The role of butyrate in ethanol‐induced intestinal immune responses and associated gut‐liver injury

Abstract

PurposeFollowing a physiologic insult, an immune response needs to be adequately mounted and resolved for proper organ function homeostasis. The immune response to ethanol exposure differs based on multiple factors including the duration of ethanol exposure. While chronic ethanol exposure is proinflammatory, acute ethanol can dampen immune responses. Butyrate, a fermentation byproduct of the gut microbiota, influences gut inflammation and immunity. Our prior work reveals butyrate protects against EtOH‐induced intestinal and hepatic injury. This study aimed to determine butyrate's impact on intestinal innate immune responses following chronic‐binge EtOH exposure.MethodsFemale C57BL/6J age‐matched mice were adapted to a control liquid diet for 5 days, then randomly assigned to a 5% v/v (27% total kcal) ethanol‐containing diet or an isocalorically‐substituted maltose dextrin containing diet for EtOH for 10 days. Ethanol‐fed groups were allowed free access to the diet and control mice were pair‐fed. On day 11, mice were orally gavaged a 5 g/kg dose of EtOH or isocaloric maltose and mice were euthanized 9 hours later. Mice were provided equimolar glycerol or tributyrin (5mM) as part of the liquid diet over the 10 days of EtOH exposure as well as added into the EtOH or maltose gavage at a dose of 2.5 mM. Proximal colon was dissected and mRNA and protein expression of markers of immune and inflammatory response and neovasculature were evaluated.ResultsIn response to chronic‐binge EtOH exposure, genes and proteins for immune and inflammatory mediators had decreased expression in proximal colon including markers for leukocytes, macrophages, neutrophils, cytokines and chemokines. Interestingly, EtOH exposure was also associated with decreased mediators of angiogenesis and markers of vasculature. However, mice co‐treated with tributyrin during EtOH exposure had comparable mRNA and protein expression of several key immune and inflammatory parameters and enhanced makers of angiogenesis as pair‐fed control mice. These preserved responses were associated with protection of intestinal tight junction proteins and liver injury.ConclusionThese findings show tributyrin protected against reduced vasculature and blunted immune responses in the proximal colon caused by chronic‐binge ethanol exposure. These data suggest butyrate could be a potential protective supplement to ethanol consumption and future studies investigating role in human models is warranted.Support or Funding InformationNIH NIAAA R00 ‐ 4R00AA023266‐03This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.