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Liver Update: Modulation of Gut Microbiota: A promising therapeutics in Alcoholic liver disease

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eMediNexus    09 May 2021

Alcoholic liver disease (ALD) poses a significant health care burden and is caused by excessive alcohol consumption. ALD has a broad spectrum of hepatic injuries including asymptomatic steatosis, alcoholic steatohepatitis (ASH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). There is huge variation in susceptibility of alcoholic patients to develop ALD and its progression to more advanced stages is remarkably affected by several factors such as amount and duration of alcohol abuse. Among these factors, the intestinal microbiota and its metabolites have been recently recognized as important in ALD pathophysiology. Alcohol or ethanol abuse triggers qualitative and quantitative alterations in intestinal flora taxonomic composition, mucosal inflammation, and intestinal barrier derangement. Intestinal hypermeability causes the translocation of viable pathogenic bacteria, Gram-negative microbial products, and pro-inflammatory luminal metabolites into the bloodstream, which in turn, exacerbating the alcohol-induced liver damage. 

The aim of the current standards of care for the management of ALD patients is to prevent either liver damage onset or progression to its severe forms by promoting alcohol abstinence. Nevertheless, the effectivity of treatment is highly dependent from disease severity and the potential to overcome alcohol withdrawal with the help of psychological and pharmacological approaches. The success of these approaches rates between 20–40% of remission success. However, data suggest that the burden of alcohol-related deaths and disabilities is estimated to be 3.8% and 4.6%, respectively, and most of these are attributed to alcoholic cirrhosis and liver failure, annually.

Although liver transplantation, until now is the potential lifesaving indication for the end-stage of liver disease in ALD patients, this treatment option is regarded as a self-inflicted disease and poses limitation due to the ever-increasing demand of donor organs combined with alcohol relapse and cravings. Thus, it is imperative need to develop novel therapeutic interventions for the management of ALD.

Several pre-clinical and human studies have explored the effect of alcohol-induced gut microbiota alterations in the progression of liver disease; however, their mechanism remains still unclear. The main reason behind the intervention of gut microbiota therapies is the positive association between ethanol-induced microbiota unbalancing in the GIT, bacterial overgrowth and development of liver pathology. Hence, rigorous efforts have been used to examine the potential therapeutic strategies that have the potential to modulate intestinal bacteria composition via 1) untargeted approaches, including diet, probiotics, prebiotics, antibiotics, fecal microbiota transplant (FMT) or 2) precision medicine by selectively targeting microbial and host metabolites. 

Source: Meroni M, Longo M, Dongiovanni P. Alcohol or Gut Microbiota: Who Is the Guilty?. Int J Mol Sci. 2019;20(18):4568. Published 2019 Sep 14. 

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