Silk Fibroin Coated Lactobacillus Plantarum Lac16 Ameliorates Alcoholic Liver Disease by Modulating Bile Acid Metabolism and Gut-Liver Axis.

Alcoholic liver disease (ALD) is a major global health burden with limited therapeutic methods. Emerging evidence highlights the gut-liver axis as a critical role of ALD pathogenesis, involving gut microbiota dysbiosis, intestinal barrier dysfunction, and disrupted bile acid metabolism. Probiotics, particularly Lactobacillus plantarum, have shown promise in mitigating ALD, but their efficacy is limited by poor gastrointestinal survival. Here, we developed silk fibroin coated Lactobacillus plantarum Lac16 (SLac16) to enhance probiotic viability and evaluated its protective effects in a murine ALD model. SLac16 significantly attenuated alcohol induced liver injury, reducing serum ALT, AST, and lipid levels while suppressing hepatic inflammation. Mechanistically, SLac16 restored intestinal barrier integrity by upregulating tight junction genes of ZO-1 and occluding, while reshaping gut microbiota composition, including downregulation of F/B ratio and upregulation of Muribaculum. Notably, SLac16 modulated bile acid metabolism by increasing hepatoprotective secondary bile acids including chenodeoxycholic acid and lithocholic acid and activating the FXR/SHP/CYP8B1/MRP2/BSEP signaling axis, thereby reducing bile acid toxicity. Compared to uncoated Lac16, SLac16 exhibited superior gastrointestinal survival and therapeutic efficacy, demonstrating its potential as a novel ALD treatment. This findings highlight SLac16 as a multi targeted probiotic therapy that restores gut-liver homeostasis through microbiota modulation, barrier repair, and bile acid regulation.