Foxtail millet (Setaria italica) alleviates non-alcoholic fatty liver disease in high-fat diet/streptozotocin-induced diabetic mice through gut microbiota modulation

Non-alcoholic fatty liver disease (NAFLD), caused by increased hepatic fat accumulation, inflammation, and oxidative stress, is one of the most common complications of diabetes. The hypoglycemic effect of foxtail millet supplementation has been studied previously. However, the influence of foxtail millet on diabetes-induced NAFLD remains unknown. The present study investigated the role of heat-treated foxtail millet (HFM) in alleviating NAFLD-related phenotypic indicators and altering gut composition in diabetic mice. Our disease model was established using a high-fat diet combined with streptozotocin before HFM supplementation. In diseased mice, the consumption of HFM reduced hepatic total cholesterol by 21.13%, triglyceride by 18.59%, malondialdehyde by 42.64%, and increased superoxide dismutase by 14.98% in the liver, respectively. Also, fasting blood glucose and serum insulin levels significantly decreased by 30.11% and 30.09%, respectively. 16S rRNA gene sequencing analysis indicated that HFM alleviated NAFLD-related gut microbiota dysbiosis in mice. Specifically, HFM treatment regulated gut microbiota composition, enriched probiotics (Bifidobacterium, Prevotellaceae_UCG-001, and Allobaculum), reduced harmful bacteria (Peptococcus, Oscillibacter, and EscherichiaShigella), and elevated short-chain fatty acid concentrations. These findings demonstrated that the beneficial effects of HFM on NAFLD may be associated with changes in gut microbiota composition.