Voluntary exercise alters energy balance and the gut microbiota in a time dependent manner in C57BL/6 mice fed a low fat diet.. Voluntary exercise alters energy balance and the gut microbiota in a time dependent manner in C57BL/6 mice fed a low fat diet.

Here, we investigated the effect of voluntary exercise on energy balance and related parameters, including the composition of the gut microbiota, in male C57BL/6 mice. Mice consumed a 10% energy (low) fat diet (LFD), with (RW+) or without (RW-) access to running wheels for eight weeks. The RW+ group had similar body weight trajectory and body composition to RW- animals, but consumed significantly more food by week three of the trial (p<0.05), as a result of higher intake during the dark phase. Metabolic activity was increased in the RW+, both in the light and dark phases, compared to RW- group and respiratory exchange ratio was significantly increased in the dark phase in the RW+ compared to RW- group, indicating increased tissue carbohydrate metabolism (p<0.05). This was supported by unchanged levels of plasma insulin and glucose and by a trend towards an increased expression of hypothalamic insulin receptor (INSR) (p=0.085), glucose transporter 1 (Glut1) (p=0.085), insulin receptor substrate 1 (IRS1) (p=0.065), fatty acid synthase (FASN) (p=0.071) and peroxisome proliferator activated receptor alpha (PPAR (p=0.052), all at the trial’s week 8 end point.High throughput DNA sequencing revealed subtle changes in the microbiota of the RW+ group relative to the RW- group. More specifically, at week 4 the RW+ cohort contained significantly higher proportions of Bacteroidaceae/Bacteroides and significantly lower levels of Clostridiaceae/Clostridium compared to the RW- cohort. When week 4 taxonomic data was coupled with PICRUSt-based predicted metabolic functional data, differences in the functional potential of the microbiota, with propionate metabolism and fatty acid biosynthesis were predicted to be significantly higher in the RW+ cohort at week 4, but not week 8. Thus, initial changes to the gut microbiota observed after four weeks of voluntary exercise preceded changes in host expression of genes involved in energy intake. This study suggests a time dependent, link between physical exercise, the gut microbiome and energy balance.