Exercise Capacity Mediated by the Gut Microbiome.

Female C57BL/6J wild-type (WT) mice (5 months old) exhibited greater maximal exercise capacity for running distance (489 ± 15 meters; n=6, p<0.05) than age-matched male WT mice (307 ± 17 m; n=8), as well as a 21% greater capacity for work to exhaustion. We hypothesized that these observed differences may be mediated by gut microbiota, as the sexes are known to have distinctly different microbiota. Predominant species in the male mice were found to be Faecalibacterium prausnitzii, Roseburia intestinalis and Allobaculum spp. while female mice had predominantly Parabacteroides goldstenii and Eubacterium coprostanoligenes. To determine if microbiota contribute to exercise tolerance, we administered antibiotic therapy (ABX) in drinking water to eliminate gut microbes. ABX eliminated the enhanced exercise tolerance of WT females. We then examined a model of enhanced exercise capacity -- Regulator of G Protein Signaling 14 (RGS14) knockout (KO) mice -- which exhibit greater maximal running distance (648 ± 38 m vs. 405 ± 21 m; p<0.05) than age matched WT mice, as well as a 53% increase in work to exhaustion (n=10/group). There is no difference in the enhanced exercise capacity of RGS14 KO mice between males and females. The greater exercise capacity in the RGS14 KO mice was also abolished by ABX. In conclusion, the gut microbiome appears to be a key factor in mediating exercise performance, since eliminating its action with chronic antibiotic therapy also eliminates the enhanced exercise performance in female vs male WT mice and in RGS14 KO mice of either sex.