Effects of locust bean gum on cholesterol gallstones and the gut microbiota in lithogenic diet-fed C57BL/6J mice.

Locust bean gum (LBG) is widely used as a thickener, stabilizer, emulsifier, and gelling agent in the food industry. In this study, a lithogenic diet-induced mouse model of cholesterol gallstones was employed to examine the effects of dietary supplementation with 2% and 5% LBG. Compared to the 5% dose, the 2% dose demonstrated superior efficacy. Gut microbiota analysis revealed that the lithogenic diet disrupted the network formed by Bacillota and Bacteroidota. Intervention with 2% LBG increased the abundance of Bacillota and established a network dominated by this phylum, accompanied by the enrichment of functional genes related to two-component systems, quorum sensing and biofilm formation. In contrast, 5% LBG failed to restore the intestinal network and only elevated the abundance of certain specific members. Furthermore, 2% LBG significantly reduced the abundance of Desulfovibrio and the expression of genes involved in H2S synthesis, while also promoting a more pronounced increase in butyrate levels. Both 2% and 5% LBG suppressed HMGCR gene expression. Additionally, 2% LBG significantly downregulated the transcription of ABCG5/G8 genes and upregulated that of CYP7A1 and CYP8B1 genes, thereby decreasing cholesterol synthesis and secretion and enhancing its conversion into bile acids. Collectively, these results led to marked alterations in bile acid profiles across the groups, and consequently influenced the degree of gallstone formation. This study demonstrates for the first time that LBG dose-dependently protects mice against lithogenic diet-induced cholesterol gallstones and provides mechanistic insights into its protective effects.