Enteric Dysbiosis Associated with a Mouse Model of Alcoholic Liver Disease
By Arthur W. Yan, Derrick E. Fouts, J. Brandl, P. Starkel, M. Torralba, E. Schott, H. Tsukamoto, Karen E. Nelson, David A. Brenner, B. Schnabl. Hepatology, 2010
742 citations recorded by the source corpus.
The translocation of bacteria and bacterial products into the circulation contributes to alcoholic liver disease. Intestinal bacterial overgrowth is common in patients with alcoholic liver disease. The aims of our study were to investigate bacterial translocation, changes in the enteric microbiome, and its regulation by mucosal antimicrobial proteins in alcoholic liver disease. We used a mouse model of continuous intragastric feeding of alcohol or an isocaloric diet. Bacterial translocation occurred prior to changes observed in the microbiome. Quantitative changes in the intestinal microflora of these animals were assessed first using conventional culture techniques in the small and large intestine. Although we found no difference after 1 day or 1 week, intestinal bacterial overgrowth was observed in the gastrointestinal tract of mice fed alcohol for 3 weeks compared with control mice fed an isocaloric liquid diet. Because <20% of all gastrointestinal bacteria can be cultured using conventional methodologies, we performed massively parallel pyrosequencing to further assess the qualitative changes in the intestinal microbiome following alcohol exposure. Sequencing of 16S ribosomal RNA genes revealed a relative abundance of Bacteroidetes and Verrucomicrobia bacteria in mice fed alcohol compared with a relative predominance of Firmicutes bacteria in control mice. With respect to the host's transcriptome, alcohol feeding was associated with down‐regulation in gene and protein expression of bactericidal c‐type lectins Reg3b and Reg3g in the small intestine. Treatment with prebiotics partially restored Reg3g protein levels, reduced bacterial overgrowth, and lessened alcoholic steatohepatitis. Conclusion: Alcohol feeding is associated with intestinal bacterial overgrowth and enteric dysbiosis. Intestinal antimicrobial molecules are dysregulated following chronic alcohol feeding contributing to changes in the enteric microbiome and to alcoholic steatohepatitis. (HEPATOLOGY 2011)
Subfields: Epidemiology, Molecular Biology, Pathology and Forensic Medicine
View Paper: https://www.semanticscholar.org/paper/c5154754e3e09039272a7ed09439834c21df6e59
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Citations in the corpus
- Kupffer Cells in the Liver (2013, positive): “Increased p38 mitogen-activated protein kinase (MAPK) activity (63), upregulation of miRNA-155 (26) and decreased retinoic acid receptor element binding activity (89) in response to chronic ethanol have all been implicated in the mechanisms for stabilization of TNF-α mRNA in macrophages.”
- The gut microbiota and host health: a new clinical frontier (2015, background): “46 Patients with alcoholic liver disease also show increased gut permeability, allowing translocation of bacteria and bacterial products to the liver.”
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- Characterization of fecal microbial communities in patients with liver cirrhosis (2011, result): “However, it has been shown in previous animal model studies that chronic alcohol consumption can affect gut bacterial composition.(41,42) In this study, Prevotellaceae was enriched in alcoholic cirrhosis patients when compared with HBV-related cirrhosis patients and controls.”
- Pathological bacterial translocation in liver cirrhosis. (2014, background): “In addition, down-regulation of regenerating isletderived proteins (RegIIIb and RegIIIc) has been demonstrated in the small intestine of mice as well as humans after chronic alcohol intake [53].”
- Intestinal permeability, gut-bacterial dysbiosis, and behavioral markers of alcohol-dependence severity (2014, background): “Preclinical studies have shown that chronic ethanol administration induces in rats a dysbiosis (45), and in mice a decrease in the level of Ruminococcaceae (46), or a decrease in the level of Firmicutes and an increase in Bacteroidetes (47).”