Discussion
Overall, LGS exerts a remarkable protective effect on ALD mice through the gut microbiota mediated specific hexanoic acid production and GPR43/GLP-1 pathway.
Methods
In this study, an ALD murine model based on the National Institute on Alcohol Abuse and Alcoholism (NIAAA) method was established.
Results
The results showed that oral LGS treatment dose-dependently alleviated alcoholinduced liver injury and inflammation in mice through decreasing levels of ALT, AST and proinflammatory cytokines (TNF-α, IL-6, IL-1β). LGS significantly improved liver steatosis, enhanced activities of alcohol metabolizing enzymes (ALDH and ADH), and reduced the CYP2E1 activity. Notably, regarding most detected indices, the effect of LGS (particularly at medium and high dose) was comparable to the positive drug MTDX. Moreover, LGS had a favorable effect on maintaining intestinal barrier function through reducing epithelial injury and increasing expression of occludin. 16S rRNA sequencing results showed that LGS remarkably modulated gut microbiota structure in ALD mice via recovering alcohol-induced microbial changes and specifically mediating enrichment of several bacterial genera (Alloprevotella, Monoglobus, Erysipelatoclostridium Parasutterella, Harryflintia and unclassified_c_Clostridia). Further study revealed that LGS increased production of SCFAs of hexanoic acid in cecum, promoted alcohol-mediated reduction of GRP43 expression in ileum, and increased serum GLP-1 level.