Propionate Secreted by Gut Bacteria Enhances Exercise Capacity

In recent years, ever more evidence has accumulated for the gut microbiome to be influential on health throughout life, and on the pace of aging. The size of the effect is an open question at this time, but it isn't unreasonable to think that it might be in the same ballpark as that of regular moderate exercise. The gut microbiome changes with age in characteristic ways, and this may produce chronic inflammation and other deleterious effects. Healthier older people tend to have lesser changes in their gut microbiome, a more youthful distribution of bacterial species. In animal studies, transplantation of gut microbe populations from young individuals to old individuals improves the health and life span of old individuals.

For all this, it is far from clear as to which mechanisms are important in the changes that take place in the gut microbiome. Is the age-related decline of the immune system allowing harmful bacteria to prosper? Is it related to dietary changes that tend to take place in later life? Are there other important cell populations in the gut that deteriorate, and this changes the maintenance of gut bacteria? While many questions remain to be answered, researchers are making useful inroads into discovering what exactly it is that beneficial gut bacteria are doing. For example, manufacture of propionate from dietary fiber is known to be helpful to health. Researchers have shown it to improve cardiovascular health, and some of the benefits of dietary fiber intake are most likely mediated by this activity on the part of gut bacteria.

In today's research results, scientists report on the discovery of a bacterial species prevalent in athletes that metabolizes lactate into propionate, and by doing so increases exercise capacity. This is a novel and most interesting finding, though of course we should always look carefully at the size of the effect before becoming too enthusiastic on the topic - glancing at the data in the paper, it looks like about a 10% increase in treadmill time for mice. The important mechanism is the presence of propionate, not the bacteria themselves. This adds evidence to past research that suggests that this compound should be developed as a dietary supplement.

Performance-Enhancing Bacteria Found in the Microbiomes of Elite Athletes

Researchers collected samples during a time span of one week before the Boston Marathon to one week after the Marathon. They also collected samples from sedentary individuals. They then analyzed them to determine the species of bacteria in both cohorts. "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. Veillonella is also at higher abundance in the marathon runners in general than it is in sedentary individuals."

They confirmed the link to improved exercise capacity in mouse models, where they saw a marked increase in running ability after supplementation with Veillonella. Next, they wanted to figure out how it worked. As they dug into the details of Veillonella, they found was that it is relatively unique in the human microbiome in that it uses lactate or lactic acid as its sole carbon source. Lactic acid is produced by the muscles during strenuous exercise. The Veillonella bacteria are able to use this exercise by-product as their main food source. "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. But talking to 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."

Researchers ran a metagenomic analysis, meaning they tracked the genetics of all the organisms in the microbiome community, to determine what events were triggered by Veillonella's metabolism of lactic acid. They noted that the enzymes associated with conversion of lactic acid into the short chain fatty acid propionate were at much higher abundance after exercise. "Then the question was maybe it's not removal of lactic acid, but the generation of propionate. We did some experiments to introduce propionate into mice via enema and test whether that was sufficient for this increased running ability phenotype. And it was."

Meta-omics analysis of elite athletes identifies a performance-enhancing microbe that functions via lactate metabolism

The human gut microbiome is linked to many states of human health and disease. The metabolic repertoire of the gut microbiome is vast, but the health implications of these bacterial pathways are poorly understood. In this study, we identify a link between members of the genus Veillonella and exercise performance. We observed an increase in Veillonella relative abundance in marathon runners postmarathon and isolated a strain of Veillonella atypica from stool samples. Inoculation of this strain into mice significantly increased exhaustive treadmill run time.

Veillonella utilize lactate as their sole carbon source, which prompted us to perform a shotgun metagenomic analysis in a cohort of elite athletes, finding that every gene in a major pathway metabolizing lactate to propionate is at higher relative abundance postexercise. Using labeled lactate in mice, we demonstrate that serum lactate crosses the epithelial barrier into the lumen of the gut. We also show that intrarectal instillation of propionate is sufficient to reproduce the increased treadmill run time performance observed with V. atypica gavage. Taken together, these studies reveal that V. atypica improves run time via its metabolic conversion of exercise-induced lactate into propionate, thereby identifying a natural, microbiome-encoded enzymatic process that enhances athletic performance.