Effects of Broad-Spectrum Antibiotic Treatment or Germ-Free Status on Endurance Performance and Exercise Adaptations in Mice.

PURPOSE: Endurance exercise alters the gut microbiome independently of diet. The extent to which gut microbes are responsible for physiologic adaptations to exercise training is unknown. The purpose of these experiments was to determine the role of gut microbes in performance and muscle adaptation to 6 wk of voluntary wheel running (VWR) in mice. METHODS: We depleted microbes with broad-spectrum antibiotic (ABX) treatment and used germ-free (GF) mice to determine effects on adaptations to VWR. Male and female C57Bl/6 mice ( n = 56) were assigned to daily VWR or sedentary conditions. After the intervention, treadmill endurance and glucose tolerance were assessed, and gastrocnemius and soleus tissues were harvested and analyzed for citrate synthase (CS) enzyme activity and expression of exercise training-sensitive genes. RESULTS: ABX treatment and GF status resulted in VWR volumes ~22% and 26% lower than controls, respectively. Analysis of variance revealed that, although VWR increased treadmill endurance, ABX had no effect. GF status significantly reduced treadmill performance in trained GF mice after training. VWR increased gastrocnemius CS enzyme activity in all groups, and ABX and GF status did not reduce the VWR effect. VWR also increased muscle expression of PGC1a, but this was not affected by ABX treatment. CONCLUSIONS: ABX treatment and GF status reduced VWR behavior but did not affect VWR-induced adaptations in endurance capacity, CS activity, or expression of muscle metabolic genes. However, GF status reduced endurance capacity. These data indicated that reducing microbes in adulthood does not inhibit endurance training adaptations in C57Bl/6 mice, but that GF mice possess a reduced responsiveness to endurance exercise training, perhaps because of a developmental defect associated with lack of microbes from birth.