Synbiotics Alleviate Hepatic Damage, Intestinal Injury and Muscular Beclin-1 Elevation in Rats after Chronic Ethanol Administration.

Qian Xiao,Suh-Ching Yang,Wan-Chun Chiu,Hitoshi Shirakawa,Ya-Ling Chen,Yi-Hsiu Chen

doi:10.3390/ijms222212547

Abstract

The purpose of this study was to investigate the beneficial effects of synbiotics on liver damage, intestinal health, and muscle loss, and their relevance in rats with chronic ethanol feeding. Thirty Wistar rats fed with a control liquid diet were divided into control and synbiotics groups, which were respectively provided with water or synbiotics solution (1.5 g/kg body weight/day) for 2 weeks. From the 3rd to 8th week, the control group was divided into a C group (control liquid diet + water) and an E group (ethanol liquid diet + water). The synbiotics group was separated in to three groups, SC, ASE, and PSE. The SC group was given a control liquid diet with synbiotics solution; the ASE group was given ethanol liquid diet with synbiotics solution, and the PSE group was given ethanol liquid diet and water. As the results, the E group exhibited liver damage, including increased AST and ALT activities, hepatic fatty changes, and higher CYP2E1 expression. Intestinal mRNA expressions of occludin and claudin-1 were significantly decreased and the plasma endotoxin level was significantly higher in the E group. In muscles, beclin-1 was significantly increased in the E group. Compared to the E group, the PSE and ASE groups had lower plasma ALT activities, hepatic fatty changes, and CYP2E1 expression. The PSE and ASE groups had significantly higher intestinal occludin and claudin-1 mRNA expressions and lower muscular beclin-1 expression when compared to the E group. In conclusion, synbiotics supplementation might reduce protein expression of muscle protein degradation biomarkers such as beclin-1 in rats with chronic ethanol feeding, which is speculated to be linked to the improvement of intestinal tight junction and the reduction of liver damage.

Highlights

The World Health Organization (WHO) reported that 3 million deaths each year were associated with the harmful use of alcohol [1]
Gut barrier dysfunction is linked to the damage of tight junction proteins, such as occludin, claudins, and zonula occludens (ZOs) [5]
It was found that messenger (m)RNA expressions of tight junction proteins were decreased after alcohol treatment both in animal and cell culture studies [6,7]

Summary

Introduction

The World Health Organization (WHO) reported that 3 million deaths each year were associated with the harmful use of alcohol [1]. Around 40~60% of patients with alcoholic liver disease (ALD) suffer from severe sarcopenia [2,3]. Chronic alcohol intake induces dysfunction of the gut barrier and dysbiosis of the gut microbiota which might lead to endotoxemia which might induce muscle loss because of increasing protein degradation in [4]. It was found that messenger (m)RNA expressions of tight junction proteins were decreased after alcohol treatment both in animal and cell culture studies [6,7]. The gut microbiota composition was turned into a composition of pathogenic bacteria accompanied by a decrease in bacterial diversity in rats chronically fed with alcohol [8,9,10]. It was demonstrated that hyperammonemia could be one of several potential reasons for abnormal muscle protein metabolism in ALD patients [12]

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Discussion

Conclusion