Multi-omics analysis of the gut-liver axis revealed the effects of different exercise interventions in NAFLD mice

BACKGROUND: Growing evidence indicates that gut microbiota may play a potential role in NAFLD. Exercise was recognized as an effective intervention for NAFLD, but the effects of these exercise modalities on gut microbiota in NAFLD remain unclear. RESULTS: C57BL/6J mice were divided into a normal diet control group (NC) and a high-fat diet (HFD) group. After 8 weeks on the HFD, the mice were further divided into three groups: HFD, HFD + AE (HAE), and HFD + RE (HRE), and treated for 12 weeks. Body weight and liver weight of the mice were measured, and samples (blood, liver, colon, and feces) were collected for serum and liver biochemical analysis. RT-PCR was performed to analyze genes related to intestinal barrier function, along with 16 S rRNA gene sequencing and RNA-seq analysis. AE and RE effectively mitigated HFD-induced increases in body weight and liver weight in mice. Serum and liver lipid levels, as well as liver enzyme levels, were significantly reduced following AE and RE interventions. Additionally, HFD-induced gut microbiota dysbiosis was reversed by AE and RE interventions. These interventions increased the abundance of the beneficial bacterium Odoribacter while eliminating the harmful bacteria Mycoplasma and Lachnoclostridiumgan. Specifically, AE increased the abundance of beneficial Candidatus_Sacleftimonas and reduced harmful Enterococcus and Dubosiella, while RE enhanced beneficial Christensenellaceae_R-7_group and reduced harmful Streptococcus and Lactococcus, thus modifying intestinal metabolism. Transcriptomic analysis revealed that liver improvement through AE and RE was associated with lipid metabolism and inflammatory genes, which exhibited consistent changes with the gut microbiota. CONCLUSION: AE and RE could effectively prevent HFD-induced NAFLD and might serve as a reference for understanding the contribution of the gut microbiota due to their effects on altering liver lipid metabolism and maintaining gut microbiota homeostasis. Meanwhile, we suggest that combining AE and RE may result in more significant improvements.