Exercise Prevents Weight Gain and Alters the Gut Microbiota in a Mouse Model of High Fat Diet-Induced Obesity

TLDR

Diet‑induced obesity is linked to alterations in gut microbiota, and while exercise prevents obesity, it is unclear whether it also modifies the microbiota during high‑fat diet exposure. The study aimed to determine how voluntary exercise affects the gastrointestinal microbiota of mice fed low‑fat versus high‑fat diets. Male C57BL/6 mice were individually housed, with exercise groups provided running wheels; fecal samples were collected at baseline, 6, and 12 weeks, and bacterial DNA was analyzed by qPCR for Bacteroidetes and Firmicutes and by Illumina MiSeq 16S sequencing, with data evaluated using ANOVA and Pearson correlations. Voluntary exercise prevented the high‑fat diet–induced weight gain, adiposity, and glucose intolerance, and it produced distinct shifts in gut microbiota composition, including an inverse correlation between exercise distance and the Bacteroidetes/Firmicutes ratio, suggesting microbiota changes may mediate exercise’s protective effect.

Abstract

Diet-induced obesity (DIO) is a significant health concern which has been linked to structural and functional changes in the gut microbiota. Exercise (Ex) is effective in preventing obesity, but whether Ex alters the gut microbiota during development with high fat (HF) feeding is unknown.Determine the effects of voluntary Ex on the gastrointestinal microbiota in LF-fed mice and in HF-DIO.Male C57BL/6 littermates (5 weeks) were distributed equally into 4 groups: low fat (LF) sedentary (Sed) LF/Sed, LF/Ex, HF/Sed and HF/Ex. Mice were individually housed and LF/Ex and HF/Ex cages were equipped with a wheel and odometer to record Ex. Fecal samples were collected at baseline, 6 weeks and 12 weeks and used for bacterial DNA isolation. DNA was subjected both to quantitative PCR using primers specific to the 16S rRNA encoding genes for Bacteroidetes and Firmicutes and to sequencing for lower taxonomic identification using the Illumina MiSeq platform. Data were analyzed using a one or two-way ANOVA or Pearson correlation.HF diet resulted in significantly greater body weight and adiposity as well as decreased glucose tolerance that were prevented by voluntary Ex (p<0.05). Visualization of Unifrac distance data with principal coordinates analysis indicated clustering by both diet and Ex at week 12. Sequencing demonstrated Ex-induced changes in the percentage of major bacterial phyla at 12 weeks. A correlation between total Ex distance and the ΔCt Bacteroidetes: ΔCt Firmicutes ratio from qPCR demonstrated a significant inverse correlation (r2 = 0.35, p = 0.043).Ex induces a unique shift in the gut microbiota that is different from dietary effects. Microbiota changes may play a role in Ex prevention of HF-DIO.