Alcohol, the gut microbiome, and liver disease

Abstract

The microorganisms inhabiting our gastrointestinal tract are critical for human health. Chronic heavy alcohol use can modulate the composition and function of the gut microbiota, thereby exacerbating end-organ damage via the gut-brain axis and the gut-liver axis. In this review, we summarize the bacterial, fungal, and viral gut microbial compositional changes associated with alcohol use and alcohol-associated liver disease and discuss the mechanisms of action by which gut dysbiosis reinforces alcohol use behavior and liver inflammation and injury. We also highlight important pre-clinical and clinical trials that target gut microbial-specific mechanisms for the treatment of alcohol use disorder and alcohol-associated liver disease.

Adolescent intermittent ethanol (AIE) produces lasting, sex-specific changes in rat body fat independent of changes in white blood cell composition

“…In addition, alcohol delivered directly into the stomach via gavage could directly alter gut microflora in a manner distinct from vapor exposure models. Alcohol has been shown to contribute to dysbiosis of the gut microbiome ( Jew and Hsu, 2023 ) which can increase endotoxin release and heighten peripheral inflammation. This difference between models could readily change cytokine levels both during developmental exposure as well as in response to adult challenge.…”

Melatonin Prevents Alcohol- and Metabolic Dysfunction- Associated Steatotic Liver Disease by Mitigating Gut Dysbiosis, Intestinal Barrier Dysfunction, and Endotoxemia

“…Acetaldehyde, a highly reactive aldehyde produced during oxidative ethanol metabolism, can increase permeability in the intestinal barrier by disrupting the distribution and organization of tight junction and adherens junction (TJ/AJ) proteins in the intestines [25]. Alcohol (ethanol) also changes the composition of the microbiome in ALD [31,[42][43][44][45], even at the early stages of ALD, causing dysbiosis and bacterial translocation [45]. Even AUD patients exhibit microbial characteristics such as upregulation of GABA metabolism pathways that could serve as intestinal fingerprint biomarkers with a 93% accuracy [29,46].…”

Tributyrin Supplementation Rescues Chronic–Binge Ethanol-Induced Oxidative Stress in the Gut–Lung Axis in Mice

“…The gut microbiome comprises trillions of microbes, and in the past several years there has been an increasing appreciation regarding the important role the gut microbiome plays in supporting health. While there is intra-individual variability (alpha-diversity) in microbiome composition amongst healthy individuals, distinct dissimilarity (beta-diversity) between healthy individuals and those with various chronic diseases is noted [1]. At the phylum level, about 90% of the gut microbiome composition of a healthy individual comprises the Bacteroidetes and Firmicutes phyla.…”

“…Chronic heavy alcohol exposure is known to disrupt the gut microbiome's composition and function, increase intestinal permeability, and activate systemic inflammatory pathways [1]. Chronic alcohol exposure reduces the abundance of Bacteroidetes and Firmicutes phyla, expands the Proteobacteria phylum, and lowers fecal SCFA levels, including that of butyrate [5].…”