2.3.1. Alcoholic Liver Disease

In alcoholic fatty liver disease, viable bacteria, endotoxin, and LPS have been observed in the blood of both animal models and ALD patients, for which there are many potential mechanisms [49,50]. Small intestinal bacterial overgrowth (SIBO) in chronic alcoholics is more prevalent than healthy controls [51], perhaps due to extended orocaecal transit time in alcoholics compared to social drinkers [52]. SIBO has been suggested to mediate translocation due to differences in mucosal defense in the small intestine, primarily a reduction in mucus secretion. Increased intestinal permeability has also been reported in alcoholic cirrhosis, ALD, and even in non-cirrhotic alcoholics using in vivo assays [53–55].

In human studies, a reduction in the number of small intestinal villi, goblet cells, and TJ protein ZO-1 expression in the colon were observed in chronic alcoholics [56–58]. Furthermore, cell culture and animal studies suggest that ethanol and its metabolite, acetaldehyde, can alter intestinal barrier function by (1) inducing epithelial cell apoptosis, (2) disrupting TJs by downregulating ZO-1, occludin, and claudin and redistributing ZO-1 into cytoplasm, and (3) displacing the cytoplasmic skeleton [59–62].

Lastly, the production of intestinal IgA and the quantity of immune cells have been shown to be significantly altered in cases of chronic alcohol consumption and in ALD patients. While systematic IgA is increased in alcoholic liver diseases due to intestinal permeability, fecal IgA and IgA-producing B cells within the lamina propria are reduced in animal models of ALD [63,64]. Recently, a significant decrease in the number and activation state of mucosa-associated invariant T (MAIT) cells, a key component in antibacterial immune defense, was shown in ALD patients [65].
