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Liver diseases

Heavily involved in the development of certain liver diseases, the intestinal microbiota may become a major therapeutic target.

Alcohol and obesity, causes of liver disease 

Liver diseases (hepatopathies) present varying degrees of severity, ranging at one extreme from steatosis, which is benign and reversible, to hepatic inflammation (NASH), hepatitis, fibrosis, cirrhosis and, at the other extreme, to hepatocellular carcinoma (liver cancer). Asymptomatic in their less serious forms, liver diseases can present with jaundice, nausea, and fever in their advanced forms.

Alcohol abuse is a known cause of diet-based liver disease (alcoholic liver diseases or ALD), however  excess weight and obesity are less well-known. The metabolic steatosis (or NAFLD) that they cause represents the primary cause of chronic liver diseases in industrialized countries.

Intestinal dysbiosis, cofactor in liver disease

It seems that these risk factors are not enough to induce hepatopathy on their own. The existence of an imbalance in the intestinal microbiota is also involved. The evidence for this is that all patients with liver disease, regardless of the cause, present with dysbiosis and a change in the intestinal barrier. The more serious the liver damage, the more significant the dysbiosis. 

Probiotics, prebiotics, and fecal transplant, three promising avenues for research

Current treatment for liver disease includes lifestyle and diet changes (weight loss and physical activity), with or without associated medical treatments, which can range in complexity (medication, liver transplant). 

The role of the microbiota is now clear, so modifying it with prebiotics, probiotics, and fecal transplant constitutes a promising avenue for preventative and therapeutic research.

 

Sources:

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Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: human gut microbes associated with obesity. Nature. 2006 ; 444 : 1022-3.

Zhu L, Baker SS, Gill C, et al. Characterization of gut microbiomes in nonalcoholic steatohepatitis (NASH) patients: a connection between endogenous alcohol and NASH. Hepatology. 2013 ; 57 : 601-9.

Le Roy T, Llopis M, Lepage P, et al. Intestinal microbiota determines development of non-alcoholic fatty liver disease in mice. Gut. 2013 ; 62 : 1787-94.

Henao-Mejia J, Elinav E, Jin C, et al. Inflammasome mediated dysbiosis regulates progression of NAFLD and obesity. Nature. 2012 ; 482 : 179-85.

Bull-Otterson L, Feng W, Kirpich I, et al. Metagenomic analyses of alcohol induced pathogenic alterations in the intestinal microbiome and the effect of Lactobacillus rhamnosus GG treatment. PLoS One. 2013 ; 8 : e53028.

Yan AW, Fouts DE, Brandl J, et al. Enteric dysbiosis associated with a mouse model of alcoholic liver disease. Hepatology 2011 ; 53 : 96-105.

Szabo G. Gut-liver axis in alcoholic liver disease. Gastroenterology 2015 ; 148 : 30-6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4274189/