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

Abstract 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 de...

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Autores principales:	Pradeep K. Shukla, Avtar S. Meena, Kesha Dalal, Cherie Canelas, Geetha Samak, Joseph F. Pierre, RadhaKrishna Rao
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/304997ec2f5647b2bec70ae4b0fe8f33
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spelling	oai:doaj.org-article:304997ec2f5647b2bec70ae4b0fe8f332021-12-02T14:01:22ZChronic stress and corticosterone exacerbate alcohol-induced tissue injury in the gut-liver-brain axis10.1038/s41598-020-80637-y2045-2322https://doaj.org/article/304997ec2f5647b2bec70ae4b0fe8f332021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80637-yhttps://doaj.org/toc/2045-2322Abstract 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.Pradeep K. ShuklaAvtar S. MeenaKesha DalalCherie CanelasGeetha SamakJoseph F. PierreRadhaKrishna RaoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Pradeep K. Shukla Avtar S. Meena Kesha Dalal Cherie Canelas Geetha Samak Joseph F. Pierre RadhaKrishna Rao Chronic stress and corticosterone exacerbate alcohol-induced tissue injury in the gut-liver-brain axis
description	Abstract 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.
format	article
author	Pradeep K. Shukla Avtar S. Meena Kesha Dalal Cherie Canelas Geetha Samak Joseph F. Pierre RadhaKrishna Rao
author_facet	Pradeep K. Shukla Avtar S. Meena Kesha Dalal Cherie Canelas Geetha Samak Joseph F. Pierre RadhaKrishna Rao
author_sort	Pradeep K. Shukla
title	Chronic stress and corticosterone exacerbate alcohol-induced tissue injury in the gut-liver-brain axis
title_short	Chronic stress and corticosterone exacerbate alcohol-induced tissue injury in the gut-liver-brain axis
title_full	Chronic stress and corticosterone exacerbate alcohol-induced tissue injury in the gut-liver-brain axis
title_fullStr	Chronic stress and corticosterone exacerbate alcohol-induced tissue injury in the gut-liver-brain axis
title_full_unstemmed	Chronic stress and corticosterone exacerbate alcohol-induced tissue injury in the gut-liver-brain axis
title_sort	chronic stress and corticosterone exacerbate alcohol-induced tissue injury in the gut-liver-brain axis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/304997ec2f5647b2bec70ae4b0fe8f33
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Chronic stress and corticosterone exacerbate alcohol-induced tissue injury in the gut-liver-brain axis

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