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A Designer Synbiotic Attenuates Chronic-Binge Ethanol-Induced Gut-Liver Injury in Mice

1
Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
2
Department of Pediatrics, Children’s Nutrition Research Center, U.S. Department of Agriculture/Agricultural Research Service, Baylor College of Medicine, Houston, TX 77030, USA
3
Department of Pediatric Gastroenterology, Cleveland Clinic Children’s Hospital, Cleveland, OH 44195, USA
4
Center for Human Nutrition, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH 44195, USA
*
Author to whom correspondence should be addressed.
Nutrients 2019, 11(1), 97; https://doi.org/10.3390/nu11010097
Received: 4 December 2018 / Revised: 21 December 2018 / Accepted: 30 December 2018 / Published: 5 January 2019
(This article belongs to the Special Issue Health Benefits of Fermentation)
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Abstract

Gut dysbiosis and altered short-chain fatty acids are associated with ethanol-induced liver injury. SCFA are fermentation byproducts of the gut microbiota known to have many beneficial biological effects. We tested if a designer synbiotic could protect against ethanol-induced gut-liver injury. C57BL/6 female mice were exposed to chronic-binge ethanol feeding consisting of ethanol (5% vol/vol) for 10 days, followed by a single gavage (5 g/kg body weight) 6 h before euthanasia. A group of mice also received oral supplementation daily with a designer synbiotic, and another group received fecal slurry (FS); control animals received saline. Control mice were isocalorically substituted maltose dextran for ethanol over the entire exposure period. Ethanol exposure reduced expression of tight junction proteins in the proximal colon and induced hepatocyte injury and steatosis. Synbiotic supplementation not only mitigated losses in tight junction protein expression, but also prevented ethanol-induced steatosis and hepatocyte injury. Ethanol exposure also increased hepatic inflammation and oxidative stress, which was also attenuated by synbiotic supplementation. Mice receiving FS were not protected from ethanol-induced liver injury or steatosis. Results were associated with luminal SCFA levels and SCFA transporter expression in the proximal colon and liver. These results indicate supplementation with a designer synbiotic is effective in attenuating chronic-binge ethanol-induced gut-liver injury and steatosis in mice, and highlight the beneficial effects of the gut microbial fermentation byproducts. View Full-Text
Keywords: short chain fatty acids; butyrate; propionate; synbiotic; intestine; liver; inflammation; steatosis; ethanol; tight junction proteins short chain fatty acids; butyrate; propionate; synbiotic; intestine; liver; inflammation; steatosis; ethanol; tight junction proteins
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Roychowdhury, S.; Glueck, B.; Han, Y.; Mohammad, M.A.; Cresci, G.A.M. A Designer Synbiotic Attenuates Chronic-Binge Ethanol-Induced Gut-Liver Injury in Mice. Nutrients 2019, 11, 97.

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