Changes in gut microbiome correlate with intestinal barrier dysfunction and inflammation following a 3-day ethanol exposure in aged mice

• Published in: Alcohol (Fayetteville, N.Y.) Vol. 107; pp. 136 - 143
• Main Authors: McMahan, Rachel H., Hulsebus, Holly J., Najarro, Kevin M., Giesy, Lauren E., Frank, Daniel N., Kovacs, Elizabeth J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2023; Elsevier Limited
• Subjects: Age groups; Aging; Alcohol use; alpha-Defensins - genetics; alpha-Defensins - immunology; Animals; Antimicrobial agents; antimicrobial peptide; Antimicrobial peptides; Antimicrobial Peptides - genetics; Antimicrobial Peptides - immunology; Baby boomers; Chronic illnesses; Cytokines - immunology; Digestive system; Drinking behavior; Dysbacteriosis; Dysbiosis - chemically induced; Dysbiosis - genetics; Dysbiosis - immunology; Dysbiosis - microbiology; Ethanol; Ethanol - pharmacology; Ethanol - toxicity; Feces; Gastrointestinal Microbiome - drug effects; Gastrointestinal Microbiome - genetics; Gastrointestinal Microbiome - immunology; Gastrointestinal tract; Gene expression; Inflammation; Inflammation - chemically induced; Inflammation - genetics; Inflammation - immunology; Inflammation - microbiology; innate immunity; Intestinal microflora; Intestine; Intestines - drug effects; Intestines - immunology; Intestines - microbiology; Liver; Mice; Mice, Inbred C57BL; microbiome; Microbiomes; Microbiota; Morbidity; Older people; Permeability; Permeability - drug effects; Small intestine; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - immunology; intestine; aging; innate immunity; antimicrobial peptide; liver; microbiome
• ISSN: 0741-8329; 1873-6823
• DOI: 10.1016/j.alcohol.2022.08.011

Alcohol use among older adults is on the rise. This increase is clinically relevant as older adults are at risk for increased morbidity and mortality from many alcohol-related chronic diseases compared to younger patients. However, little is known regarding the synergistic effects of alcohol and age. There are intriguing data suggesting that aging may lead to impaired intestinal barrier integrity and dysbiosis of the intestinal microbiome, which could increase susceptibility to alcohol's negative effects. To study the effects of alcohol in age we exposed aged and young mice to 3 days of moderate ethanol and evaluated changes in gut parameters. We found that these levels of drinking do not have obvious effects in young mice but cause significant alcohol-induced gut barrier dysfunction and expression of the pro-inflammatory cytokine TNFα in aged mice. Ethanol-induced downregulation of expression of the gut-protective antimicrobial peptides Defa-rs1, Reg3b, and Reg3g was observed in aged, but not young mice. Analysis of the fecal microbiome revealed age-associated shifts in microbial taxa, which correlated with intestinal and hepatic inflammatory gene expression. Taken together, these data demonstrate that age drives microbiome dysbiosis, while ethanol exposure in aged mice induces changes in the expression of antimicrobial genes important for separating these potentially damaging microbes from the intestinal lumen. These changes highlight potential mechanistic targets for prevention of the age-related exacerbation of effects of ethanol on the gut. •Aged mice display increased sensitivity to the gastrointestinal effects of ethanol.•Three days of ethanol binge increase intestinal barrier dysfunction and TNFα expression in aged, but not young mice.•Ethanol exposure in aged mice induces downregulation of intestinal antimicrobial peptides.•Age-specific changes in the fecal microbiome correlate with altered expression of cytokines and antimicrobial peptides.