Researchers headed by a team at the Joslin Diabetes Center and Harvard Medical School have identified a type of bacteria in the gut microbiomes of marathon runners—but not sedentary people—that can boost the capacity for exercise. Tests showed that mice inoculated with a strain of the bacterium Veillonella atypica isolated from elite athletes were able to run for longer on a treadmill than control animals. The researchers found that the Veillonella bacteria preferentially metabolize lactate, which muscles produced during hard exercise, and convert it to the short chain fatty acid (SCFA) propionate, which the body can then utilize to improve exercise performance. The researchers suggest that Veillonella could be formulated as a dietary supplement to help increase the level of health-promoting exercise that might be undertaken by individuals who can’t normally exercise effectively.
“Having increased exercise capacity is a strong predictor of overall health and protection against cardiovascular disease, diabetes, and overall longevity,” said Aleksandar D. Kostic, PhD, assistant professor and corresponding author on the team’s published paper in Nature Medicine. “What we envision is a probiotic supplement that people can take that will increase their ability to do meaningful exercise and therefore protect them against chronic diseases including diabetes.” The team’s paper is titled, “Meta-omics analysis of elite athletes identifies a performance-enhancing microbe that functions via lactate metabolism.”
Previous studies have shown that that exercise is linked with changes to athletes’ microbiomes, but the effects of these changes aren’t known. To investigate whether specific gut bacteria might be linked with athletic performance and recovery, Jonathan Scheiman, PhD, who was a researcher in the lab of George Church, PhD, at Harvard Medical School, took daily stool samples from 15 athletes who ran in the 2015 Boston Marathon, and brought them to the Kostic lab for analysis to see which bacteria were present. Stool samples from the runners were collected and analyzed every day for a week before the marathon, and then again daily for a week after the marathon. The analytical results were compared with those from fecal samples taken from sedentary individuals.
The results showed that Veillonella species were far more abundant in the runners’ samples post-marathon than they were pre-marathon, and were also more prevalent among the runners than among non-runners. “One of the things that immediately caught our attention was this single organism, Veillonella, that was clearly enriched in abundance immediately after the marathon in the runners,” Kostic stated. “Veillonella is also at higher abundance in the marathon runners [in general] than it is in sedentary individuals.” An analysis of stool samples from an independent cohort of 87 ultramarathon runners and Olympic trial rowers both before and after exercise confirmed the increased abundance of Veillonella species post-exercise.
At this stage it wasn’t clear whether the findings had any relevance to the athletes’ performance, but when the investigators gave experimental mice a strain of V. atypica isolated directly from one of the runners, the treated animals were able to run for much longer than control mice. “Mice treated with V. atypica ran, on average, 13% longer than the control group,” the authors wrote.
It turns out that Veillonella species use lactic acid (lactate) as their primary food source, which they metabolize into the SCFAs acetate and propionate. Lactic acid is produced by and accumulates in muscles during prolonged strenuous exercise when oxygen is lacking, so it seemed feasible that Veillonella-related improvements in exercise performance might be related to the bacterium’s ability to remove excess lactic acid.
“As we dug into the details of Veillonella, what we found was that it is relatively unique in the human microbiome in that it uses lactate or lactic acid as its sole carbon source,” Kostic said. The suggestion that Veillonella may improve exercise performance by acting as a lactate sink was supported by studies showing that radiolabelled lactate injected into the tail veins of mice treated with V. atypica could cross the gut epithelial barrier into the gut lumen within minutes, and so would be accessible to the bacterium.
“Our immediate hypothesis was that it worked as a metabolic sink to remove lactate from the system, the idea being that lactate build-up in the muscles creates fatigue,” Kostic stated. “But talking to people like Sarah Lessard, [a clinical researcher at Joslin] and other people in the exercise physiology field, apparently this idea that lactate build-up causes fatigue is not accepted to be true. So, it caused us to rethink the mechanism of how this is happening.”
To try and find an alternative link between Veillonella and improved exercise performance the team carried out a metagenomics analyses in the elite athletes to identify which events were triggered by Veillonella’s lactic acid metabolism. They found that all the enzymes involved in metabolizing lactate to propionate were increased after exercise. “Across the entire ultramarathon and rower cohorts, there exists a group of gene families with differential relative abundance pre- and postexercise, representing every step of the enriched methylmalonyl-CoA pathway, degrading lactate into propionate …” the team wrote.
Interestingly, propionate has previously been shown to increase heart rate and maximum rate of oxygen consumption in mice, and to raise resting energy expenditure and lipid oxidation in fasted humans. The researchers considered that it might, then, be the production of propionate, rather than removal of lactate, that was the link between the bacterium and improved exercise. “Then the question was maybe it’s not removal of lactic acid, but the generation of propionate,” Kostic said.
To test this possibility the researchers investigated running capacity in mice given a propionate-containing enema. “Propionate was introduced intrarectally rather than orally because colonic absorption provides a more direct route for propionate to reach the systemic circulation, mirroring the location of Veillonella-sourced propionate,” they wrote. The experiments confirmed that compared with control mice, animals given propionate supplementation intrarectally were able to run on the treadmill for longer than control mice. The level of exercise improvement in the prionate-treated mice was similar to that of animals given oral V. atypica.
“These data illustrate a model in which systemic lactate produced during exercise crosses to the gut lumen and is metabolized by Veillonella into propionate in the colon, which in turn serves to promote performance,” the authors concluded. “Microbiome-derived SCFAs then augment performance directly and acutely, suggesting that lactate generated during sustained bouts of exercise could be accessible to the microbiome and converted to these SCFAs that improve athletic performance … We propose that the high-lactate environment of the athlete provides a selective advantage for colonization by lactate-metabolizing organisms such as Veillonella.”
The reported study is one of the first to directly demonstrate a strong example of symbiosis between microbes and their human host, Kostic suggested. “This is a really important example of how the microbiome has evolved ways to become this symbiotic presence in the human host … The microbiome is such a powerful metabolic engine. It’s very clear. It creates this positive feedback loop. The host is producing something that this particular microbe favors. Then in return, the microbe is creating something that benefits the host.”
Exercise is an important part of a healthy lifestyle, but people with metabolic disorders may not be able to exercise at a level that might have a tangible effect on preventing type 2 diabetes, for example. The new results suggest that giving people probiotic supplements containing Veillonella could provide them with enough of a boost for effective exercise. Direct dosing with a propionate pill wouldn’t work, as the short chain fatty acid would be broken down by digestive enzymes before it could take effect.
There are some questions that need to be answered through further research, the authors acknowledged. “Future studies are needed to help explain why there is an apparent preference for Veillonella and not any of the many other lactate-metabolizing organisms”