Atypical gut microbial ecosystem from athletes with very high exercise capacity improves insulin sensitivity and muscle glycogen store in mice

Background. The gut bacterial ecosystem plays a key role in the host's energy metabolism, and potentially in the host's exercise capacity, recognized as a powerful predictor of health status and risk of mortality. Objective. To deepen our understanding of the gut bacterial ecosystem relationship with host's exercise capacity and energy metabolism, we characterized the gut microbiota in a cohort of healthy humans with heterogeneous exercise capacities, and next determined the impact of fecal microbiota transplantation (FMT) from donors of this cohort on energy metabolism and exercise capacity of recipient mice. Design. 50 male normo-weight participants (from inactive to elite endurance athletes) performed food frequency questionnaire (FFQ) and exercise tests to determine exercise capacity parameters (VO2max, fat oxidation, exercise energy expenditure). Metagenomic shotgun and metabolomic analyses were performed to characterize gut microbiota ecosystem and short-chain fatty acids (SCFAs) on human and mice fecal samples. Mice performed running exercise capacity tests and metabolic parameters were determined in skeletal muscle and plasma samples. Results. While our data support that the bacterial ecosystem appears to be modestly altered between individuals with low to high exercise capacities, we report that gut bacterial alpha-diversity, density, and functional richness are significantly reduced in athletes with very high exercise capacity. By using FMT, we report that the engraftment of these atypical gut microbiota improves insulin sensitivity and muscle glycogen stores into transfected mice. Conclusion. Our data highlight promising therapeutic perspectives in fecal transplantation from human donors selected based on exercise capacity parameters.