Lactobacillus plantarum may prevent cholesterol gallstone formation by restoring gallbladder motility through preserving Cajal-like cells in mice.

Abstract

Background: Gallstone disease is closely linked to gallbladder dysmotility and gut microbiota dysbiosis; however, the specific role of Lactobacillus depletion in this pathogenesis remains unclear. This study investigated whether lithogenic diet (LD) induced cholesterol gallstone formation is associated with Lactobacillus deficiency and evaluated the potential of Lactobacillus plantarum (L. plantarum) supplementation to mitigate stone formation by restoring gallbladder motility.

Methods and results: Here, we used a murine cholelithiasis model using C57BL/6 mice fed an HFD to characterize whether gallstone formation in relation to gut microbiota dysbiosis and gallbladder dysmotility. Lactobacillus depletion was identified as a hallmark of gallstone formation, which was concomitant with gallbladder dysmotility. To target this deficit, L. plantarum was administered via daily gavage in an intervention cohort. L. plantarum supplementation significantly inhibited stone formation and improved CCK-induced gallbladder emptying. Histologically, probiotic treatment preserved gallbladder wall architecture and recovered α-SMA and interstitial Cajal-like cells (CLCs) expression levels compared to controls. These findings suggest that Lactobacillus deficiency may contribute to LD-induced cholelithiasis by impairing gallbladder motility, and that L. plantarum supplementation effectively prevents stone formation by restoring the gut microbiota-gallbladder motility axis.

Conclusion: LD-induced gallstone formation is characterized by Lactobacillus depletion and gallbladder dysmotility driven by the loss of smooth muscle integrity and CLCs. Supplementation with L. plantarum effectively prevents gallstone formation likely by restoring impaired gallbladder contractility. These findings highlight Lactobacillus as a promising non-invasive therapeutic strategy to prevent gallstones.