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

Sanjoy Roychowdhury,Gail A. M. Cresci,Mahmoud Ali Mohammad,Yingchun Han,Bryan Glueck

doi:10.3390/nu11010097

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.

Highlights

Excessive alcohol consumption can lead to alcoholic liver disease (ALD), liver manifestations that may progress through a series of pathologies starting with fatty liver, or hepatic steatosis
This study aimed to evaluate the effects of supplementing a novel designer synbiotic, comprised of a butyrate-producing bacteria (Faecalibacterium prausnitzii) and a butyrate-yielding prebiotic, on mitigating chronic-binge ethanol-induced gut-liver injury and inflammation in mice
While there was a trend towards an increased percentage percentage of of acetate acetate in in the the ethanol-saline ethanol-saline treated treated animals, animals, this this group group had had lower lower amounts amounts increased of propionate, propionate, pyruvate, pyruvate, and and lactate lactate compared compared to to the the ethanol ethanol treated treated animals animals supplemented supplemented with with the the of synbiotic (Figure (Figure 1)

Summary

Introduction

Excessive alcohol consumption can lead to alcoholic liver disease (ALD), liver manifestations that may progress through a series of pathologies starting with fatty liver, or hepatic steatosis. In a subset of people, hepatic steatosis can proceed to steatohepatitis, characterized by inflammation and hepatic cell death. Steatohepatitis can further proceed to fibrosis, eventually leading to cirrhosis, which encompasses massive hepatocellular injury [1]. Ethanol enters the liver from the intestine through the portal circulation. Expressing high levels of two enzymes which oxidize ethanol, alcohol dehydrogenase and cytochrome. P 450 2E1 (CYP2E1), the liver is the primary site of ethanol metabolism [2]. Ethanol oxidation leads to Nutrients 2019, 11, 97; doi:10.3390/nu11010097 www.mdpi.com/journal/nutrients

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