Lactobacillus rhamnosus GG Combined with Metformin Alleviates Alcohol-Induced Liver Inflammation in Mice by Maintaining the Intestinal Barrier and Regulating Treg/Th1 Cells.

Abstract

Disturbances of the intestinal barrier enabling bacterial translocation exacerbate alcoholic liver disease (ALD). Lactobacillus rhamnosus GG (LGG) has been shown to exert beneficial effects in gut dysbiosis and chronic liver disease. The current study assessed the combined effects of LGG and metformin, which play roles in anti-inflammatory and immunoregulatory processes, in alcohol-induced liver disease mice. A diet comprising 5% alcohol for 4 weeks was employed to develop an alcohol-induced liver injury model. Mice were orally administered LGG, metformin, or their combination on alternate days. Tight junction (TJ) proteins, gut microbiome composition, inflammatory cytokines, Jun N-terminal kinase (JNK), and p38 signals were assessed. When compared with treatment with LGG or metformin alone, combined LGG and metformin treatment substantially lowered the symptoms of inflammation, steatosis, and elevated liver enzymes caused by alcohol administration. Combination treatment significantly improved intestinal microecology, evidenced by the recovery of intestinal flora, TJ proteins, and intestinal villi. Combination treatment reduced hepatic inflammation by blocking p38 and JNK phosphorylation. The combination of LGG and metformin corrected immune-response dysregulation and improved ALD by enhancing the intestinal microbiome, restoring mucosal barrier integrity, modulating immune function, and decreasing liver injury. These results provide information for the development of intestinal microbiota-based preventive and therapeutic agents against ALD.