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

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.

Dietary Synbiotic Supplementation Protects Barrier Integrity of Hepatocytes and Liver Sinusoidal Endothelium in a Mouse Model of Chronic-Binge Ethanol Exposure

“…Thus, ethanol-induced gut dysbiosis and subsequent depleted butyrate generation and SCFA transporter expression could compromise the hosts' ability to counteract the harmful effects of LPS on LSEC and hepatocytes. Previously, we found that mice supplemented with butyrate (tributyrin) during chronic-binge ethanol exposure exhibited protection of vascular and endothelial barrier protein expression in the proximal colon [16]. Thus, here we confirmed with an in vitro model the direct beneficial effects of butyrate on endothelial barrier integrity disrupted by ethanol and/or LPS.…”

“…The assay was performed according to the protocol previously described [14,16] Liver sections and HUVEC monolayers underwent immunostaining for proteins expressed by vascular and endothelial cells (vWF, CD31, Type IV Collagen, E-Cadherin, VE-Cadherin, Claudin-5, and β-catenin), macrophages (F4/80), and for the receptor for advanced glycation end-products (RAGE) in the liver. Specific immunofluorescent positive staining was compared to sections incubated with phosphate-buffered saline (PBS) as a negative control; in these studies no positive staining was seen with PBS incubation.…”

Effects of dietary tributyrin on intestinal mucosa development, mitochondrial function and AMPK-mTOR pathway in weaned pigs

“…Several studies reported that tributyrin reduced intestinal oxidative stress in the ethanol-challenged colitis [41] and colon of dextran sodium sulphate-challenged mice [42]. However, there was little evidence about the antioxidant effect of tributyrin in pigs.…”

Suppression of HDAC2 by sodium butyrate alleviates apoptosis of kidney cells in db/db mice and HG‑induced NRK‑52E cells

“…In addition, butyrate can downregulate NADPH oxidase in endothelial cells and consequently decrease the oxidative stress in atherosclerotic lesion sites (31). Oxidative stress in the proximal colon of mice induced by chronic-binge ethanol feeding can also be inhibited by NaBu (32). The present study identified that NaBu suppresses HG-induced oxidative stress, inhibits the level of LDH and elevates the level of SOD in NRK-52E cells.…”