Abstract
Although alcohol feeding produces evident intestinal microbial changes in animals, only some alcoholics show evident intestinal dysbiosis, a decrease in Bacteroidetes and an increase in Proteobacteria. Gut dysbiosis is related to intestinal hyperpermeability and endotoxemia in alcoholic patients. Alcoholics further exhibit reduced numbers of the beneficial Lactobacillus and Bifidobacterium. Large amounts of endotoxins translocated from the gut strongly activate Toll-like receptor 4 in the liver and play an important role in the progression of alcoholic liver disease (ALD), especially in severe alcoholic liver injury. Gut microbiota and bacterial endotoxins are further involved in some of the mechanisms of nonalcoholic fatty liver disease (NAFLD) and its progression to nonalcoholic steatohepatitis (NASH). There is experimental evidence that a high-fat diet causes characteristic dysbiosis of NAFLD, with a decrease in Bacteroidetes and increases in Firmicutes and Proteobacteria, and gut dysbiosis itself can induce hepatic steatosis and metabolic syndrome. Clinical data support the above dysbiosis, but the details are variable. Intestinal dysbiosis and endotoxemia greatly affect the cirrhotics in relation to major complications and prognosis. Metagenomic approaches to dysbiosis may be promising for the analysis of deranged host metabolism in NASH and cirrhosis. Management of dysbiosis may become a cornerstone for the future treatment of liver diseases.
Highlights
Human microbiota is estimated to contain as many as 1014 bacterial cells, which is a number 10 times greater than the human cells present in our bodies [1,2]
The human gut microbiota is dominated by the Bacteroidetes and the Firmicutes, whereas Proteobacteria, Verrucomicrobia, Actinobacteria, Fusobacteria, and Cyanobacteria are present in minor proportions [2,3]
Their analysis further revealed that the total amount of bacteria and those belonging to the Ruminococcaceae family, especially Faecalibacterium prausnitzii, were negatively correlated to intestinal permeability (IP), while the genera Dorea and Blautia were positively correlated with IP
Summary
Human microbiota is estimated to contain as many as 1014 bacterial cells, which is a number 10 times greater than the human cells present in our bodies [1,2]. The microbiota contributes to digestion, synthesis of vitamins, and resistance to intestinal colonization by pathogens, and contains potentially pathogenic bacteria [6]. Intestinal bacterial overgrowth, changes in intestinal microbiota and the translocation of bacteria and their products are important common pathways for the development and progression of alcoholic liver disease, nonalcoholic fatty liver disease and liver cirrhosis. Their great impacts on the host lead to variable host reactions, which act bidirectionally to maintain the homeostasis on one side and to promote the liver disease on the other side. I would like to overview the roles of gut microbiota and host reaction in the process of alcoholic liver disease, nonalcoholic steatohepatitis, and liver cirrhosis
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