Exercise and/or Genistein Do Not Revert 24-Week High-Fat, High-Sugar Diet-Induced Gut Microbiota Diversity Changes in Male C57BL/6J Adult Mice

The gut microbiota (GM) has been hypothesized to be a potential mediator in the health benefits of exercise and diet. The current literature is focused on the prevention effects of exercise and diet and could benefit from exploring whether these treatments alone or combined can treat obesity via the gut microbiome. This study aimed to explore the effects of genistein, exercise, and their synergistic effect to revert diet-induced obesity and gut microbiota changes. A total of 57 male adult C57BL/6 mice were randomized to 24 weeks of unpurified diet (chow) or a high-fat, high-sugar diet (HFD; 60% fat total energy). After the first 12 weeks, animals on the HFD were randomized into: HFD + chow, HFD, HFD + exercise (HFD + Exe), HFD + genistein (HFD + Gen), and HFD + Exe + Gen. We compared the body weight change between groups after 24 weeks. GM (α-diversity and ß-diversity) was profiled after sequencing the 16S rRNA gene by Illumina MiSeq. HFD + Exe + Gen significantly (p < 0.05) decreased weight gain relative to the HFD with only HFD + chow reverting the body weight change to that of chow. All diets including HFD reduced the GM richness (observed amplicon sequence variants) relative to chow with the HFD + Gen and HFD + Exe resulting in significantly lower phylogenetic diversity compared to the HFD. Data did not support an additive benefit to the GM for HFD + Gen + Exe. HFD + Exe + Gen showed a greater capacity to revert diet-induced obesity in adult male mice, but it was not as effective as switching from HFD to chow. Lifestyle treatment of HFD-induced obesity including exercise and genistein resulted in a reduction in weight gain and GM richness, but switching from HFD to chow had the greatest potential to revert these characteristics toward that of lean controls.