Gut-derived endotoxin plays an important role in inititating and advancing alcoholic liver disease (ALD). Probiotics have shown the potential to treat the alcohol-induced liver injury that causes gut leakiness and endotoxemia in animal models and in human ALD. But the mechanisms of their beneficial action still remain unclear.

A study hypothesized that alcohol damages the adaptive response-induced hypoxia-inducible factor (HIF) and probiotic supplementation diminishes this impairment, repairing barrier function in a mouse model of ALD by increasing HIF-responsive proteins (eg, intestinal trefoil factor) and reversing established ALD. 

Lieber DeCarli diet containing 5% alcohol was fed to C57BJ/6N mice for 8 weeks accompanied with Lactobacillus rhamnosus GG (LGG) supplementation in the last 2 weeks. 

The following observations were made-

• A marked reduction in alcohol-induced endotoxemia and hepatic steatosis and improved liver function was observed after LGG supplementation. 
• Restoration of alcohol-induced reduction of HIF-2α and intestinal trefoil factor levels was observed after LGG supplementation.
• In vitrostudies using the Caco-2 cell culture model demonstrated prevention of alcohol-induced epithelial monolayer barrier dysfunction with the addition of LGG supernatant. 
• Gene silencing of HIF-1α/2α nullified the LGG effects, suggesting that the protective effect of LGG is HIF-dependent. 

Thus the mechanism of probiotic action for treating ALD has been explained by this study, along with suggesting the critical role of intestinal hypoxia and decreased trefoil factor in the development of ALD.

Source- Wang Y, Kirpich I, Liu Y, Ma Z, Barve S, McClain CJ, Feng W. Lactobacillus rhamnosus GG Treatment Potentiates Intestinal Hypoxia-Inducible Factor, Promotes Intestinal Integrity and Ameliorates Alcohol-Induced Liver Injury, The American Journal of Pathology, 2011;179 (6) :2866-2875. https://doi.org/10.1016/j.ajpath.2011.08.039.