When you think of probiotics, immune function probably comes to mind first, with digestive function and overall metabolic health perhaps coming next. Athletic performance isn’t something typically associated with probiotics, but a study published last month in Nature Medicine has raised interesting questions about the role of gut flora in supporting exercise activity.
Researchers from the Joslin Diabetes Center in Boston compared fecal bacteria from a small cohort of Boston Marathon runners (n=15) to that from sedentary individuals (n=10). Stool samples were collected for up to 5 days before and after the marathon, and a distinct difference was noted in the abundance of the bacterial species Veillonella atypica. This organism has unique properties that may contribute positively to performance in endurance athletics, with potential to facilitate increased physical activity in populations that may benefit from it, such as those with obesity, type 2 diabetes or metabolic syndrome.
In the marathon runners, levels of Veillonella were substantially higher after the race than before it, but even before the event, levels were higher than in the sedentary cohort. Higher levels were also observed in ultra-marathoners and Olympic trial rowers post-exercise. The key feature of this bacteria is that it uses lactate as its sole fuel source and produces the short-chain fatty acid (SCFA) propionate as metabolic byproduct. Veillonella is not unique in consuming lactate, but most other bacteria studied to date don’t produce propionate specifically from lactate or produce much less of it than Veillonella. Levels of enzymes associated with conversion of lactic acid to propionate were much higher after exercise.
It was unknown what the role of Veillonella was in athletic performance—or even if it had a role—so the researchers designed rodent experiments to try to elucidate whether these bacteria were responsible for a beneficial effect on athletic performance or whether they were simply a byproduct of physical activity. And if there is a beneficial effect, is it due to the enhanced clearance of lactate, the increased propionate, or both? Muscles produce lactic acid during strenuous exercise. It was long believed that the buildup of lactic acid in working muscles is what leads to muscular fatigue, but this hypothesis is no longer accepted as true. So enhanced lactate clearance was unlikely to be the explanation.
To look more closely at the effect of propionate, researchers inoculated mice with propionate (via enema) to see if it would have an effect on running performance. The study explains that propionate was delivered rectally because “colonic absorption provides a more direct route for propionate to reach the systemic circulation, mirroring the location of Veillonella-sourced propionate.” Oral administration would not have tested the gut-associated effects of propionate, because as a SCFA, it would have been digested/metabolized before reaching the colon. The fact that Veillonella produces it inside the colon is instrumental to the observed effects. The propionate-treated mice had significantly increased maximal run times compared to untreated mice, leading researchers to conclude that the propionate was sufficient to account for the increased running ability phenotype.
In a separate experiment, mice were treated with either Veillonella atypica isolated from one of the marathon runners, or with Lactobacillus bulgaricus as a control. (L. bulgaricus was used as a control because it doesn’t metabolize lactate but would represent an increased bacterial load.) Mice treated with V. atypica ran an average of 13% longer than the control group. Additionally, post-exercise levels of inflammatory cytokines were significantly lower in the Veillonella-treated mice, which could have implications for exercise recovery.
These experiments helped to establish that lactic acid from the blood can be taken up into the intestines, where Veillonella uses it as a food source and generates propionate as a result. As to why this might be of specific benefit to athletes, the study authors “propose that the high-lactate environment of the athlete provides a selective advantage for colonization by lactate-metabolizing organisms such as Veillonella.”
“Gut colonization of Veillonella may be augmenting the Cori cycle by providing an alternative lactate-processing method whereby systemic lactate is converted into SCFAs that re-enter the circulation. SCFAs are absorbed in the sigmoid and rectal region of the colon and enter circulation via the pelvic plexus, bypassing the liver and draining via the vena cava to reach the systemic circulation directly. 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.”
Dr. Kostic provided a more “plain English” explanation: “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. This is a really important example of how the microbiome has evolved ways to become this symbiotic presence in the human host.”
In future research, Dr. Kostic and his team plan to further investigate the mechanisms of how propionate may affect exercise capacity, with the potential for this to translate into new therapeutic tools for metabolic health. People who could most benefit from exercise—such as those with low energy levels, obesity, insulin resistance or general metabolic dysregulation-- often have the least capacity to engage in strenuous activity, so if Veillonella is found to increase exercise capacity in the general population, it’s possible it could be helpful for these individuals. It may also have implications for boosting performance in athletes, military personnel and others who require a high level of physical readiness.
This research is very preliminary, however. Human sample sizes were small and the direction of causation is not known for certain. Dr. Emeran Mayer, a gastroenterologist at UCLA’s Geffen School of Medicine, noted that rather than Veillonella being responsible for enhanced exercise performance, it’s possible that some people develop higher levels of Veillonella in their guts early in life, and these people might be more likely to become athletes. Mayer also pointed out that it’s not yet known if Veillonella administered as a probiotic would increase levels of this bacteria in non-athletes, and if so, whether there would be undesirable side-effects that could outweigh the potential increase in physical activity.
In the interest of full disclosure, it should be noted that some of the study authors are founders and equity holders of FitBiomics, a company that seeks to identify new probiotic bacterial strains that may be beneficial in exercise performance and recovery.