Understanding the complex gut microbiome and how it interacts with the host immune system has opened up pathways in the exploration for the treatment of liver disease. Alcohol-associated liver disease is a significant cause of death globally. Research has focused on the breakdown of the protective gut barriers, translocation of gut microbes to the liver and inflammatory immune response to microbes all playing a major role in the development and progression of alcohol-associated liver disease. This knowledge has helped in introducing alternative therapies to reduce alcohol-associated liver disease based on the interaction of the commensal gut microbiome and immune response. 

Therapeutic approaches targeting innate lymphoid cells (ILC3s) in experimental animals have become an interest for research over recent years. Ethanol-induced liver disease is correlated to impairment of ILC3s in the gut from properly producing IL-22, thus stimulating bacterial translocation. Therefore, by targeting ILC3s and ameliorating bacterial translocation, progressive liver damage could be prevented allowing for immune system to put emphasis the response in the gut. Another therapeutic approach is through the administration of IL-22 producing bacteria which can also reduce bacterial translocation. The first human phase I clinical trial using F-652, a recombinant fusion protein of human IL-22 and immunoglobulin G2 fragment crystallisable in healthy subjects was performed and phase II clinical trial was done to treat patients with alcoholic hepatitis (AH). These patients treated with F-652 revealed a remarkable decrease in the Model for End-Stage Liver Disease (MELD) score, total bilirubin, ALT and AST, a high rate of Lille score, and reduction of marker of inflammation in plasma.

Nutrition-based therapies are alternative therapeutic approach to alcohol-associated liver disease. Supplementation of microbiota derived-metabolites like short-chain fatty acids (SCFAs), medium-chain fatty acids (MCFAs), or long-chain fatty acids (LCFAs) have positive effects on the host, and can act as potential therapies for ameliorating alcohol-associated liver disease. Studies have shown that these agents can reduce liver damage and improve the intestinal gut barrier, while MCFAs and LCFAs, especially have been found to improve the expression of intestinal tight junctions.

Although, several recent studies show potential in advancing treatment towards alcohol-associated liver disease, further research is required to manage the disease. Targeting ILC3s, and Th17 cells functionality along with lipopolysaccharide-associated immune system can act as promising alternative therapeutic approaches. Therefore, continuation of research into these alternative therapies to these targets can enhance understanding of treating diseases affecting gut and liver health.

Source: Bruellman R, Llorente C. A Perspective of Intestinal Immune-Microbiome Interactions In Alcohol-Associated Liver Disease. Int J Biol Sci. 2021;17(1):307-327. Published 2021 Jan 1.