A Tiny Training Partner In Your Gut?

IRA FLATOW: This is Science Friday. I’m Ira Flatow. Imagine this, the conclusion of the big race. Maybe it’s a major marathon or the Olympic 10,000 meters. The winner is asked what contributed to her success. And so she takes a moment to think and she thanks her family, her trainer, and her microbiome. Hm, sound a little bit far fetched? 

Well new research published this week in the journal Nature Medicine suggests that a kind of gut bacteria may help elite runners. Mice given the bacteria perform better on a treadmill test than mice without it. And mice given a chemical produced by the bacteria also performed better. 

So will we be seeing a probiotic shake added to the carb loading before the big race? Joining me to talk about it is Alek Kostic. He’s an assistant professor of microbiology and immunobiology at Harvard Med School and Diabetes Center in Boston. And one of the authors of that study. Welcome to the program. 

ALEK KOSTIC: Thanks so much for having me on. 

IRA FLATOW: You’re welcome. You studied the microbiome in some of these elite runners. how did you do that? 

ALEK KOSTIC: Well, it took a lot of work. And mostly the dedication of the first author in the study, Jonathan Scheiman who rented a Zipcar, and for two weeks straight went house to house picking up fecal samples from our cohort of marathon runners. 

IRA FLATOW: How did he pull that short of straw to do that? 

ALEK KOSTIC: I got to do all the analysis. He got to do all of the fun field work. 

IRA FLATOW: OK so the reason for that is that there were microbes, you believe, different in these elite runners than regular people. 

ALEK KOSTIC: Well yeah, at the outset we really didn’t know what to expect. I think from my perspective I do a lot of work in the microbiome in various diseases with a lot of focus on diabetes. 

And we were interested in, is there anything unique in the microbiome of supremely healthy people? And what better place to look than runners in the Boston Marathon. So that’s what prompted the question. 

I think at the outset, I don’t like to have hypotheses. I like to create data sets and kind of really analyze them, figure out what is unique that stands out? And let the data kind of guide me. 

IRA FLATOW: So you found that they had more of one kind of bacteria than normal folks, people are not marathon runners. 

ALEK KOSTIC: That’s correct. So what we found was a single genus of bacteria called Veillonella which isn’t so well studied. But it was not only at higher abundance in the runners after the marathon, but even before the marathon the runners had a higher basal level of that organism compared to sedentary controls. 

IRA FLATOW: And why would they have that? 

ALEK KOSTIC: The answer to that question we only kind of found out towards the end of the study. The reason why it was basally higher in the runners. But it has to do with a unique property of this organism, at least relative to most human gut bacteria. Veillonella uses lactate or lactic acid as its preferred carbon source and energy source. 

IRA FLATOW: So it likes to eat lactic acid. Isn’t that the stuff that muscles give off when you exercise? 

ALEK KOSTIC: Yeah, that’s exactly right. So this is a substance that you can think of as kind of a metabolic byproduct of exercise that the muscles are producing. 

IRA FLATOW: And so is the idea here that if they have an excess or they have more of this veillonella that they are eating the lactic acid. And so they can perform better without getting tired? 

ALEK KOSTIC: Right, exactly. And that was our hypothesis going into it. That is it possible that enough of the lactate is getting into the gut? And that this organism is serving as a lactate sink and removing the lactate from the system. 

Although the more we talked to experts in the field, exercise physiology, the more we became we came to understand this whole hypothesis that lactate causes burn and causes fatigue in the muscles is not so well accepted. So it seemed to us it had to be through some other mechanism. 

IRA FLATOW: So what do you think that is? 

ALEK KOSTIC: Well, what we’re able to show in our metagenomic analysis, and we looked at not just which bacteria were present in the gut microbiome of these runners. But every single gene that they carry, what we found was that that gene that metabolizes lactate was very highly abundant. 

But an entire pathway of genes downstream of that enzyme was also highly abundant. And this metabolic pathway converts lactate into a key short chain fatty acid, propionate. And so that got us thinking, maybe it’s not really the removal of lactate. But rather it’s what lactate is being converted into, proprionate. 

IRA FLATOW: All right, so could you investigate that? 

ALEK KOSTIC: Yeah, and so we had some ideas about why propionate could be important. So one, it’s known to be an important anti-inflammatory molecule. Also it’s a bio energetic substrate that epithelial cells in the intestine tend to prefer. 

In addition to that, there’s some literature out there showing that it increases cardiorespiratory fitness, increases cardiac output. And even has some direct central nervous system functions. And so because we saw this as a major end product produced by this bacteria, what we did was test whether that molecule on its own could be sufficient to reproduce the kind of beneficial effects that we saw in our mouse studies with the whole veillonella. 

IRA FLATOW: And could it? 

ALEK KOSTIC: And it could. And it could. And so the kind of difficult thing about these experiments is that you couldn’t just take propionate orally. So that’s not really a viable route because it gets metabolized rapidly by the liver. And so you need to introduce propionate right where it’s produced by the gut microbiome. 

And that is right in the colon. And so we had to do intrarectal installations of propionate in these mice prior to getting them on the treadmill. But similar to colonization with whole veillonella, we saw this increase of about 13% in the ability of the mice to run until exhaustion. 

IRA FLATOW: So you’re saying it’s not quite practical. You’re not going to be able to swallow this propionate because it’s not going to get where it’s supposed to. Yet getting it to where it’s supposed to may not be a pleasant experience for people. 

How shall I say? Is there a middle ground of how to get it to where you’d like to have it the way you want to have it? 

ALEK KOSTIC: Yes, definitely. And the answer is the microbes. Because they’re right there, at the right place, at the right time producing the substance. So at the right place because they live in the colon. And at the right time because when the colon starts getting this rapid influx of lactate produced by the muscles but that we show eventually crosses the epithelial barrier into the gut where it’s accessible by the bacteria. 

The veillonella is right there to convert that into propionate. So you have this perfect little enzymatic process that the bacteria are conducting to give you that shot of propionate when you need it. 

IRA FLATOW: So is there a way to eat ingest or whatever, get the bacteria you need in a health food store in a probiotic somehow? 

ALEK KOSTIC: No, so veillonella is currently not a probiotic. There is an effort right now to try to demonstrate safety for this organism and also do manufacturing on this organism. There’s a lot of troubleshooting to be done there. But it is a common member of the human gut microbiome. 

And something that is present in a lot of athletes, definitely most marathon runners that we saw. And then can you imagine then, why is it going back to the original question, why is it that veillonella is at higher abundance basally in marathon runners versus sedentary individuals? 

IRA FLATOW: OK, I’ll bite. Give me the answer. 

ALEK KOSTIC: Well, it’s because of this positive feedback loop. So what we think is happening, marathon runners are constantly training. Constantly producing lactate. This is creating a unique niche for this organism to thrive in the gut of athletes. And so the more that they exercise, the more their veillonella abundance goes up. 

And in return, veillonella is giving them a little bit of a boost in producing proposition propionate. So it’s forming this positive feedback loop in what seems to be an important symbiosis between the human and the microbiome. 

IRA FLATOW: So once they stop their exercising, if they stop marathoning, then the gut bacteria’s going away. 

ALEK KOSTIC: We haven’t shown that. But that’s what we would guess, yes. 

IRA FLATOW: And so you think that anybody could achieve this if they just get the right level of intensity in their exercise? 

ALEK KOSTIC: I think a lot of people can. The main question is, how do you get seeded with veillonella in the first place? 

IRA FLATOW: Ah-ha. 

ALEK KOSTIC: And definitely, some people have it, some people don’t. Even the athletes, some of the top athletes we looked at we’re absent for veillonella. So that’s why we think trying to create it into a probiotic is going to be something very useful. 

IRA FLATOW: Keep your eye on the drugstore or shelf for the probiotic. Are you working on that at all? 

ALEK KOSTIC: Creating it into a probiotic? 

IRA FLATOW: Yes. 

ALEK KOSTIC: Yes, this work has spun out into a company, FitBiomics. And the goal of FitBiomics is to do that safety testing and that manufacturing to produce this probiotic. 

IRA FLATOW: Well, I’m not surprised. Thank you very much, Dr. KOSTIC, for taking time to be with us today. 

ALEK KOSTIC: I appreciate it, thank you. 

IRA FLATOW: Alex Kostic, assistant professor of microbiology and immunobiology at Harvard Med School there in Boston.

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