Abstract

BackgroundNew evidence implies that the imbalance of gut microbiota is associated with the progression of alcoholic liver disease (ALD) and that the composition of gut microbiota is altered in ALD patients. However, the predominant bacterium in patients involved in the progress of ALD has not been identified. The purpose of this study is to investigate the predominant bacterium in the early and end-stages of ALD as well as the relationship between the bacterium and the degree of liver injury.MethodsWe enrolled 21 alcoholic fatty liver (AFL) patients, 17 alcoholic liver cirrhosis (ALC) patients and 27 healthy controls, and sequenced the 16S rRNA gene of their fecal microbiota. The gut microbiota composition and its relationship with the indicators of clinical hepatic function were assessed using canonical correspondence analysis (CCA), spearman correlation heatmap and multivariate association with linear (MaAsLin) Models.ResultsThe composition and structure of gut microbiota changed greatly in different stages of ALD, and the degree of disorder was aggravated with the progression of ALD, even in the early stage. Moreover, the relative abundance of Streptococcus was highly enriched only in patients with ALC (P <0.001), and positively correlated with AST level (P = 0.029). The abundance of Streptococcus distinguished the liver injury of ALC patients from the controls with an area under the receiver-operating characteristic curve (AUC) of 0.877 (P < 0.001).ConclusionsThese findings indicate that the imbalance of gut microbiota exists at the early and end-stages of ALD, and the degree of disorder is aggravated with the progression of ALD. Streptococcus, as the predominant bacterium, may be a microbiological marker to evaluate the severity of liver injury in ALD patients.

Highlights

  • Alcoholic liver disease (ALD) is a chronic liver disease caused by long-term alcohol-use disorder, and its pathological changes include steatosis, steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma (Dunn and Shah, 2016).Worldwide, alcohol-related liver diseases are the leading cause of liver disease-related mortality in most countries (Savolainen et al, 1993; Gao and Bataller, 2011)

  • The patients who met the following criteria were excluded from the study: 1) if the patients were suffering from viral hepatitis, drug hepatitis, autoimmune liver disease or other specific etiology of liver disease, 2) if the patients were suffering from the diseases that confirmed related to microbiome, such as inflammatory bowel disease, gastrointestinal tumors, heart disease, diabetes and so on, 3) if the patients regularly use or recently use specific drugs, which may affect the condition of gut microbiota, such as proton pump inhibitor (PPI), laxatives and so on

  • Analysis of similarities (ANOSIM) was performed based on Bray -Curtis distances (***P < 0.001). It showed that the difference between the groups was greater than that within groups, which indicated that the grouping method, based on the processes of ALD, was effective and meaningful

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Summary

Introduction

Alcoholic liver disease (ALD) is a chronic liver disease caused by long-term alcohol-use disorder, and its pathological changes include steatosis, steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma (Dunn and Shah, 2016).Worldwide, alcohol-related liver diseases are the leading cause of liver disease-related mortality in most countries (Savolainen et al, 1993; Gao and Bataller, 2011). Recent studies have provided evidence that ALD may be related to oxidative stress injury from alcohol metabolism, abnormal methionine metabolism, injury of inflammatory mediators, intestinal microbiota imbalance and bacterial translocation (Shao et al, 2018). As the main product of gut microbiota, short-chain fatty acids (SCFA) have been found to play an important role in lipid turnover and energy homeostasis by reducing adipocyte lipolysis and adipogenesis (Hong et al, 2005). New evidence implies that the imbalance of gut microbiota is associated with the progression of alcoholic liver disease (ALD) and that the composition of gut microbiota is altered in ALD patients. The purpose of this study is to investigate the predominant bacterium in the early and end-stages of ALD as well as the relationship between the bacterium and the degree of liver injury

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