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 (VO 2max , 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 α-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. What is already known on this topic - Gut microbiota ecosystem directly affects exercise capacity and muscle energy metabolism. - Athletes with high exercise capacity exhibit greater gut microbiota diversity and an over-representation of some bacterial species compared to inactive individuals, but current available data present major bias including the lack of consideration of dietary habits and body composition. What this study adds - Exercise capacity is associated with atypical gut microbiota communities, independently of food habits and body composition. - Atypical gut microbial ecosystem from athletes with very high exercise capacity are related to high fecal propionate content, but negatively associated with gut microbiota α -diversity, bacterial density and gut microbiota functional abundance. - Depending on the donor’s exercise capacity, gut bacterial ecosystems affect insulin sensitivity, but not exercise capacity, of transfected mice. How this study might affect research, practice or policy: - These data open promising research perspectives: 1) to improve the management of the gut microbiota ecosystem of elite athletes and patients performing adapted physical activity for therapeutic purposes, and 2) to personalize FMT in patients treated for non-communicable diseases by including exercise capacity parameters in the clinical criteria for donor selection.