Influence of Alcohol on the Intestinal Immune System

Alcohol misuse is associated with disruption of the microbial homeostasis (dysbiosis) and microbial overgrowth in the gut, gut barrier disruption, and translocation of microbes into the systemic circulation. It also induces changes in regulatory mechanisms of the gut, which is the largest peripheral immune organ. The gut-liver axis is important for health and disease, and alterations in the intestinal immune system contribute to alcohol-associated liver disease (ALD). Understanding these changes might help discover new targets for drugs and therapeutic approaches.

A systematic literature search was conducted in PubMed, Medline, and Embase of manuscripts published between January 2000 and November 2023 using the terms ("alcohol" or "ethanol") AND ("immune" or "immunol") AND ("intestine," "colon," or "gut"). Eligible manuscripts included studies and reviews that discussed the effects of ethanol on immune cells in the intestine.

A total of 506 publications were found in the databases on November 20, 2023. After excluding duplicates and research not covering ALD (415 articles), 91 studies were reviewed. Also included were manuscripts covering specific immune cells in the context of ALD.

Balancing immune tolerance vs. initiating an immune response challenges the intestinal immune system. Alcohol induces disruption of the intestinal barrier, which is accompanied by a thicker mucus layer and reduced anti-microbial peptides. This leads to longer attachment of bacteria to epithelial cells and consequently greater translocation into the circulation. Bacterial translocation activates the immune system, reducing the activity of regulatory T cells and inducing T helper 17 response via a variety of pathways. The role of innate immune cells, especially Type 3 innate lymphoid cells, and of specific B- and T-cell subsets in ALD remains elusive. Gut dysbiosis, translocation of viable bacteria and bacterial products into the circulation, and changes in the intestinal barrier have been linked to immune deficiency and infections in patients with cirrhosis. Modifying the intestinal immune system could reduce intestinal inflammation and alcohol-induced liver injury. Understanding the underlying pathophysiology can help to detect new targets for drugs and design therapeutic strategies.