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The Therapeutic Implications of the Gut Microbiome and Probiotics in Patients with NAFLD
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Role of Gut Dysbiosis in Liver Diseases: What Have We Learned So Far?

Department of Gastroenterology, Nara Medical University, Kashihara 634-8522, Japan
Diseases 2019, 7(4), 58; https://doi.org/10.3390/diseases7040058
Received: 13 October 2019 / Revised: 29 October 2019 / Accepted: 29 October 2019 / Published: 12 November 2019
(This article belongs to the Special Issue Gut Microbiome and Human Diseases)
Accumulating evidence supports that gut dysbiosis may relate to various liver diseases. Alcoholics with high intestinal permeability had a decrease in the abundance of Ruminnococcus. Intestinal dysmotility, increased gastric pH, and altered immune responses in addition to environmental and genetic factors are likely to cause alcohol-associated gut microbial changes. Alcohol-induced dysbiosis may be associated with gut barrier dysfunction, as microbiota and their products modulate barrier function by affecting epithelial pro-inflammatory responses and mucosal repair functions. High levels of plasma endotoxin are detected in alcoholics, in moderate fatty liver to advanced cirrhosis. Decreased abundance of Faecalibacterium prausnitzii, an anti-inflammatory commensal, stimulating IL-10 secretion and inhibiting IL-12 and interferon-γ expression. Proteobacteria, Enterobacteriaceae, and Escherichia were reported to be increased in NAFLD (nonalcoholic fatty liver disease) patients. Increased abundance of fecal Escherichia to elevated blood alcohol levels in these patients and gut microbiota enriched in alcohol-producing bacteria produce more alcohol (alcohol hypothesis). Some undetermined pathological sequences related to gut dysbiosis may facilitate energy-producing and proinflammatory conditions for the progression of NAFLD. A shortage of autochthonous non-pathogenic bacteria and an overgrowth of potentially pathogenic bacteria are common findings in cirrhotic patients. The ratio of the amounts of beneficial autochthonous taxa (Lachnospiraceae + Ruminococaceae + Veillonellaceae + Clostridiales Incertae Sedis XIV) to those of potentially pathogenic taxa (Enterobacteriaceae + Bacteroidaceae) was low in those with early death and organ failure. Cirrhotic patients with decreased microbial diversity before liver transplantation were more likely to develop post-transplant infections and cognitive impairment related to residual dysbiosis. Patients with PSC had marked reduction of bacterial diversity. Enterococcus and Lactobacillus were increased in PSC patients (without liver cirrhosis.) Treatment-naive PBC patients were associated with altered composition and function of gut microbiota, as well as a lower level of diversity. As serum anti-gp210 antibody has been considered as an index of disease progression, relatively lower species richness and lower abundance of Faecalibacterium spp. in gp210-positive patients are interesting. The dysbiosis-induced altered bacterial metabolites such as a hepatocarcinogenesis promotor DCA, together with a leaky gut and bacterial translocation. Gut protective Akkermansia and butyrate-producing genera were decreased, while genera producing-lipopolysaccharide were increased in early hepatocellular carcinoma (HCC) patients. View Full-Text
Keywords: gut dysbiosis; alcoholic liver injury; non-alcoholic fatty liver disease; liver cirrhosis; liver transplantation; primary sclerosing cholangitis; primary biliary cholangitis; hepatocellular carcinoma gut dysbiosis; alcoholic liver injury; non-alcoholic fatty liver disease; liver cirrhosis; liver transplantation; primary sclerosing cholangitis; primary biliary cholangitis; hepatocellular carcinoma
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Fukui, H. Role of Gut Dysbiosis in Liver Diseases: What Have We Learned So Far? Diseases 2019, 7, 58.

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