Alcohol decreases intestinal ratio of Lactobacillus to Enterobacteriaceae and induces hepatic immune tolerance in a murine model of DSS-colitis

Gut Microbes. 2020 Nov 9;12(1):1-16. doi: 10.1080/19490976.2020.1838236.

Abstract

Alcohol can potentiate disease in a mouse model of dextran sodium sulfate (DSS) colitis; however, the underlying mechanism remains to be established. In this study, we assessed whether the potentiated disease could be related to Enterobacteriaceae and Lactobacillus, as changes in their relative abundance can impact intestinal health. We also assessed whether the intestinal barrier is compromised after alcohol and DSS as it may increase bacterial translocation and liver inflammation. Mice were administered DSS followed by binge ethanol or water vehicle, generating four experimental groups: (Control+Vehicle, Control+Ethanol, DSS+Vehicle, DSS+Ethanol). DNA was isolated from colon and cecal contents followed by qPCR for levels of Enterobacteriaceae and Lactobacillus. Colon and liver sections were taken for histology. Intestinal epithelial cells were isolated from the colon for RNA expression. DSS+Ethanol cecal contents exhibited a 1 log increase in Enterobacteriaceae (p < .05), a 0.5 log decrease in Lactobacillus, and a 1.5 log decrease (p < .05) in the Lactobacillus:Enterobacteriaceae ratio compared to DSS+Vehicle, with similar trends in colon contents. These changes correlated with shorter colons and more weight loss. Irrespective of ethanol administration, DSS compromised the mucosal barrier integrity, however only DSS+Ethanol exhibited significant increases in circulating endotoxin. Furthermore, the livers of DSS+Ethanol mice had significantly increased levels of triglycerides, mononuclear cells, yet exhibited significantly depressed expression of liver inflammatory pathways, suggestive of tolerance induction, compared to mice receiving DSS+Vehicle. Our results suggest that ethanol after DSS colitis increases the intestinal burden of Enterobacteriaceae which may contribute to intestinal and liver damage, and the induction of immune tolerance.

Keywords: Enterobacteriaceae; Lactobacillus; colitis; ethanol; immune tolerance; inflammation; liver.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bacterial Load
  • Colitis / chemically induced
  • Colitis / immunology*
  • Colitis / microbiology
  • Dextran Sulfate
  • Disease Models, Animal
  • Endotoxins / blood
  • Enterobacteriaceae / isolation & purification*
  • Ethanol / pharmacology*
  • Immune Tolerance / immunology*
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / microbiology
  • Lactobacillus / isolation & purification*
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Tight Junctions / physiology
  • Triglycerides / blood

Substances

  • Endotoxins
  • Triglycerides
  • Ethanol
  • Dextran Sulfate