Oral antibiotics reduce voluntary exercise behavior in athletic mice

The gut microbiome can affect various aspects of both behavior and physiology, including exercise ability, but effects on voluntary exercise have rarely been studied. We studied females from a selection experiment in which 4 replicate High Runner (HR) lines of mice are bred for voluntary exercise and compared with 4 non-selected control (C) lines. HR and C mice differ in several traits that likely interact with the gut microbiome, including higher daily running distance, body temperatures when running, spontaneous physical activity when housed without wheels, and food consumption. After two weeks of wheel access to reach a stable plateau in daily running, mice were administered broad-spectrum antibiotics for 10 days. Antibiotic treatment caused a significant reduction in daily wheel-running distance in the HR mice (-21%) but not in the C mice. Antibiotics did not affect body mass or food consumption in either HR or C mice, and we did not observe sickness behavior. Wheel running by HR mice did not recover during the 12 days following cessation of antibiotics. The decreased wheel running in HR but not C mice, with no apparent negative side effects of antibiotics, suggests that the HR microbiome is an important component of their high-running phenotype.