Lauren Petersen transcript

Written by Christopher Kelly

Sept. 29, 2016

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Christopher:    Hello and welcome to the Nourish Balance Thrive Podcast. My name is Christopher Kelly and today I'm joined by Dr. Lauren Petersen. Hi, Lauren.

Lauren:    Hi, Chris.

Christopher:    Thank you very much for joining me today. Lauren is a postdoctoral associate at the Jackson Laboratory for Genomic Medicine, which sounds very fancy. Lauren, can you tell us a little bit about yourself and your research.

Lauren:    Oh, for sure. So, like you said, I'm a post doc at Jackson Labs. I work for George Weinstock who has been a leader in everything genomics, so human genome project, human microbiome project. So, essentially, our lab is just focused on the human microbiome and I, in particular, have started my own project called the athlete microbiome project where I focus on looking at the microbiomes of cyclists to see what might be strikingly different in an athlete microbiome like in the gut versus a normal person.

Christopher:    And am I right in thinking that you are a mountain biker yourself?

Lauren:    I am, yeah. I actually started my own biking when I was 13 and I started racing when I was 14. And I've done everything pretty much almost every discipline. I've done cross. I started off as a cross-country racer. I went into downhill when I was 19, went pro with that, and now I'm a pro endure racer.

Christopher:    Wow, that's pretty cool. So, you must know, I'm sure -- This is a kind of a small world. I was introduced to Lauren by Jeremy Powers who was on my podcast a few weeks ago. The CEO of Nourish Balance Thrive is also a pro mountain biker. She's taking a bit of a break at the moment. Her name is Jamie Busch. But now she's married. Her name is Jamie Kendall-Weed now. You might even Jeff Kendall-Weed who formerly worked at Ibis and he's also a kind of trials and enduro rider as well.

Lauren:    Yeah, I've heard of them. I don't think I've ever met them. They're West Coast, right?

Christopher:    Yeah, exactly. They live in--

Lauren:    I lived in California a little bit but my other ventures to the West Coast had been rather limited. I mainly just stay on the East Coast.

Christopher:    Cool. Well, let's take a step back and talk about what the human gut microbiome is and why we should care?

Lauren:    Yeah. I mean, up until even like maybe ten years, I mean, I don't think anyone cared. We were brought up thinking bacteria are bad and you have always cleaning products, antibiotics to get rid of the microbes. With the advance in next generation sequencing technology, we started to really uncover that our guts are actually inhabited by like thousands of different species and microbes. You have all sorts of different bacteria. You have viruses. You have different protozoa, fungi, living down there. And they actually have been referred to as another organ or ours because they perform so many important functions.

    And your gut, inhabited by microbes everywhere -- your skin, your lungs, your teeth, obviously. Each part of your body has a very distinct microbial community. A gut, by far, has the largest number of organisms. Essentially, you're born sterile but even during birth you're exposed to microbes from your mom. The first couple years of life you get exposed to all different kinds of microbes. During that time, it's really important for you to have the right kind of microbes, have good diversity, because it actually plays a really important role in your immune system and even the development of your brain, and, of course, metabolism.

    So, all those microbes in your gut are performing amazing metabolic functions that your own body actually can't do. So, breaking down a lot of the different fibers and resistant starches and things like that. And they're providing all sorts of very important metabolites for us, certain vitamins, short chain fatty acids. Without your microbes, you'd be very, very unhealthy.

Christopher:    And talk to me about the human micobiome project. I'm kind of really interested to know some of the history of how we started testing the gut microbiome.

Lauren:    Yes, for sure. So, yeah, George, my boss, was definitely a leader on that. It started back around 2007. It was the National Institute of Health funded project. I mean, it was a huge collaboration where they essentially just sampled different areas of the human body just to get that first look at what's the healthy microbiota, the gut or around the nose. I mean, every body part possible, they kind of looked and they just wanted to define what a healthy microbiome was.

    So, that got wrapped up and now they're actually into the human microbiome project phase two. So, it's more longitudinal sampling and it's more looking at diseases. Our lab also looks at diabetes and the links between diabetes and the microbiome. And there's others that are looking at irritable bowel syndromes, even the vaginal microbiomes, looking at differences in women and how it might affect pregnancy and things like that.

Christopher:    And what have they found, generally? Can you summarize any of the findings of that project?

Lauren:    The first phase or to the second--

Christopher:    Well, both.

Lauren:    First phase, it was just kind of more of a first look, finding what's there, going to look what the gut microbiome should look like.

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    So that if you then go look at a diseased person, you'll know that the healthy gut is very diverse, that you have -- And everyone is going to be a little bit different. Diversity is key. And then, obviously, you find certain kinds of pathogens. So, your e-coli, your clostridium difficile, high levels that's indicative of some kind of dysbiosis or disease. And as far as the second phase of the project, they are actually still getting their first publications together. They're kind of still in the middle of all that. I mean, there's so many labs out there doing all sorts of different kinds of research. So, it comes down to a matter of having a really good diverse microbe community especially in your gut. That indicates good health.

Christopher:    Okay. Yeah, talk to me about diversity. So, the simplest analogy I can think of is one of pub in London that's really, really busy. You can imagine that if you're on the outside and you're a pathogen and you were trying to get into this pub, you can imagine that there's hundreds of people between you and the bar and the actual diversity would stop you from getting in. And maybe the same situation is going on in your gut. Is it that simple though?

Lauren:    Almost. Yeah. I mean, it certainly helps. Because you have certain community that you build up over time like during childhood, getting exposed to different kinds of foods and even going out and playing the dirt, and that kind of stuff. And we're actually still not sure how you pick up a lot of the microbes that you end up with and why certain kinds stick. You have certain kinds of microbes that actually can only live on like your mucosal layer. So, they live off the mucin that your own intestine produces and secretes.

    So, you have a very strong community like that. They can't really go anywhere else. And then you have everyone else living down there and they're all like, yeah, it's just kind of like warfare down there. They're all fighting for this niche. They'll do anything they can to stay. So, if you get exposed to a pathogen, like even like a salmonella, something like that, you'll get sick. Your body passes it right out. Anything else that you might come in contact that might be pathogenic, you might be sick for a few days and then between your immune system, and I'm sure your microbiome, your body just passes it on through.

    Whereas, if you don't have that really good microbiome and you get exposed to certain pathogens, that's when bad things can happen. And that's exactly what happened to me. I got Lyme disease when I was 11 and proceeded to kind of struggle with that for the next ten years, actually, where I just had repeated bouts where I felt really, really sick. I had positive test for Lyme disease, got all the antibiotics that you could name. I was on everything and they're all broad spectrum antibiotics. This was like 20 years ago. At that time you don't really think that, wow, this is really, really bad because you're wiping out your entire gut microbiome.

    And that had pretty devastating consequences for me just in terms of like overall health and the effects that it had on my racing. Really, really bad stuff. Because I ended up, even after the Lyme disease, I ended up with pretty bad chronic fatigue syndrome, really bad issues with my stomach. I mean, just the ability to digest food. And then when I went on to do my PhD I got exposed to certain kinds of microbial pathogens, because that was the focus of my dissertation, I just got even sicker because I came in contact with different kind of pseudomonas and serratia and things like that.

Christopher:    What, physical contact in the lab?

Lauren:    Yeah, because you're just handling it. Like even if wearing gloves, you're going to get exposed to things. All it takes is one microbe. And it happens more often than you think. But if you're healthy and you have, obviously, a good microbiome, you never are even aware that you come in contact with these things because they just come and go. You don't get sick. Whereas, I ended up getting pretty sick where, at most, I wasn't racing at all during my PhD but, I mean, I couldn't even if I wanted to.

    I think I may be road twice a week and it wasn't from lack of motivation. It was lack of good health. I mean, I was just so tired all the time. And it wasn't until I went to a conference actually, one of the Gordon conferences, they're kind of a smaller really good collaboration conference, where like Rob Knight, who is really, really big in the microbiome world, where he did the American gut project where you could send an actual stool sample, have it sequenced just by standard 16S sequencing, and you can get a profile back of what your gut look like.

    And when I went to the conference, I was like, I was just starting to hear about the microbiome and I was like really starting to wonder. I'm like, well, all these antibiotics I took for all these years, I wondered what the really did to me and I wondered what my microbiome looks like because I wondered if I had something wrong. I've been to the doctor. I can't tell you how many times during those years after the Lyme disease was completely gone and everyone told me I was pretty much crazy because all the blood test came back, any kind of stool testing they did, they're like, "You don't have anything wrong there."

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    Everything was fine. But I knew something was very wrong. It was just a matter of -- Basically, my own experiences in going to that conference and hearing about this American gut project work, this little green light went off in my head and I'm like, "Oh my god, that's probably it." So, sure enough, I sent in a sample and when I got the results back, I mean, that explained everything.

Christopher:    Do tell us. What did explain?

Lauren:    Oh my god. It was shocking, to tell you the truth. Your normal gut microbiome, you're dominated by two main phylum of bacteria and they're referred to as the firmicutes and the bacteroides. And normally, that's like about 90% of your community. And then you have a little other guys, little proteobacteria, other minor players. Well, I had pretty much no bacteroides, no firmicutes and I have all enterobacteriaceae, which are potential pathogens. So, essentially, if they get into your bloodstream they can kill you. That's pretty much all I had. Then I had just a lot of pseudomonas and serratia, things like -- It was just really bad. I actually pretty much cried for two weeks because I was blown away by just how bad it was.

Christopher:    You found this out from Rob Knight's American gut project, is that right?

Lauren:    Exactly. Yeah.

Christopher:    Wow. So, that's interesting. You managed to glean some useful clinical data from what was supposed to be an academic test.

Lauren:    Right. Exactly.

Christopher:    So, what the heck did you do? Like can you re-balance that?

Lauren:    About three years ago, I got these results back. I was in the last year of my PhD. So, I mean, the only, essentially, the only thing you could do was a fecal transplant. Because the only way that you can replace a bad microbiome with a good one is to first kill off the bad one with antibiotics and then replace it. I knew I had to go on antibiotics essentially because I had an infection. And I couldn’t leave all those microbes down in my gut.

    So, I started contacting doctors in the Northeast trying to find one who might be able to work with me. But at this point, unless you're part of the gut clinical trial or you have clostridium difficile, they won't even talk to you. So, I got pretty much shut down. I had a few actually did get back to me and said, "Well, your results are really interesting but we can't really do anything. Here's a list of clinical trials. So, if one pops up, you can contact them." But I knew that wasn't going to fly. I mean, I was so kind of almost creeped out by what was living inside of me. I was just like, well, I have to do something here.

    And my mom was actually the one who had done a lot of reading. She said, "We could just do it ourselves."I wasn't really comfortable with that at first. I'm like, "You do fecal transplant by yourself." So, normally, when you do a fecal transplant, you have a doctor, it's done through colonoscopy, you get a healthy donor, you get them screened. There's like all these steps you take to do it right. And I was kind of freaked out. I'm like I can't do it myself. It's such a bad idea.

    Because some people do do it themselves and you see some scary stories sometimes on blogs about how people have done it themselves and where they got their donor is some kind of frightening and no one is tested. Because there's not a lot of data yet on -- I mean, they work, right? So, people with clostridium difficile who are pretty much devastated by this microbe that's causing crazy diarrhea and they're in the hospital, they could do a fecal transplant and over 90% of them are cured. And it happens within a week, just because you've introduced back a healthy microbiome.

    I mean, all those other microbes will fight off and keep that clostridium difficile in check, actually. I was kind of freaked out but I was like, "Okay, we'll look into it." So, if you actually look through the literature, they started doing fecal transplants, some people, actually back in the '50s. So, it's not exactly like a new procedure. So, I did a whole lot of research. I found every paper I could on fecal transplants and turns out you could do it at home and you could just do it through like essentially an enema.

    The next step was to get antibiotics. I made an appointment with a gastroenterologist just in the area and went to him and just said okay. I showed him the results from the American gut project. He was just like, "Yeah, it looks like you could have some irritable bowel syndrome." He just didn't really quite get it.

Christopher:    And you said that's what I told you.

Lauren:    Yeah. Like, "No, no, I know I have something wrong." And he was just like, "Well." He wanted to argue with me about what kind of sequence they may have done. I don't know. I don't think he knew what to do with me, obviously. I just showed up in his office and I'm like, "I'm about to get my PhD, microbial genetics, and here's what's wrong with me and can you just give me some antibiotics?" And I think I freaked him out so much that he just gave me the prescriptions I wanted.

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Christopher:    It's like just get this woman out of my office.

Lauren:    He never wanted to see me again. He wanted nothing to do with me. He was just kind of like, "Oh my god." But with my background though and being a scientist, I knew what antibiotics would work because knowing what pathogens were there. And so, I made sure I also got the right ones from him. I proceeded to go on antibiotics and that just really -- But talk about being sick, like I could barely eat anything. Solid food was out of the question. All those mechanisms that your microbiome does for you in the gut, digesting your food for you, I had none of that going on.

    It was pretty brutal. And I was trying to write my dissertation at that time too and trying to find a job and all those crazy stuffs, just to find a postdoc. But I did find a healthy donor who had been tested. I mean, was extremely healthy, no alcohol, no drugs, really, really fast cross-country racer. I mean, couldn't be like more perfect if you wanted to donor to do this thing.

Christopher:    It's like using a surrogate parent. It's like he's going to carry my baby.

Lauren:    Yeah. When I was them, I was like, "Well, would it be okay?" And they're like, "Yeah, whatever you need." They're like, "I'll give you poop." So, very awesome.

Christopher:    And so they must have already been donating before to be screened like that. They must have done it before.

Lauren:    Well, not for this particular purpose. So, they had actually did get food poisoning when they had some like follow-ups with doctors and stuff just to get tested. Because when you do get food poisoning they run a gamut of tests. And just knowing, I mean, I've known the person all my life. I was like, "Well, if they didn't find anything except--" I think it was the salmonella. And they did follow up test and they didn't find anything else. That was good enough for me at that time because I didn't know what else to do.

    And I was also scared of really going to another doctor and saying, "Hey, I want to do a fecal transplant. Can you test this person for me?" I don't know how you would approach a doctor who might be willing to do that for you. But knowing that this person would, at this point I prefer not to say who they were, but knowing that they had been tested and that they were so healthy and, other than getting food poisoning once, had never any kind of intestinal issues whatsoever, and knowing what kind of diet they had, I was so comfortable just having them as a donor. And I'm like, this is fantastic. We had no problem.

Christopher:    And so what happened?

Lauren:    In 24 hours after finishing antibiotics, I did the whole thing, which is very, very unpleasant. It's quick. It's simple. And within a month, I started feeling a lot better. Even in the literature, they say if you're going to do this kind of procedure, it takes between two to four months for you to really feel the effects. So, within a month, I was starting to eat normally again. And then within two months, I got back on my bike and the effects there were instantaneous.

    So, when I was sick, like I said, I was maybe riding twice a week. And just one ride for like two hours would absolutely devastate me. I'd be so tired the next day. And then it would take me another day or two before I could even think about riding again. That's just how tired I was all the time. But all of that changed so dramatically. I mean, I got on my bike -- It's Northeast, so as soon as the snow melted and this was right at the two-month mark. And it was amazing.

    I mean, just getting on my bike the first time and being, you're not in good shape and it's cold out, and I could just feel such a huge difference in how I felt. And then the biggest thing was even after doing like two hours that day, the next day I got out and I'm like, let's just see how I feel. And I got on my bike and I could just do it right away again. I mean, just go out for another two hours and I was just like so blown away. I've been so busy with my dissertation and stuff and just kind of trying to feel better because it does take a while. But that was the first occasion like, wow, like my life is completely different. It's going to be so much better now.

    And it was. I mean, within the next month even after that, I mean, I had no more stomach issues. I had more energy than I knew what to do with just so I could work even harder in the lab, work longer hours. Like everything just changed. And all that frustration I felt for the last ten years just went away. It all came down to the fact that having the Lyme disease for so long and all those antibiotics just wiped out all those microbes, just left me tired and with stomach issues. And then just getting that new microbiome fixed everything. And then what I did is I had myself sequenced.

Christopher:    That was going to be my next question. So, what was the 16S data like afterwards?

Lauren:    We matched organism for organism. It was perfect.

Christopher:    I really see you had 16S data from the donor as well as you and it matched.

Lauren:    Absolutely, yeah.

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Christopher:    That's freaky. That's, obviously, completely different from your before data.

Lauren:    And then the first thing I did was like, okay, I want all the sequencing data. I got all the sequencing data and there's nothing left of the serratia, there was no -- like nothing left of any of the pathogens I had. They were all gone.

Christopher:    Oh my god, that's amazing.

Lauren:    I was even more blown away than I thought I would be by those results. I hoped it's mostly gone or at least kept in check now. And I couldn't even find them.

Christopher:    And how far do you think this reaches? So, obviously, there's some bacteria in the whole intestine. But especially with the testing as well, the 16S, you're only testing the lower bottom portion of the intestine. So, if you were to be able to sequence the bacteria there in the small intestine, do you know how well they would correlate?

Lauren:    That's a good question. I'm not sure. I know like your stomach and your small intestine tends to have other types of bacteria more of the lactobacillus and, I think, streptococcus and things like that. Yeah, that's a good question. That's harder to test on humans though.

Christopher:    Yeah. So, I just wonder what role those microbes play in your situation. It would appear that they didn't play much of a role at all.

Lauren:    Great, great. Yeah, it doesn't seem that way.

Christopher:    Wow, that's amazing. And how long do you think it's going to be before fecal transplant becomes something that gastroenterologists are thinking about?

Lauren:    It's already happening a little bit more now. But like I said, the FDA has no idea what to do though. I think that's the problem right now.

Christopher:    There's not a lot of money in this either, is there?

Lauren:    Exactly. So, that's why you see certain companies like Seres Therapeutics are all like trying to rush to be the first one to have a microbiome pill.

Christopher:    Right. I wonder whether one day you'll go on to a website and you'll be able to choose your microbiome. There'll be these phylogenetic trees and you have like the different features of each one, good for cross-country racers, not so good for enduro, definitely not for downhill, like choose your profile.

Lauren:    Yeah, absolutely. I'm sure that will happen one day. Actually, I'm positive it will happen one day. I'm sure it will be in pill form. Whether you swallow it or it goes up the other end that will be the question.

Christopher:    That's absolutely amazing. And so funny as well, when I got you onto this podcast, I had no idea that had happened to you and I thought we were just going to talk about the research you've been doing. That's actually an incredible story. I'm glad that I didn't script the outline to this podcast.

Lauren:    And this is why I study what I do, right? Because six months after I did the whole transplant, I did my first enduro race and I got like third or fourth. And then the next one, I won. And I've been winning consistently since then. And I've just been -- I mean, I feel like amazing on a bike and I'm in my 30s but I'm like now just figuring out like how to train and how to eat right for training and all this crazy stuff. And also eating right for my microbiome because I'm like, "Oh my god, I got to keep these guys going."

Christopher:    Right. So, how do you do that? What do you think is the best strategy for keeping the diversity?

Lauren:    Essentially, it's eating a lot of fruits and vegetables and eating as many different types of them as you can. Diversifying your diet is huge. Limiting your processed foods, limiting your sugars and things like that is huge. I don't eat any processed food at this point really, very little sugar.

Christopher:    You're not choking down those maltodextrin gels on the long climbs of enduro races?

Lauren:    Not usually. If anything, I might have one like Honey Stinger pack like in the middle of a race but I even try to avoid those at this point. But, yeah, usually just Honey Stinger, more the organic ones, rather than anything else. But even like protein bars they make, I won't go near those things. I just bring a bag of like walnuts and dried cherries for lunch. Because feeding your microbiome, I think, is more important than taking any probiotic, to tell you the truth.

Christopher:    Right. And tell me about -- have you continued to sequence your microbiome? Is it diversified anyway from the original donor or maybe you don't have that data?

Lauren:    I don't have it yet. I will actually have the data soon. I've actually included myself into the second phase of my project on athletes. It's where we're doing longitudinal sampling and I've actually included myself in the study just, yeah, to answer those questions. I mean, I qualified as a participant so I might as well do myself.

Christopher:    Yeah. That's amazing. Well, tell us about it, the athlete microbiome project.

Lauren:    Yeah. So, this is my little brain child. And, obviously, it came out of my own experiences. So, coming off of all those experiences and into a postdoc with George Weinstock -- And actually got my job because of my experiences. I saw him posted looking for postdocs in pharmacokinetics to work on the human microbiome and I'm like, and this was exactly pretty much the same week I did the fecal transplant. I saw those posts and I'm like, "Oh my god, this is amazing. If I can work on this as a living, this would be a dream come true." So, I contacted him and just wrote him a pretty colorful email just saying pretty much I knew exactly what a bad microbiome can do to you.

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Christopher:    Yeah. Isn't it amazing how easy those emails are to write when you just capture the right thing? It's just effortless.  And then you realize that it's really hard to write the application or the pitch or whatever you want to call it and then you realize it's probably not a good fit.

Lauren:    Yeah. And you always want to stand out but for the right reasons. So, it was just a matter of really good timing, in a way, it was almost meant to be because he wrote me right back and said, "Yeah, this is fantastic. Send me your letters of references and stuff like that." We set up an interview like almost immediately and it was fantastic. I mean, I got the job within a week of the interview, I showed up and pretty much from day one he was like, "What do you want to do?" And I'm like, "I want to look at athletes."

    At that time, I was just getting back into racing and I was like I really like to know had I gotten a donor who wasn't an athlete or who had maybe a different type of microbiome, would I have benefit as much in terms of trying to be an athlete myself again? So, getting that--

Christopher:    Oh my god, you just got so -- So many ideas are spinning in my head right now. Do you think that the fecal transplant is going to end up on the wider list of banned substances? All I need to do is just get Jeremy Powers to send me some of his poo and then I'll be competing with him next weekend.

Lauren:    Exactly. You're going to beat him at the next cyclocross race. But is that the future? It's not a matter of, I don't know, you can call it bacterial doping. You have a certain community of microbes. Maybe you're missing a few that are really good at breaking down pasta or certain kinds of fibers because that leads to better energy transfer. So, if you're missing microbes that -- like certain kinds of ruminococcus that breakdown starches, your pastas and your raisin, stuff like that, people that don't have ruminococcus don't break those foods down. And you can find them in their fecal matter afterwards.

    Whereas people who can break it down because they have ruminococcus, they benefit from those nutrients, the energy, the carbohydrates. There's a lot there, I think. We've started to uncover some of that a little bit just with the first phase of the project and, hopefully, we can really get some better answers with the second phase of my project.

Christopher:    So, tell us about the racers that took part in this study.

Lauren:    The first phase of the project was just essentially getting one sample from a whole lot of different kinds of racers. I kind of just networked and got people who were national level like racers for cyclocross, for cross-county, we did downhill racers and we did enduro races. So, kind of ran the gamut, just because I have no idea what I would find. No one had done this kind of research before. And even George was still kind of like, "All right, let's see what you find. Let's not spend too much time." And I'm like, "All right."

    And what we found was actually pretty striking. So not only we sequenced the DNA that was present -- Because you just take a stool sample, you take a really small portion and you just extract the DNA and you sequence it and that will tell you the profile what kind of microbes are there. But you can also sequence the RNAs, essentially the active genes within these microbes so you can get a glimpse into what microbes are most active within the gut.

    So, I had shared some of the data with you and what we found was pretty crazy. Whereas, in the general American population, essentially you have one of three kinds -- they call them enterotypes or basically your dominant driver in the gut. So, most people in America have a bacteroides-driven gut, which means that they're dominated by a genre bacteroides, obviously, and they're kind of like the jack of all trades of bacteria. They can just kind of like breakdown anything. And they tend to be more associated with like the Western diet even.

    So, with high animal fat and protein and kind of more your processed foods and things like that. Other people tend to have a different community that can be dominated by what's called prevotella. So, prevotella is actually a far West well understood microbe that you don't normally find it high levels within the gut microbes of Americans. You actually find it more in African tribes, actually. People tend to have guts that are dominated by prevotella. Certain areas in Asia. And it comes down to like their diet, so higher fiber. You don't see all that processed food and you tend to have higher prevotella.

    And what we find is that athletes, especially like cross-country or more of our endurance athletes, have gut microbiomes that are dominated by prevotella. And actually, my donor when I got myself tested was dominated by prevotella. And then it was crazy. It was like half of our cohort had this really, really high prevotella. And maybe like only a few people were dominated by bacteroides. And then the rest of our athletes kind of have what we call ruminococcus enterotype where it's essentially like a whole bunch of different firmicutes. I mentioned ruminococcus before. They breakdown all your starches and things like that. So, that was the rest of the athletes.

[0:30:00]

    So, it made perfect sense. It's just showing that there are some pretty crazy differences with the athlete mirobiome.

Christopher:    Right. So, of course, the $64,000 question is, I think you can guess it already, is the prevotella along for the ride or is the prevotella driving the difference between the athletes and the non-athletes?

Lauren:    Exactly. That's a very good question. And that is what we're getting at with the second phase of the project. Right now, I'm kind of the in the thick of it with, actually, still recruiting people, is that we're getting longitudinal sampling. So, we're not just getting one sample from an athlete but we're actually, and this is what's probably the hardest part, is we're getting them to take stool samples during race weekends.

    And it can be really hard. Obviously, it's not going to work for someone who travels a lot because you have to keep the samples on ice if you're traveling, refrigerator, freezer, things like that. The focus is not DNA but it's RNA. We're looking at what microbes are most active and what are they doing? What are the metabolic functions that are going on within your gut when you're rested, when you're getting stressed out both mentally and physically before a race, what happens the day of a race, what happens?

    And then my biggest interest is what happens after a race. So, what's going on in your gut during recovery? Are there certain microbes that are doing certain functions that help someone recover really fast? Because, I mean, we all know someone who recovers faster than yourself. Like I've always been -- That was my number one thing for years. Like why can everyone recover so much faster? And some people, and this can be between healthy people, where some people can go out for a really hard effort and the next day just go all over again and other people can't. That comes down to training, obviously, and eating well but even your own human physiology. But, I think, your gut microbes are also playing a role.

Christopher:    Yeah. I mean it has to be a huge perturbation when you go and do a really strenuous exercise because it's normal gut physiology, right? You see those adrenergic receptors activated, you restrict the blood flow and then what happens? Do you see, if you've got a gut full of the enterobacter that you talked about, does it then release a bunch of endotoxin into your bloodstream every time you exercise is a possibility, right?

Lauren:    Oh, absolutely. And just looking at anti-inflammatory microbes, are they doing something? Because everyone, if you do a really hard effort you just said you have, you can feel it in your gut. And there's lots of microbes down there that do have really strong anti-inflammatory effects. So, that's another thing that we're going to be looking at.

Christopher:    So, how many people are you looking for?

Lauren:    So, I actually just recruited my 25th cyclist, so we're keeping it on cyclists still. And what I've done this time is no downhill racers at all. It's more of a cardio effort. So, even enduro racing, I think is kind of like the lower limit, I guess, I would say, of people who are pushing themselves. And it depends on the enduro race. The ones out West are, obviously, a bit more taxing and they take several days whereas the ones on the East coast are shorter but definitely put in hard efforts.

    I guess, half of my cohort now are enduro racers and then the rest are cyclocross and some cross-country racers. So, we'll have kind of an even split of enduro and then cross-country. We're also recruiting a matching cohort of healthy controls. So, people who either don't exercise at all or just maybe do minimal amounts of exercise. Because you want to know like what's the normal variation in the gut, anyway, how much does diet influence the activity of certain microbes? It's important to have that control as well.

Christopher:    Cool.

Lauren:    It comes down to -- because there's like stuff in the literature about even the amount of calories that you consume can influence prevotella, is what we've seen or your certain lifestyles. You want a control for all of that.

Christopher:    Excellent. Yeah, talk about some of the individual racers that you sequenced. Who's the Ibis world cup racer? Are you allowed to tell me that? Is it secret?

Lauren:    I'm not supposed to tell you though.

Christopher:    Oh, man, maybe I could probably figure out from how much information you give me. You've basically given me his fingerprint.

Lauren:    I mean, that person probably wouldn't care if I mention him but I'm not at liberty to tell you. I mean, they could tell you if they wanted to but, no, I have to protect everyone's identity for sure. I mean, everyone even gets coded right off the bat. I'm the only person who knows who's in the second phase of the project, every paper work. I mean, even kits that we ship to people don't have their names on it. We try to control for all that.

Christopher:    Right. So, if people listening to the podcast were to get the data for themselves, is there a way for them to use the software that you've developed to identify which microbes are present? You can do the uBiome test, which is very inexpensive. I developed a small application in Python that pass the data from the uBiome test and I use that with a bio informatics library that was created by Rob Knight's lab to produce the phylogenetic tree.

[0:35:11]

    What I did was fairly trivial. But I could manipulate that data any way you see fit. So, is it going to be public, the algorithms and the software and the methods that you used to identify the--

Lauren:    Yeah. Absolutely, yeah. All gets published. It will be part of the paper. Yeah, if you know what you're doing, it's not hard.

Christopher:    So, maybe we should get people listening to this podcast. So, a lot of people listen to this podcast. Maybe we should get people to do the uBiome test. Do you know how different it is? It's definitely a 16S test, the uBiome test. How different is the sequencing that you're doing?

Lauren:    I have certain, I don't know, hesitations about 16S sequencing. You tend to miss certain kinds of microbes. Actually, your bifidobacterium and stuff like that won't get picked up by most universal like 16S.

Christopher:    Yes. So, we've been seeing that. Once you pass out the data and created a phylogenetic tree, it's obvious that almost nobody has bifidobacterium on this test, which is just--

Lauren:    Yeah. That's not true at all. It's there. And what we have found is -- So, we do metagenomic whole-genome sequencing for DNA and that is essentially like you just sequence all of the DNA there and then you kind of map that back to your databases. So, that's where you pick up all the bifidobacterium and stuff like that. Whether someone's on probiotic or not, it doesn't matter when it comes to things like that.

    And what I have found too is that 16S data, it can give you a really good overview. Obviously, it answered all my questions when I got my gut sequenced by the American gut project but it doesn't get really down to function at all. It can't tell you what strain you have. Or you have these genes or you're enriched for these kinds of functions. And when we do RNA seq, so that's for the RNA work, to see what's active, that's pretty much the same application as metagenomic whole- genome sequencing.

    So, you sequence all of the RNA there and then you map it back to these microbes again and see everything that's there. And what we have found is like if you can look at that prevotella cohort and you can kind of figure out, if you look at the database, you can get down to species level and it will tell you that it's prevotella copri, which is usually the dominant, so-called dominant species in these people.

    But what we have found is that when you try and actually take all the DNA from the metagenomic whole-genome sequencing is that our prevotella, in these athletes is nothing like the published sequences of the prevotella that exist right now. So, these people have completely different probably species of prevotella that don't even exist in the database yet. So, that's really exciting. That's why we're looking more into that right now. Because I don't think 16S can tell you that. Now, we're on to like all these potentially new species of bacteria that we're uncovering in these athletes. That's really cool.

Christopher:    It is really cool. I was going to ask you if there was a test available commercially then that could match what you're doing in the lab. I guess, the answer would be a fat no.

Lauren:    Yeah, pretty much. No.

Christopher:    So, do you think that -- where is this heading? Do you think it is going to end in a commercially available test?

Lauren:    Yeah. I would think so. And there has been even talk here at Jackson Labs about that, where is this going, and George wants to do something like that. What I'm doing right now is kind of like the perfect platform for that, right? It's coming down. And anyone who's in the know of the human gut, like they want their microbiome sequenced. They want to know what's there. Yeah, I think, right now, there's uBiome, which is good. Like I said, it's a good overview. If you want to know just what your gut community looks like.

    But, yeah, I think the future is going to be like a better probiotics, which is something I want to focus on, even like an athlete probiotic that actually works for you. Because a lot of the stuff on the market right now is pretty much crap. And we can see that even with just the samples that we got. Because people report being on these probiotics but you can't find any trace of them in their samples. They're either, A, dying before they hit the gut or they weren't alive to begin with in the pill. So, who knows? I think that's part of it.

    I think, I the future you'll probably be able to tweak your microbiome towards being a better athlete. I mean, it comes down to just helping people who go on antibiotics. Even a week of antibiotics, if you're on a broad spectrum, can have pretty crazy effects. And it takes your body up to a year to recover from that.

Christopher:    Right. Talk to me more about the antibiotics. Sorry, the probiotics. Did you actually test the capsules themselves or you just rely on what the athlete had told you that they were taking? How did it work?

Lauren:    We're doing both, actually. And we're actually working on that right now. We are actually testing out some probiotics in the lab right now and seeing if what these companies claim are in there, is actually in there. I don't have the answers yet but I should within a few months.

[0:40:08]

Christopher:    I'll definitely have to have you back on then once you've got some more data to tell us. You can't show any preliminary findings or anything like that?

Lauren:    I can. I was just going to tell you. What I can gleam off of what we have found so far and my own analysis delving into kind of the whole genome sequencing data that we have is that bifidobacterium, if you take a bifidobacterium based pill, we can't find anything. And bifidobacterium is so beneficial for your gut microbiome. It's amazing what it can do actually. It stimulates other microbes in your gut to produce things like butyrate which are like really anti-inflammatory and feed your gut cells. It's so beneficial.

    But I think that's a really hard one to work with. it's strictly anaerobic especially the ones that we work with in our lab because I tested all our -- Because we've been actually isolating organisms ourselves from a set number of athletes who know what we're doing and they're fine with isolating organisms. Because once you isolate an organism you can perform a whole-genome sequencing just on that organism and understand why it's different from anybody else's.

    

    So, we've got a whole collection of microbes now that we've been growing from these samples. Yeah, bifidobacterium is hard because it doesn't like oxygen. So, if you're going to manufacture something like a probiotic pill of bifidobacterium you're kind of shooting yourself in the foot right off the bat because it doesn't really like oxygen and I don't think it's going to like your stomach too much either. Whereas your lactobacillus, pills that are lactobacillus based, we find those in your gut, for sure, especially if you're actively taking them. Those have a much higher chances of actually making it down to your gut and doing their thing and they're highly anti-inflammatory and they have a lot of good effects, not as good as bifidobacterium. So, we find better correlations between like the lactobacillus-based probiotics and what you find in the gut.    

Christopher:    Okay.  And do you think there could be a solution for the bifidobcterium probiotic problem? Do you think somebody might be able to encapsulate it in such a way that it's alive?

Lauren:    I'm sure, yeah. And, I think that probiotics have been around forever and, I think, people were just kind of winging it and hoping that it would -- because it's a multi, like million if not billion dollar industry, these supplements. And I'm not saying that that's true for every species of bifidobacterium because I haven't looked at that but for what we have with that and from what I've done in the lab here, it's tricky. I think, yeah, getting to a point where you can have some kind of capsule that would prevent oxygen from getting in.

    The other thing is feeding it. So, your bifidobacterium, they love the fructan oligosaccharides. So, all your fibers. So, you have to feed it right too. I think coming up with a pill that not only like has the right kind of bifidobacterium but also maybe you can feed it at the same time would be the perfect solution.

Christopher:    That's amazing. Amazing. So, talk to me about some of the other findings from your athletes. I noticed that you find an association between alcohol use or vegetarianism or gluten-free diets as well. That was interesting.

Lauren:    Yeah, that was really surprising because I thought we would find more of that. And that might be because, again, we only had 33 athletes so, obviously, a bigger cohort you might find all those correlations. But no, I mean, it didn't matter if they ate meat, if they didn't. Everyone clustered more on what kind of racing they did rather than their kind of effect.

    So, the other thing too though is with that cohort is that we didn't get really strict like diet information because it was just a pilot study and we just wanted one sample. So, for phase two, we're going to get like really in depth their foods, I mean, item by item what they're eating, what they're drinking, how much they're exercising, how many calories they're burning. So, I think, we'll get a lot better answers over the next year with the second phase in the project.

Christopher:    And so, do you have an app or something that you're going to be logging all the stuff with?

Lauren:    I don't yet. I probably should.

Christopher:    Yeah. There's someone I can connect you with actually that's developing a very cool app that allows you to take pictures of your food and then he uses a Mechanical Turk to identify what you've eaten.

Lauren:    Oh, I misunderstood you. Okay, yeah. [0:44:25] [Indiscernible] MyFitnessPal for just the diet and things like that.

Christopher:    Yeah, I know. This is way better than that. I think this is going to be exciting. It's coming in this area. Yeah, for sure.

Lauren:    Awesome.

Christopher:    Cool. Well, this has been fantastic, Lauren. I'm really excited and thrilled to talk to you about all this stuff. Is there anything else that you'd like people to know about?

Lauren:    No. I mean, at this point, it's just my biggest recommendation is feed your microbiome right, lots of fruits and vegetables.

Christopher:    Yeah. The steak and butter ketogenic diet may not be optimal for reasons we don't fully understand yet.

Lauren:    Exactly. No. I've dabbled with that diet myself. I can say that, I think, a good balance is key.

[0:45:04]

    Good fat but also good carbohydrates. Like 20% protein, I think, is kind of the sweet spot. The rest is, yeah, 40% fats, 40% carbohydrates and having those carbs really clean, good healthy foods. Stay away from McDonald's.

Christopher:    I think that's given. For everyone listening to this podcast, they're already doing that.

Lauren:    Yeah. It comes down, I think, too, there's a lot of evidence for that. Your own host, your physiology can influence what kind of microbes do you have too. I think some of that will really come to light in the next few years as well, how the interaction between your own body and what kind of microbes you have. It would be really cool to see.

Christopher:    Excellent. This simply must be the first of a part of a series. I have to have you back on to find out what happens in phase two. I'm very excited about that. Well, thank you so much for your time, Lauren. I really appreciate it.

Lauren:    No, it's excellent. Thank you so much. That was very fun.

[0:46:06]    End of Audio

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