Abstract
Alcoholic liver disease (ALD), a disorder caused by excessive alcohol intake represents a global health care burden. ALD encompasses a broad spectrum of hepatic injuries including asymptomatic steatosis, alcoholic steatohepatitis (ASH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The susceptibility of alcoholic patients to develop ALD is highly variable and its progression to more advanced stages is strongly influenced by several hits (i.e., amount and duration of alcohol abuse). Among them, the intestinal microbiota and its metabolites have been recently identified as paramount in ALD pathophysiology. Ethanol abuse triggers qualitative and quantitative modifications in intestinal flora taxonomic composition, mucosal inflammation, and intestinal barrier derangement. Intestinal hypermeability results in the translocation of viable pathogenic bacteria, Gram-negative microbial products, and pro-inflammatory luminal metabolites into the bloodstream, further corroborating the alcohol-induced liver damage. Thus, the premise of this review is to discuss the beneficial effect of gut microbiota modulation as a novel therapeutic approach in ALD management.
Highlights
Chronic alcohol consumption represents one of the most common causes of mortality worldwide [1]
This review aimed to focus on the relevance of gut microbiota modulation in the development and progression of Alcoholic liver disease (ALD) and its promising role as potential diagnostic strategy and therapeutic target in the personalized ALD management
Alcohol-induced enhanced intestinal permeability and endotoxemia may affect phycological status and cognitive ability, reinforcing the drinking tendency. The proof of this concept has been provided by Leclercq and colleagues who showed that in noncirrhotic patients hospitalized for alcohol detoxification, the increasing intestinal permeability and LPS serum dosage were significantly correlated with higher scores of depression, anxiety, decreased social interactions, and ethanol cravings, even after alcohol withdrawal [70]
Summary
Chronic alcohol consumption represents one of the most common causes of mortality worldwide [1]. The progression of ALD to more advanced conditions is strongly influenced by several issues, i.e., amount and duration of alcohol abuse, age, gender, ethnicity, comorbidities, nutritional status and by environmental, inherited, and epigenetic factors that cause differences in susceptibility to liver damage [9]. The increased gut permeability due to alcohol abuse leads to higher lipopolysaccharide (LPS) concentration into portal blood flow which bind to Toll-like receptor 4 (TLR4) and activate nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) stimulating in turn, pro-inflammatory cytokines release, reactive oxygen species (ROS) production, and oxidative stress All these events may induce the activation of resident macrophages, the Kupffer cells and hepatic stellate cells (HSCs), perpetuating inflammation and fibrosis in the liver [11,12]. This review aimed to focus on the relevance of gut microbiota modulation in the development and progression of ALD and its promising role as potential diagnostic strategy and therapeutic target in the personalized ALD management
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