Tributyrin Supplementation Protects Immune Responses and Vasculature and Reduces Oxidative Stress in the Proximal Colon of Mice Exposed to Chronic-Binge Ethanol Feeding.

B Glueck,Y Han,G A M Cresci

doi:10.1155/2018/9671919

Abstract

Excessive ethanol consumption causes adverse effects and contributes to organ dysfunction. Ethanol metabolism triggers oxidative stress, altered immune function, and gut dysbiosis. The gut microbiome is known to contribute to the maintenance of intestinal homeostasis, and disturbances are associated with pathology. A consequence of gut dysbiosis is also alterations in its metabolic and fermentation byproducts. The gut microbiota ferments undigested dietary polysaccharides to yield short-chain fatty acids, predominantly acetate, propionate, and butyrate. Butyrate has many biological mechanisms of action including anti-inflammatory and immunoprotective effects, and its depletion is associated with intestinal injury. We previously showed that butyrate protects gut-liver injury during ethanol exposure. While the intestine is the largest immune organ in the body, little is known regarding the effects of ethanol on intestinal immune function. This work is aimed at investigating the effects of butyrate supplementation, in the form of the structured triglyceride tributyrin, on intestinal innate immune responses and oxidative stress following chronic-binge ethanol exposure in mice. Our work suggests that tributyrin supplementation preserved immune responses and reduced oxidative stress in the proximal colon during chronic-binge ethanol exposure. Our results also indicate a possible involvement of tributyrin in maintaining the integrity of intestinal villi vasculature disrupted by chronic-binge ethanol exposure.

Highlights

Excessive ethanol consumption causes damage to various organs and systems
The following are primary antibodies: antigranulocye colonystimulating factor (G-CSF), anti-Von Willebrand factor, and leukocyte common antigen, CD45 (Clone I3/ 2.3), came from Abcam (Cambridge, MA); anti-neutrophil (NIMP14) antibody came from Novus Biologicals (Littleton, CO); C3b/iC3b/C3c (C3b) came from Hycult Biotechnology (Uden, Netherlands); anticluster of differentiation, CD68, was from AbD Serotec (Raleigh, NC); and antiplatelet endothelial cell adhesion molecule (PECA1)/CD31 was from Genetex (Irvine, CA)
Mice exposed to ethanol for 10 days followed by a single ethanol gavage and euthanized 9 hours later exhibited less positive staining of markers of innate immunity (CD45, CD68, C3b, and NIMPR14) (Figures 1(a), 1(b), 1(f), and 1(g)) and decreased messenger RNA (mRNA) expression of macrophages (CD68, lymphocyte antigen 6 complex (Ly6c)) (Figures 1(c) and 1(d)) in the proximal colon

Summary

Introduction

Excessive ethanol consumption causes damage to various organs and systems. While the liver is the primary target of ethanol’s detrimental effects, the brain, pancreas, lungs, intestine, and the immune system are known to be affected. Ethanol promotes the generation of superoxide anion and hydrogen peroxide, and these byproducts contribute to endothelial dysfunction, vasoconstriction, and hypertension [2]. Both acute ethanol and chronic ethanol interfere with multiple aspects of innate immune responses resulting in chronic alcoholics having an increased risk and severity of infections. This association has been demonstrated with several types of infections including pulmonary [3], hepatitis C [4], and human immunodeficiency virus [5]. Ethanol impairs natural killer cell activity, decreasing their ability to destroy their target cells [9, 10]

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