He Bai

Background/Objectives: Gallstone disease is a prevalent digestive disorder worldwide, with incidence increasingly linked to obesity, insulin resistance, and dyslipidemia. Emerging evidence suggests that intestinal microbial communities and their bioactive compounds play a central role in pathogenesis. Here, we aimed to clarify whether diet-related microbial alterations and circulating metabolites contribute to gallstone formation. Methods: We integrated dietary inflammatory index (DII) evaluation, genetic analyses of large-scale cohorts, and a cholesterol gallstone mouse model induced by a lithogenic diet (LD). Serum and fecal samples were subjected to metabolomic and metagenomic profiling, followed by multi-omics integration to identify links between microbial taxa, metabolites, and gallstone risk. Results: Higher DII scores were associated with increased gallstone risk. Genetic evidence supported bile acid and amino acid metabolism as potential mediating pathways, with Akkermansia muciniphila linked to decreased N-acetylarginine levels and CAG-448 showing an inverse association with glycodeoxycholate (GDCA). In LD-fed mice, shotgun metagenomics revealed enrichment of lithogenic taxa such as Bacteroides stercorirosoris and Enterocloster, whereas protective taxa, including Akkermansia muciniphila and CAG-448, were markedly depleted. Untargeted metabolomics confirmed elevations of GDCA and N-acetylarginine together with broader bile acid imbalance, amino acid stress, and long-chain acylcarnitine accumulation. Correlation analyses further showed that protective taxa were inversely associated with risk metabolites, whereas gallstone-enriched microbes displayed the opposite pattern. Conclusions: This study provides evidence consistent with a contributory role of gut microbiota–metabolite dysregulation in gallstone pathogenesis. Specific taxa (A. muciniphila, CAG-448) and metabolites (GDCA, N-acetylarginine) may serve as potential biomarkers or targets for microbiota- and diet-based prevention strategies.

Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease and is closely associated with metabolic diseases such as obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome. However, effective treatment strategies for NAFLD are still lacking. In recent years, progress has been made in understanding the pathogenesis of NAFLD, identifying multiple therapeutic targets and providing new directions for drug development. This review summarizes the recent advances in the treatment of NAFLD, focusing on the mechanisms of action of natural products, small-synthetic-molecule drugs, and combination therapy strategies. This review aims to provide new insights and strategies in treating NAFLD.