Lactobacillus Taiwanensis Inhibits Gallstone Formation by Regulating Ileal Metabolism

In recent years, gut microbiota has been recognized to participate in gallstone formation via the gut-liver axis, yet the specific changes and roles of ileal microbiota remain unclear. This study aims to investigate the effects of microbial communities in different digestive tract segments on the formation of gallstones and the underlying mechanisms. Six-week-old C57BL/6J mice were randomly divided into a lithogenic diet group and a normal diet group. Ileal and colonic contents were collected separately for metagenomic sequencing.The Lactobacillus taiwanensis gavage model was constructed to compare its effects on gallstone formation and ileal metabolism. An intraperitoneal injection model of Lipoxin A4 (LXA4) was established to investigate the mechanisms by which Lactobacillus taiwanensis and LXA4 inhibit gallstone through Western blot analysis and ELISA methods. We found that there were significant differences in the intestinal microbiota between the group with gallstone formation and the control group in the small intestine and colon. Species-level analysis indicated that the lithogenic diet reduced the abundance of Lactobacillus taiwanensis in the small intestine. When Lactobacillus taiwanensis was administered intragastrically to mice, the incidence of gallstones decreased. Through metabolomics analysis and experimental verification, we demonstrated that Lactobacillus taiwanensis could down-regulate the expression of NETs in the liver and bile by increasing the level of LXA4, thereby reducing gallstone. The ileal and colonic microbiota exert site-specific effects in gallstone formation. Lactobacillus taiwanensis may inhibit gallstone formation by regulating ileal metabolism, may contribute to prevention and treatment of gallstones.