Alcohol is one of the most common causes of liver disease in the developed countries. Alcoholic liver disease (ALD) has a broad spectrum of disorders, including steatosis, steatohepatitis, and cirrhosis. Several agents and approaches have been evaluated in patients with ALD, however, there is still no FDA (Food and Drug Administration) approved management for any stage of ALD. Moreover, plethora of evidence depicting importance of gut microbiota in the onset and development of a variety of diseases, has led to potential use of probiotics in ALD. 

The mechanism with which probiotics function is still poorly understood, despite several researches suggesting effectiveness of probiotics on the treatment of both experimental and human ALD. Various theories have been proposed till date consisting of modification of gut microbiota, improvement of the intestinal epithelial barrier function, regulation of the immune system and inflammation, and alteration of hepatic lipid homeostasis.

Among these, alterations of gut microbiota have been identified as one of the major mechanisms underlying probiotic function. Studies in experimental animal with ALD showed a dysbiosis in colon lumen contents, which was prevented by probiotic treatment. Similar findings have been corroborated by other studies revealed that supplementation with probiotics restored gut microbiota homeostasis and improved alcohol-induced liver injury. Along with qualitative and quantitative alterations in the microbiome, few studies showed that ethanol caused an increase in plasma endotoxin, fecal pH, hepatic inflammation, and injury. Moreover, it has been observed that Lactobacillus rhamnosus GG (LGG) supplementation can prevent the ethanol-induced pathogenic changes in the microbiome. Thus, restoration of gut microbiota and its regulation is critical in gut-liver axis, contributes to the beneficial effects of probiotics in ALD.

One of the important functions of gut bacteria is to metabolize food to produce metabolites that are beneficial to the host. The present study used a metabolomics approach and showed that heptadecanoic acid, a long chain fatty acid produced only by bacteria, was ameliorated by alcohol ingestion and increased by probiotic treatment.

Evidence based observations also suggest that gut barrier function and endotoxemia are key regulators of gut-liver axis in multiple disease conditions. Probiotic administration can reinforce the intestinal barrier and reduce endotoxin levels in both NAFLD and ALD. The epithelial cells form a lining with the paracellular space sealed by tight junctions (TJ) and adherens junctions, and is covered by a protective mucin layer that blocks most particles from direct contact with the epithelial cells. Alcohol consumption, directly affects the gut intestinal barrier at multiple levels including tight junctions, production of mucin, and recruitment and activation of inflammatory cells to the intestinal wall.

Gut bacteria metabolize ethanol to acetaldehyde by cytochrome P450 2E1 (CYP2E1) that leads to development of large number of reactive oxygen species (ROS), which results in damage of intestinal barrier components including mucus layer and tight junctions. Probiotics by modulating certain gut bacteria contribute to intestinal barrier function, which further reduce metabolism of alcohol and ROS production in the intestine. Additionally, intestinal inflammatory cells such as mast cells also impact alcohol-induced epithelial barrier dysfunction. Alcohol-induced barrier dysfunction is correlated to local and systemic production of proinflammatory cytokines such as TNF-α and IL-1β. Various researchers have highlighted that beneficial role of probiotic administration in reducing alcohol-induced systemic and intestinal TNF-α and IL-1β levels, thereby establishing the therapeutic potential of probiotics on gut barrier integrity in ALD. Besides, probiotics are known to exert their favorable effects through modulation of hepatic AMPK activation and Bax/Bcl-2-mediated apoptosis in the liver.

Therefore, it can be summarized that ALD is closely related to gut microbial alterations and gut bacteria and its products play a crucial role in its progression, thereby establishing probiotics as a therapeutic tool for the prevention and/or treatment of ALD. There is rising trend in the utilization of increasing numbers of probiotic strains and related products in the successful treatment of ALD, however, the accurate mechanisms underlying the role of probiotics in regulating gut microbiota, intestinal barrier function, and ALD require further researches. 

Source: Li F, Duan K, Wang C, McClain C, Feng W. Probiotics and Alcoholic Liver Disease: Treatment and Potential Mechanisms. Gastroenterol Res Pract. 2016;2016:5491465.