Chronic stress and corticosterone exacerbate alcohol-induced tissue injury in the gut-liver-brain axis

Alcohol use disorders are associated with altered stress responses, but the impact of stress or stress hormones on alcohol-associated tissue injury remain unknown. We evaluated the effects of chronic restraint stress on alcohol-induced gut barrier dysfunction and liver damage in mice. To determine w...

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Bibliographic Details
Published in:Scientific reports 2021-01, Vol.11 (1), p.826-826, Article 826
Main Authors: Shukla, Pradeep K., Meena, Avtar S., Dalal, Kesha, Canelas, Cherie, Samak, Geetha, Pierre, Joseph F., Rao, RadhaKrishna
Format: Article
Language:English
Subjects:
692/4020/2199
692/4020/2741/278/1390
Acetaldehyde
Alcohol
Alcohols
Brain injury
Chemokines
Corticosterone
Cytokines
Digestive system
Endotoxemia
Ethanol
Gastrointestinal tract
Hormones
Humanities and Social Sciences
Inflammation
Intestinal microflora
Intestine
Liver
Liver diseases
Metagenomics
Microbiota
Mucosa
multidisciplinary
Ribonucleic acid
RNA
Science
Science (multidisciplinary)
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Summary:Alcohol use disorders are associated with altered stress responses, but the impact of stress or stress hormones on alcohol-associated tissue injury remain unknown. We evaluated the effects of chronic restraint stress on alcohol-induced gut barrier dysfunction and liver damage in mice. To determine whether corticosterone is the stress hormone associated with the stress-induced effects, we evaluated the effect of chronic corticosterone treatment on alcoholic tissue injury at the Gut-Liver-Brain (GLB) axis. Chronic restraint stress synergized alcohol-induced epithelial tight junction disruption and mucosal barrier dysfunction in the mouse intestine. These effects of stress on the gut were reproduced by corticosterone treatment. Corticosterone synergized alcohol-induced expression of inflammatory cytokines and chemokines in the colonic mucosa, and it potentiated the alcohol-induced endotoxemia and systemic inflammation. Corticosterone also potentiated alcohol-induced liver damage and neuroinflammation. Metagenomic analyses of 16S RNA from fecal samples indicated that corticosterone modulates alcohol-induced changes in the diversity and abundance of gut microbiota. In Caco-2 cell monolayers, corticosterone dose-dependently potentiated ethanol and acetaldehyde-induced tight junction disruption and barrier dysfunction. These data indicate that chronic stress and corticosterone exacerbate alcohol-induced mucosal barrier dysfunction, endotoxemia, and systemic alcohol responses. Corticosterone-mediated promotion of alcohol-induced intestinal epithelial barrier dysfunction and modulation of gut microbiota may play a crucial role in the mechanism of stress-induced promotion of alcohol-associated tissue injury at the GLB axis.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-020-80637-y