Distinct effects of highland barley and common buckwheat on gut microbiota and liver transcriptomics in high-fat diet-induced mice

Abstract Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver condition, influenced by factors such as obesity, insulin resistance, and hyperlipidemia. While ancient grains like highland barley (HB) and common buckwheat (BW) have shown potential to mitigate these factors, direct comparisons of their effects on NAFLD remain unclear. The present study investigated the impact of HB and BW on HFD-induced NAFLD and the underlying mechanisms, including the influence of gut microbiota and fecal metabolic profile. HB supplementation for 12 weeks significantly reduced fat accumulation, serum triglycerides, insulin resistance, and hepatic steatosis visualized through H&E staining. BW supplementation also reduced these parameters, though less pronouncedly. Besides, HB and BW altered the gut microbiota composition, enriched the abundance of probiotics, while reducing harmful bacteria. Specifically, HB increased the abundance of Ileibacterium and norank_f_Muribaculaceae, while reducing that of Mucispirillum and Helicobacter. BW elevated levels of Akkermansia and Lachnospiraceae_UCG-001, and lowered those of Mucispirillum and norank_f_Peptococcaceae. In addition, HB supplementation greatly increased fecal levels of succinic acid and L-aspartic acid, whereas BW supplementation raised levels of 2,3-dihydroxybenzoic acid, p-salicylic acid, pyrocatechol, and gentisic acid. Moreover, liver transcriptomic analysis revealed that HB upregulated LEPR, AMPKα1, and PGC-1α, while BW enhanced PI3K, AKT, and BCL-2 expression. Overall, HB and BW alleviated HFD-induced NAFLD through distinct modulation of gut microbiota, fecal metabolites, and hepatic transcriptomic profiles.