Leach: That was a way of setting up your next question!

Chris Kresser: Yeah, well, I may try to tease a few things out of you in a very noncommittal way, but there are a couple things you said that I just want to go back to. This is one of my favorite topics, and we could talk forever, but there’s a quote that I actually have in my book from Justin Sonnenburg at Stanford that says something to the effect of humans are just elaborate vessels for the propagation of microorganisms.

Jeff Leach: Yeah, spot on.

Chris Kresser: I thought that was a fantastic quote and really does change our whole concept of self and identity. And when you really start thinking about it, of course, it can be a little creepy, but the upside, in my opinion as a clinician, is what you mentioned: The genes that we inherit from our parents of origin are set, and certainly there are environmental triggers and epigenetics to consider, but the genes that we have in our microbiota are somewhat mutable. We don’t really know how much yet, of course, but as a case in point, in that paper that I just mentioned in Nature, what they found is that the bacteria that ferment the fiber and produce butyrate, that causes epigenetic changes that regulate the expression of genes that are responsible for the differentiation of T cells. And so, it’s the gut microbiota effecting epigenetic changes in gene expression in our body, which have real and lasting effects on our health. So, it’s a pretty exciting time to be involved in this area and even, as a clinician, for me on outside just following the research but starting to apply that in my own patient population and seeing some pretty dramatic results just from modulating the gut flora.

Jeff Leach: Yeah, I think what’s interesting is that a lot of the initial studies over the first couple of years were basically kind of creating inventories of who’s there, what’s their relative abundance. And this originally started off with culturing; now there are noncultural techniques. We’re now moving from these catalogs of who’s there to what are they doing. It would be nice if you could pin down one species or one strain that’s causing this or causing that, but in most cases, it’s the consortium, it’s the community, and so isolating one or two strains may not get you to the solution that you’re after with regards to causality. I always kind of equate it to engineers who work on cars. You’ve seen the wind tunnels with all the white lab coat engineers, with the smoke running over the car like it’s going 100 miles an hour, and there’s a set of engineers that work on the door handle, a set of engineers that work on the aerodynamics of the mirror, the guys and ladies that work on the slope of the windshield, and each one of these things plays into the performance of the overall automobile. The question is, which ones are really more important than the other ones? There are keystone species or groups of bacteria that play a bigger role?

Chris Kresser: Mm-hmm.

Jeff Leach: And so, right now it’s figuring out all the engineering, if you will, of all the moving parts in the analogy being the car. In this case, it’s groups of bacteria, either phylum or species or strain level. And there are hundreds, if not thousands, of potential studies and things to consider, and each one is important, but now we need to kind of pull back and stare at it from a distance and see what really matters the most because if everybody gets a say in it, let’s say the bumper team has a say in it, and the windshield team has a say in it, what you’re going to end up with is lots of good advice from a thousand different people, but you couldn’t possibly keep up with it all. So, what are the big-picture things that the microbiome is trying to tell us – that’s the Holy Grail.

Surprising Insights from the Latest Gut Bacteria Research

Chris Kresser: Right. So, with your previous caveat in mind, what sort of things can you tell us in terms of major patterns or things you’ve observed, things that have surprised you in doing this work so far? We understand, of course, that it’s still early days and these aren’t hard and fast conclusions and that it may change in the future, but I’m just curious to know what general trends have become apparent, if any.

Jeff Leach: Yeah, that’s a great question, and I think it’s a question that’s asked every day. I guess from my perspective, if I can step back a little bit, the thing that struck me the most a few years ago when I really started getting involved in this was that if you look at all the studies, you have 10 obese patients who are sequestered in a hospital ward and they’re fed this diet and they collect their stool samples and they change their diet, or even the human microbiome project where you look at 250 healthy individuals with average BMI and average age of 25, in all these studies, including the ones in Europe and Japan and Australia, hundreds and hundreds of studies, the thing that’s striking about that is that potentially, most likely, every participant in the study is compromised, in that they grew up on a Western diet.

Chris Kresser: Right.

Jeff Leach: We all take too many antibiotics. We all drink too much tequila. We all do these things to our body. We drink water that flows through a public water supply that has things in it that are supposed to neutralize bugs.

Chris Kresser: Yeah.

Jeff Leach: And so, when we’re trying to get to that fountain of microbial balance or optimal microbiome, we’re never going to get there looking at Western populations because we’re all compromised. The thing that was most striking to me was there was no data on populations that hadn’t taken antibiotics, that hadn’t wolfed down a Big Mac and Cheese, that hadn’t been drinking tequila, so that’s when I, a few years ago, said we need to look at ancestral populations, and they’re disappearing very quickly. So, Maria Dominguez-Bello at New York University was doing work in South America, her and Marty Blaser. The Gordon Lab was doing a little bit of work in Malawi, but they’re still looking at rural populations, which are basically just poor folks living in cinderblock houses and sheet metal homes that are barely squeaking out a living, and those really aren’t ancestral populations. Their diet, in a lot of cases, is, like in Burkina Faso and South Africa, 50%, 60%, 70% of their calories come from grains. That’s why we turned to South Africa, spent some time in Namibia and Botswana looking for these ancestral populations among the San Bushmen. Of course, they’ve been fully acculturated and resettled now, so now we’re in Tanzania working with the Hadza, which are a perfect referent for what we’re after. So, that was the most striking thing to me, is missing that baseline population of what a group might look like before the antibiotics and so on and so forth.

To kind of get back to your question, the one thing that you see and that we’re starting to see in American Gut and that you see in other large studies is that everybody kind of falls along a continuum. A few years ago, it was thought that if you had a high level of Firmicutes, which is a phylum of bacteria, that it was more predictive of maybe an obese phenotype, and if you had less Firmicutes, you were more likely to be lean, but that turned out not to be true. When you look at the Human Microbiome Project – and again, that’s a healthy group of people with an average age, I think, in their 20s – you had some people who had 80% Firmicutes and 20% Bacteroidetes, and then on the other end you had some people who had 20% Firmicutes and 80% Bacteroidetes. In other words, everybody kind of falls along this continuum. And then there was that idea that you could divide everybody up on Earth into these groups or these enterotypes, which turns out is not true either. Enterotypes, everybody kind of falls along a continuum. So, one of the most breathtaking things is that there is no patterning, at least based on the questions and the metadata and the populations that have been looked at so far.

Now again, this is separate from looking at certain diseased groups or dietary interventions. Those are separate. But when you kind of lump everybody together like we’re doing in American Gut, there are some early patterns that are popping out, but you’re not getting striking patterns that most people think exist. I think that has a lot to do with the environment as a great equalizer. Diet is only one piece of the formula. Lifestyle is a big component, and again, we see that in hunter-gatherers. Like, in Tanzania we see that men eat much more protein and fat than women, and women eat a lot more fiber and probably resistant starch, so it will be really interesting to see if their microbiomes are different. When we look in the United States, when we look at 1000 men and women in the American Gut Project, they look pretty much the same at the phylum level. There are the same number of Firmicutes, the same number of Bacteroidetes, so there’s no separation between men and women yet. Evolution teaches us that more than likely men probably did consume more protein and fat than women if the Hadza are a good referent, and so we should expect, based on diet, that we should see some differences, but I think what is going to happen is that the environment is the great equalizer. The fact that you share the same water, share the same soil, you’re covered in the same feces and blood of the animals that you consume and the dirt from the plants you dig. I think that ultimately levels the playing field, and that social interaction and that movement of bacteria is very fluid between individuals, the soil, the plants, and especially the animals. So, it’ll be really interesting to see how that shakes out.

But to kind of get to what you’re really asking, is one diet more interesting that another with regards to promoting a healthier microbiome, and the question then goes back to, what’s a healthy microbiome? Because we don’t know – there are some ideas, but we don’t know – we don’t know which direction you should be nudged. Again, that’s why I think these hunter-gatherer populations are important. We know that people who eat lots of whole grains seem to have high levels of a group of bacteria called Prevotella. We see that in Burkina Faso. We see it in South Africa. We see it in a few other places. And then you have people like Michael Pollan, kind of who is the Omnivore in Chief, who have super high levels of Prevotella. But then we find out that Prevotella is associated with HIV, it’s associated with rheumatoid arthritis, it’s associated with kids who have autism, and it seems to be associated with inflammation, yet you have somebody like Michael Pollan who has high levels of Prevotella that appear to be associated with whole grain consumption. Do we really want high levels of Prevotella if it’s been associated with these inflammatory states? And the answer is we just don’t know.

Chris Kresser: Sure. It’s hard to piece out correlation and causation there.

Jeff Leach: Yeah.

Chris Kresser: And the influence of other factors, definitely.

Jeff Leach: Oh, yeah. It’s endless.

What Effect Does Diet Have on the Microbiota?

Chris Kresser: So, grains and Prevotella. I definitely had heard of that, and I wrote about it a little bit back with the whole TAMO red meat controversy when that came out. I’m curious, Jeff, is there any research or any observations on your part about how different types of fiber trigger different types of growth in the microbiota, for example, soluble fiber versus resistant starch? Is eating fruits and vegetables sufficient? Do people need more soluble fiber, like in the form of starchy tubers or resistant starch, which would be a whole different category since it’s not really that prevalent in a normal diet? I know it’s sort of peripheral to your work in terms of getting this granular, but I’m just curious if you have thoughts about that.

Jeff Leach: Yeah, the most interesting group doing work on fiber is probably Harry Flint’s group in Scotland. I actually consume a considerable amount of fiber, I personally eat between 50 and 150 grams of fiber a day. I try to consume 20 to 30 species of plants a week if I can. So, I get a huge quantity and diversity. I’m interested in it because fiber is the primary substrate or food, if you will, for bacteria, so if you kind of look at it from an evolutionary perspective, if I was in charge of the USDA and Health and Human Services for a day – which God help us, I’m not… for a lot of reasons! – but if I was in charge of My Plate, which used to be the US Food Pyramid, I would argue that probably the most breathtaking change in the human diet that’s had the greatest impact on not only our microbiome, but our health, I would argue that that’s the drop in the diversity and quantity of dietary fiber. For example, you see in Africa 6-month-old Hadza kids that are being weaned onto food are getting 100 to 200 grams of dietary fiber a day, every day.

Chris Kresser: Wow.

Jeff Leach: And so, when you think about dietary fiber from the perspective of your gut microbiota, it’s food for them. You mentioned Justin. I know Justin very well. We’re doing some work with Justin’s lab. We’re actually taking hunter-gatherer poo and we’re humanizing mice with it, different bacteria from different seasons or different microbiomes from different seasons. And Justin will tell you that once you start starving your bacteria, you don’t deliver enough substrates, resistant starch and non-starch polysaccharides, when you don’t deliver enough of that stuff from plants, the bacteria have to eat something, so they start eating you.

Chris Kresser: Right.

Jeff Leach: They eat your mucous lining in your colon, and it’s thought that maybe once you start to degrade that protective barrier, you then expose it to potential problems. That’s interesting. Again, I pay a lot of attention to fiber for my own health, from my own perspective. For example, the most dominant bacteria in my gut are members of Ruminococcus. Ruminococcus are dominant genera in things like cows and rhinoceros, things that eat a lot of grass, and so I eat a lot of dietary fiber. I eat a lot of the whole plant. I always tell people if you’re going to eat asparagus, the best part of the asparagus is down at the bottom, and that’s the part we tend to cut off and throw away. We tend to think of that as stuff that kind of passes out the other end, but depending on your microbial makeup, as much as 60% or 70% of that can actually be broken down. If you don’t have a lot of, let’s say, Ruminococcus and these other guys in there, then a lot of that stuff will pass out the other end. So, when I go to the grocery store and I push the cart around, I look in the produce section. I say, OK, if you put Haagen-Dazs ice cream in your shopping cart, there’s not a lot of food for your bacteria there. There’s a lot of goodness for you, and we all like Haagen-Dazs ice cream, but when you put that bell pepper in your basket or that leek or that cassava or whatever it may be, I always look at it and say how much food in this is for me, and how much food is for my bacteria? That math is really simple. It’s how much dietary fiber and resistant starch is in here, and how am I going to prepare this? How I prepare the food has a dramatic impact on the microbiota as well.

So, I typically look at my grocery cart and make sure I feed my bacteria a diversity and quantity of dietary fiber, assuming I don’t have other issues that don’t allow me to do that. I don’t, so I try to maintain high levels of bacteria that degrade cellulose and pectin and lignin and things like that because when they do ferment, it produces short-chain fatty acids and organic acids, and we know they’re doing their job when we’re bumping and farting, OK? I tell everybody if you’re not having two to three bowel movements a day, then you need to go back and start over, and one of them should be a whopper. If you’re not having that kind of bowel activity, then you’re not fermenting enough – again, assuming you don’t have other issues – and so you need to increase the diversity and quantity of fiber. Why that’s important is when those bacteria ferment that dietary fiber – and again, get it from a lot of sources – it changes the pH of your colon. It makes it more acidic. A lot of opportunistic pathogens are pH sensitive, and so typically as those Ruminococcus and those Blautia and those Bifidobacterium and all those guys go up, you often see the other ones go down. It’s not always a one-for-one, but keeping your colon acidic through fermentation, frequent bowel habit, then all of that stuff leads to improved barrier function with regards to, you know, some people generically call it a leaky gut. You know a lot about it, Chris.

Chris Kresser: Mm-hmm.

Jeff Leach: With LPS translocating and a lot of other things like that. At the end of the day, I don’t think it’s rocket science. To borrow from Michael Pollan, eat food, mostly plants, not too much. I think that goes a lot way towards a healthier microbiome. And again, as you know, antibiotics are lifesaving, but we now know that they’re having a hell of an impact on our gut microbiota in a bad way.

The Effect of VLC/Ketogenic Diets on the Microbiota

Chris Kresser: Absolutely. So, Jeff, we’re now kind of getting closer to a subject that’s very controversial in the blogosphere lately, which is low carb, high carb, medium carb –

Jeff Leach: Right, right, right.

Chris Kresser: This whole debate. It’s getting kind of ridiculous, in my opinion.

Jeff Leach: Yeah.

Chris Kresser: What I’ve noticed – and these are just my observations as a clinician, and it’s a relatively small sample size – but almost every patient that walks in my door I do a comprehensive stool analysis, and I use different labs depending on what I’m looking for, but most of them report on the pH. They can give you an idea of what the pH is. They test for butyrate and total short-chain fatty acids and some other markers that give me an idea of what’s happening in terms of their consumption of fermentable fiber and the effects of that fiber on the gut flora. And what I’ve noticed is that many people who are on a ketogenic or very low carb diet – let’s say less than 30 or 40 grams of carbohydrate a day – come back with an alkaline pH in the stool. They have low levels of butyrate or other total short-chain fatty acids and some other markers of dysbiosis. So, that got me thinking and wondering about the potential adverse effects of a very low carb or ketogenic diet from the perspective of gut flora, gut microbiota, and wondering is it that people who are doing the ketogenic diets are not only doing a ketogenic diet, but they’re also just not eating enough plant fiber? And that kind of makes sense. If they’re really trying to limit their carbohydrates, they’re going to be somewhat limited in terms of the variety of vegetables and certainly fruits that they can eat. You can correct me if I’m wrong, but I think I read a blog post of yours a while back that was speculating maybe that 35 or 40 grams of carbohydrate may not be sufficient to reach the levels of bacterial fermentation that you were just talking about. Do you have any thoughts about that?

Jeff Leach: Yeah, it’s a great topic, and that’s interesting that you’re seeing the shifts in the pH in the colon. That’s fascinating, and it’s what you would expect. It’s an interesting topic, and it’s a pretty passionate crowd of people as well.

Chris Kresser: Oh, yeah!

Jeff Leach: Like Jimmy Moore and those guys. I mean, I have nothing but ultimate respect for Jimmy. He is all in, but I worry about it. What’s interesting in American Gut is we have quite a few paleo dieters that have identified as paleo dieters in the study, and we need a lot more. It’s a group of people we’re very interested in, and we’re interested in the very low carbohydrate guys as well. We’re seeing an increasing number of those guys in the study, but we need more of them to have any kind of definitive take on the problem. But if you just look at it from what we know from the literature – and there are not many studies that have isolated very low carb people – but when you come at it from the perspective of pH like you do, which is spot on, what happens when people go on a low carb diet – you know more about this than I do, but I always get the emails, What’s wrong with eating 10 cups of broccoli a day? One of the big things that the low carb diets do is they really drop out the resistant starch in the diet. And what’s interesting about a lot of butyrate producers, Roseburia and these guys and Eubacterium, they’re cross-feeders. For example, you have certain species of bacteria, groups of bacteria that break down whatever, cellulose and hemicellulose, and produce acetate and propionate and all these things, but a lot of the butyrate producers are cross-feeders and they’re feeding off of other activities. So, when I see a very low carb person, I often see not only a huge drop in dietary fiber, but a drop in diversity of dietary fiber and a significant drop in resistant starch, which is a huge source of nutrients for the microbiome as well. Resistant starch is often called the third dietary fiber.

Chris Kresser: Right.

Jeff Leach: But I lump it all together with anything that escapes digestion in the upper GI tract and ends up in your colon and is available for fermentation, and it’s a lot of things besides just dietary fiber. But I’m concerned about it for the exact reasons that you are. We don’t have the data. Nobody has done any nice clinical controlled trials, but when you starve the bacteria, you may see an increase in mucin degraders like Akkermansia and a few other ones. That shift in the pH is going to provide opportunities for pathogens to maybe bloom up that may cause some down-the-road, long-term problems. But again, maybe not. Nobody knows for sure, but if you’re shifting that pH and you’re not fermenting, you’re opening the pathogen’s door. It’s going to take a long time to unwind this, but I think the more low carb people we can get in the study, we can contribute to the conversation at least to the point where it can serve as a baseline for maybe more controlled clinical kinds of studies. But I would never recommend a low carb diet. I think you can eat lots and lots of healthy carbs and maintain your weight. I’m not necessarily a paleo dieter. I don’t eat grains. I have a type 1 diabetic daughter, so our family is very sensitive to the effects of all grains.

Chris Kresser: Sure.

Jeff Leach: And I don’t eat them a lot for that reason. I’m not really a strict paleo dieter because I eat legumes and I drink tequila. I’m giving it up!

Chris Kresser: That’s what I call the 80/20 rule, Jeff!

Jeff Leach: Yeah. The low carb thing is really terrifying to me from a microbiome perspective, but I want to couch that in saying that that’s not based on any data, so to speak. It’s just based on what we know about fermentation.

Chris Kresser: Mechanisms. Right.

Jeff Leach: Yeah, time will tell.

Chris Kresser: This is an interesting topic, too, from a clinical perspective because there are people who benefit from ketogenic diets and very low carb diets. For example, as you probably know, Jeff, there are several studies that suggest that ketogenic diets can be beneficial for people with neurological conditions, like Alzheimer’s and Parkinson’s, epilepsy, etc. And then some people who have type 2 diabetes and are extremely sensitive to glucose and have poor blood sugar control and insulin resistance, leptin resistant, and don’t do well with starch and foods that contain a lot of fermentable fiber often find themselves needing to follow a really low carb diet. In those situations, I’ve been, as a clinician, trying to figure out that assuming they’re going to stick with this really low carb diet, how can we mitigate some of the potential harm that could be caused to the gut microbiota? And again, we don’t know that it’s harmful, but I’m just speculating based on the same factors you just mentioned as well as some clinical data, like the stool testing that I mentioned before that. So, what I’ve been trying to do in those situations is get people who are doing a ketogenic or very low carb diet on some prebiotics and some resistant starch in the form of potato starch, which doesn’t seem to have any negative impact on their blood sugar and, in fact, actually has the opposite effect in many cases. Richard Nikoley over at Free the Animal has been writing a lot about resistant starch, and a lot of people with blood sugar issues have seen drops of, like, 10 or 15 mg/dL of their fasting blood sugar just from taking 4 tablespoons a day of potato starch, which has, as you know, a lot of resistant starch in it. And in my patients, I’ve seen a similar response and also with people with long-term constipation and gut issues. Of course, it makes sense that resistant starch could play a significant role there. So, I would say at least tentatively now that if anyone is on a ketogenic or very low carb diet, that you might consider some prebiotic fibers or resistant starch just to make sure that you’re feeding your gut bugs what they need to survive.

Jeff Leach: Right. I think it’s great advice. If I was stranded on a desert island for 10 days, what food would I take with me, assuming I had water? I would take onions, garlic, and leeks. It seems counterintuitive at some level, but as you know, the prebiotic concept, which was created by Glenn Gibson and Marcel Roberfroid in 1995, and I’ve published stuff with Glenn before on prebiotics from archeological stuff, but I eat onions every day. I try to eat leeks every day. Garlic not only keeps away vampires, but it contains prebiotic fructans. What’s interesting is – this is just a personal note – I have very high levels of Bifidobacterium because I consume lots of prebiotic foods, but I also don’t eat yogurt because it’s slimy and it’s nasty and I don’t like it, but I also don’t eat fermented foods either. I look at a lot of people who consume lots of fermented foods, and I have higher levels of lactobacillus than they do, and I don’t eat fermented foods. The bifidogenic effect of those prebiotic foods is well known. Elevating levels of Bifidobacterium, which is considered a helpful group of bacteria, can’t hurt. Now, at the end of the day, is Bifidobacterium going to save the day? Who knows? It’s a dominant bacterium in breastfed infants. It seems to decrease with age, but elevated levels of Bifidobacterium from prebiotics, it seems to also suppress some groups of Proteobacteria at the same time. It’s something that I’ve talked to Glenn Gibson about all the time at the University of Reading. He’s the world’s leading expert on prebiotics, and he’s probably published 500 papers on prebiotics.

Chris Kresser: Yeah. I’ve read lots of them.

Jeff Leach: Yeah, and Glenn’s a fantastic guy and he’s funny. And I think from a resistant starch standpoint, the resistant starch that I think makes the most sense to me is probably lentils. Lentils contain quite a bit of resistant starch as well. This is your area and your expertise, but it can’t hurt by increasing and ingesting those if you don’t have other issues. And again, the other note or the caveat to that, which you’re aware of, Chris, is that you can also cook the prebiotics right out of the onions, too.

Chris Kresser: Sure.

Jeff Leach: You can caramelize them and reduce them down to mono- and disaccharide and then game over. A little bit of cooking is not a bad thing, but I think it’s time for the apple to move over. I think an onion a day may keep the doctor away.

Chris Kresser: Right!

Jeff Leach: My apologies to the apple industry.

Chris Kresser: Yeah, exactly! One other note for people who are listening to this: One of the things that got me thinking about this in the first place was that I had a lot of patients coming to me who had been on the GAPS diet. I don’t know if you’re familiar with that, Jeff.

Jeff Leach: Yeah, I’m very familiar with it.

Chris Kresser: Yeah, and they had done the GAPS intro, which for those of you who aren’t familiar with it, it’s essentially just meat and broth for a period of time, and it can be tremendously effective and therapeutic for people who are dealing with gut pathogens and small intestinal bacterial overgrowth, and one of the reasons is that it literally starves the bacteria because they have nothing to eat or very little to eat. But what I started to see is that people who stayed on that kind of protocol for a long period of time, they would improve and feel better, and then after a while they’d start to feel worse and worse and worse. And I began to suspect that part of the reason that they were feeling worse is that the thing that they did, which was therapeutic initially, i.e. starving their gut bacteria because they had a lot of bad bacteria, then actually became harmful over time because they weren’t only starving their bad bacteria, they were also starving their good bacteria. That’s when I started to advocate for GAPS being looked at as a more temporary therapeutic approach, and in fairness, even the creator of it, Natasha, has talked about it that way for the most part. But I saw a lot of issues with people who were staying with that really extreme early intro approach and started to recommend that people add some more starchy tubers and other starchy types of plants and resistant starch into their diet as they improved in function so that they could preserve their good gut bacteria without completely decimating it.

Jeff Leach: Yeah, that’s a great observation. Again, if you think about it from an ecosystem perspective or from an ecosystem restoration perspective, if you take any ecosystem like the gut, the microbiome, and if you starve it, you’re spot on. If you starve your backyard and all the diversity of plants, if you just starve it of nutrients, all ships go down with lowering water. And that perturbation, if you will, it wouldn’t be on the same level as an antibiotic, but it is a perturbation; it is an insult. And when you insult an ecosystem, insults like fire, drought, nutrient overload or nutrient deprivation, any of these perturbations typically result in a flourishing of weedy species, in this case, opportunistic pathogens. I know the GAPS diet. I don’t know the lady who wrote it, and so it’s kind of out of my pay grade to talk about it too much, but from an ecosystem restoration standpoint, it makes absolutely no sense whatsoever to starve your gut microbiome at any level. That’s like people who do colon cleanses. I just want to cringe. Unless you have some very specific medical reason to do it, you might as well just let somebody hit you in the mouth. It makes no sense at all.

Chris Kresser: Wash out all your beneficial gut flora as quickly as possible.

Jeff Leach: Yeah! And again, anybody who’s ever tried to maintain a yard and had a drought or you light the backyard on fire, weedy species and opportunistic things come back, and that’s exactly what’s going to happen. You’d probably be better off nurturing it a little bit rather than trying to starve it as an idea. But you know, as you said, who knows? It seems to have some early benefits, but long term it clearly doesn’t make any sense, and I would argue that it probably doesn’t make any sense initially either. But who knows?

How People Can Get Involved in the American Gut Project

Chris Kresser: People definitely have benefit from it up front, but there are a lot of things that provide benefit but also can cause harm, so we can’t necessarily use that as a measurement.

OK, Jeff, so we’re coming up on the end here, and you mentioned earlier that you really are looking for people who are doing paleo and specifically low carb paleo diets. There are a lot of folks who listen to this show who probably fall into one or both of those categories, so how can they get involved?

Jeff Leach: The paleo group and the low carb group are very interesting to the research team. To put this in perspective, there are probably about 50 different people working on the American Gut Project right now. They’re all volunteers. We have over 80 or 90 total collaborators. But there’s a big interest, and it’s an interesting dietary group because they do keep good records and they pay attention to what they eat, so if we could increase the paleo participants and the low carb participants in the group, that would be fantastic. And people can just easily sign up. You can go to HumanFoodProject.com. Just follow the links. It takes a $99 donation to get in the game, and again, this is not a for-profit business. It’s completely volunteers. All of that money goes to lab supplies and mailing. I think there are one or two actual paid positions, but not at the research level.

Chris Kresser: Nobody’s getting rich.

Jeff Leach: Not even close! And I think the people who are getting rich are the fundraising sites or the crowdsourcing sites. They get a piece of the pie.

Chris Kresser: Right.

Jeff Leach: So, you can go and sign up, but a way to reduce the cost is if you can get one or two other people. It’s a donation of $99, but if you do two samples, it’s $180. In other words, you can get it down to about 80 bucks a sample if you get a couple of friends. And then you could have all the kits shipped to one address, and then you could distribute them to your friends. A bug buddy, if you will.

Chris Kresser: Mm-hmm.

Jeff Leach: That’s a lot of fun. We started in November. We just started releasing results. We’re kind of catching our stride right now, and we’re turning the samples around much quicker, so if you get a sample in, you could expect results within a few short months opposed to maybe six months. Now we’re starting to accelerate, and so anybody that participates will do us a lot of good and really help us reach that 20,000 number. Everybody’s going to benefit from this. Also I can’t stress enough that if you participate in the project, it’s a huge teaching moment, and I’ve watched people go through this kind of metamorphosis of signing up. Then they start listening to people like you, Chris. You pay a lot of attention to the microbiome, and you’re spot on 99.999% of the time, which is as good as anybody’s ever going to be, and you talk about it in a way that people understand. And once people get involved in American Gut, they start researching different bacteria, they start paying attention to a few more press clippings, and then when they get their results, I can tell you – I mean, I’ve been collecting my poo for a long time and keeping it in the freezer and having my own stool samples analyzed, which is a little creepy, but maybe that’s why I’m not married anymore!

Chris Kresser: All in the name of science, Jeff.

Jeff Leach: All in the name of science. But it’s unbelievably empowering when you actually see this data. It’s very different than your cholesterol level or any other kind of diagnostic. When you see that data, it literally takes your breath away because you see what your diet and lifestyle is and how it may shift those around, and it’s literally within your control… for most of us, not all of us. Save money on your next pair of Nike shoes, save money on the next gym membership, and get your microbiome sequence. It may be the best thing you do for your health in the next year.

Chris Kresser: You are what you poop, and your poop doesn’t lie.

Jeff Leach: Hey, I’m going to borrow that!

Chris Kresser: I got a new slogan for you! No charge.

Jeff Leach: And also if people want to follow along with what we’re doing in Africa, I’m headed back out in December and January. I’m actually going to become a Hadza hunter-gatherer for two months and try to shift my gut microbiome to look like theirs. We’ll be blogging and podcasting, if you will, from the field while we’re out there, so people can follow along and participate as well.

Chris Kresser: That’s really cool. Is that the HumanFoodProject.com as well?

Jeff Leach: Yeah, that’s HumanFoodProject.com. And anybody who signs up for the American Gut Project, you’ll be able to, within the next few months, compare your bacteria to Hadza hunter-gatherers who literally hunt the same animals and collect the same plants that our ancestors have done for millions of years minus the big megafauna.

Chris Kresser: Right.

Jeff Leach: They drink the same water. They’re literally walking on the ground of Homo erectus. You could throw a rock and hit Olduvai Gorge from the study area.

Chris Kresser: Wow.

Jeff Leach: So, you’ll be able to compare your gut bacteria to a population of people that don’t have any agriculture, that don’t take antibiotics, they’re all vaginally born, they all breastfeed for 2-1/2 years, they’re covered in nature’s blanket, they’re connected to the gut microbiota of all the animals on the landscape through the hunting and the gathering, all the bugs associated with the berries and the tubers. So, you really see how you compare to an ancestral population that I’m going to go out on a limb here and say it’s probably as close to a normal or optimal microbiome that we’re ever going to see in any ancestral population on Earth.

Chris Kresser: Right. Well, that’s amazing, Jeff, and we’ll have to have you back when you get back from that trip. I’m sure you’ll have a lot of new insights and interesting things to share with us. We originally tried to hook up while you were in Africa, and that didn’t work out for probably obvious reasons. I imagine that when you’re living as a Hadza hunter-gatherer, you probably don’t have a high-speed broadband internet connection.

Jeff Leach: Actually I’ll be the only Hadza hunter-gatherer with a satellite dish for a Wi-Fi uplink, so I am the outcast, and I’m the light-colored guy. You can’t miss me.

Chris Kresser: Yeah, exactly. Well, thanks for doing this work, Jeff. It’s so important. I really believe that if the 20th century was the age of antibiotics and killing bacteria, this 21st century is going to be the age of probiotics, and by that I don’t mean probiotic supplements. I mean pro life of the microbiota and the study of it and how it affects our health. There are things like fecal transplants and what we’re learning from that and the possibility of evolving that treatment to something that can really save lives, first of all, with things like C. diff, but not only that, affect a lot of other conditions that aren’t necessarily even related to the gut. It’s just, I think, as a clinician, one of the most exciting and promising therapeutic areas of study right now.

Jeff Leach: I think you’re exactly right. And one other thing – I mentioned it earlier – one of the things that we’re doing is we’re transplanting these Hadza hunter-gatherer fecal samples and we’re humanizing mice in Justin Sonnenburg’s lab. We’re also doing it in Maria’s lab in New York. We’re also doing it in the chemostat model that Emma developed in Canada to see if it’ll clear C. diff. So, some Hadza poo will end up in some germ-free mice in the United States, which will be interesting. And as a side note, I’m really looking forward to your book coming out. I’ve followed it and your progress over the last year, and so I’m excited about seeing a copy of it. I think it’s going to be a significant contribution to the paleo diet plus, if you will.

Chris Kresser: Thanks, Jeff. I appreciate that. OK, everybody, HumanFoodProject.com. Head over there and make your contribution to science and also do something for yourself. I think, like Jeff said, it’s incredibly empowering when you see what’s coming out of you that tells you more than anything else, perhaps, about what’s going into you and the state of your overall health. So, do yourself a favor and do this evolving body of science a favor and go sign up, especially if you’re on a low carb version of the paleo diet or a low carb diet at all. And, Jeff, I want to thank you again for coming on the show. It’s been a pleasure.

Jeff Leach: Thanks, Steve and Chris. Anytime!

Chris Kresser: Take care.