Chronic ethanol consumption alters intestinal microbiota composition (MUC9P.746)

It is well known that chronic alcohol consumption leads to organ damage and increased susceptibility to bacterial and viral infections. Ethanol exposure in the intestinal lumen alters tight junction proteins leading to disruption of the epithelial barrier. Increased permeability in turn leads to translocation of gut-derived endotoxins causing inflammatory responses in the liver that contribute to alcoholic liver disease. Recent studies have shown that gut mucosa homeostasis is also modulated by the microbiome. Disruptions in the gut microbiome have been described for many diseases including IBD, diabetes and colon cancer. In order to gain a better understanding of the dose-dependent effects of ethanol on the gut microbiome, we performed ribosomal RNA sequencing to determine the differentially expressed bacteria in the small and large intestine in a rhesus macaque model of voluntary ethanol self-administration. In the colon we observed a 2-fold increase in heavy drinkers compared to nondrinkers in the phylum Bacteroidetes that subsequently results in a decrease in Firmicutes, the phylum containing most beneficial lactic acid bacteria. In the duodenum, jejunum, ileum and colon we found a 3-fold decrease in the commensal species Lactobacillus intestinalis and a 2-fold increase in the potential pathogenic species Prevotella copri in heavy drinkers compared to nondrinkers. These studies are likely to reveal mechanisms of ethanol-related gut dysregulation and related inflammation.