Effects of γ-aminobutyric acid-rich fermented rice bran on hepatic histology, gut microbiota, and fecal metabolites in a rat model of high-fat diet-induced NAFLD-like hepatic injury.

γ-Aminobutyric acid (GABA)-rich fermented rice bran (GFRB) is a multi-component fermented food matrix with potential metabolic benefits, but its effects on high-fat diet (HFD)-induced liver injury and associated gut microbial and metabolic changes remain unclear. In this study, we characterized the metabolite profile of GFRB and evaluated its effects in rats with HFD-induced liver injury. Male Sprague-Dawley rats were fed a control diet or HFD with or without GABA or low- or high-dose GFRB supplementation for 12 weeks. Gut microbiota, fecal short-chain fatty acids, and fecal metabolomic profiles were further analyzed as exploratory outcomes. GFRB contained markedly increased GABA and was enriched in amino acid- and fermentation-related metabolites, including glutamine, ornithine, citrulline, lactate, and succinate. HFD feeding induced a relatively mild non-alcoholic fatty liver disease-like phenotype characterized by hepatic histopathological alterations, including fatty changes and inflammation. GFRB supplementation attenuated these hepatic alterations, as reflected by a reduced NAFLD activity score in the low-dose GFRB group and decreased hepatic interleukin-6 levels in the high-dose GFRB group. Exploratory analyses also identified alterations in gut microbiota composition and fecal metabolite profiles, particularly in amino acid- and nitrogen-related metabolic pathways. Overall, these findings suggest that GFRB may attenuate early HFD-induced liver injury, potentially through modulation of hepatic inflammation. The accompanying gut microbiota and metabolomic changes should be considered exploratory observations that warrant further mechanistic investigation.