Mechanism Study on Lactobacillus acidophilus Inhibiting Cholesterol Gallstone Formation by Regulating FXR-TLR4/NF-κB Pathway and Intestinal Barrier Function

Abstract Objective: In this study, a mouse model of cholesterol gallstones was established, and interventions with Lactobacillus acidophilus were administered.The research verified that Lactobacillus acidophilus improves intestinal barrier function through the hepatic FXR-TLR4/NF-κB pathway, and explored its mechanism of action in inhibiting cholesterol gallstone formation. Methods :We procured 30 male C57BL/6J mice at 8 weeks of age. After seven days of adaptation on standard rodent diet, animals underwent randomization into three cohorts: controls fed regular chow and saline control group(ND group, n =10), the lithogenic diet and saline c ontrol group (HFD group, n =10) , and the lithogenic diet and Lactobacillus acidophilus intervention group(HFLA group, n =10).Mice in the ND and HFD groups were gavaged with saline, while those in the HFLA group received Lactobacillus acidophilus by gavage, one time per day across 8 consecutive weeks. Body weight was monitored weekly.After 8 weeks, mice were sacrificed.Serum was collected to measure levels of LPS, IL-6, and TNF-α. Gallbladder stone formation was scored, Gallbladder specimens underwent hematoxylin-eosin staining to assess histopathological changes. Hepatic samples were processed via Western blotting to quantify TLR4 and phosphorylated NF-κB P65 proteins. Intestinal tissues were collected to measure mRNA expression levels of FXR、ZO-1, Occludin, and Claudin. Results: L. acidophilus intervention attenuated body weight accumulation ( P < 0.05) and reduced stone formation indices relative to HFD controls; improved gallbladder inflammation in pathological findings;increased mRNA expression of MUC5AC ( P