title: Gut microbiome and nonalcoholic fatty liver diseases.
abstract: We review recent findings and hypotheses on the roles of gut microbiome in the pathogenesis of nonalcoholic fatty liver diseases (NAFLD). Microbial metabolites and cell components contribute to the development of hepatic steatosis and inflammation, key components of nonalcoholic steatohepatitis (NASH), the severe form of NAFLD. Altered gut microbiome can independently cause obesity, the most important risk factor for NAFLD. This capability is attributed to short-chain fatty acids (SCFAs), major gut microbial fermentation products. SCFAs account for a large portion of caloric intake of the host, and they enhance intestinal absorption by activating GLP-2 signaling. However, elevated SCFAs may be an adaptive measure to suppress colitis, which could be a higher priority than imbalanced calorie intake. The microbiome of NASH patients features an elevated capacity for alcohol production. The pathomechanisms for alcoholic steatohepatitis may apply to NASH. NAFLD/NASH is associated with elevated Gram-negative microbiome and endotoxemia. However, many NASH patients exhibited normal serum endotoxin indicating that endotoxemia is not required for the pathogenesis of NASH. These observations suggest that microbial intervention may benefit NAFLD/NASH patients. However, very limited effects were observed using traditional probiotic species. Novel probiotic therapy based on NAFLD/NASH specific microbial composition represents a promising future direction.
authors.affiliation: Department of Pediatrics, Women and Children's Hospital of Buffalo, Digestive Diseases and Nutrition Center, The State University of New York at Buffalo, Buffalo, New York.
authors.forename: Lixin
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Pediatrics, Women and Children's Hospital of Buffalo, Digestive Diseases and Nutrition Center, The State University of New York at Buffalo, Buffalo, New York.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Baker
authors.affiliation: Department of Pediatrics, Women and Children's Hospital of Buffalo, Digestive Diseases and Nutrition Center, The State University of New York at Buffalo, Buffalo, New York.
authors.forename: Susan S
authors.initials: SS
authors.lastname: Baker
mesh_terms: D000431:Ethanol / Q000378:metabolism; D005232:Fatty Acids, Volatile / Q000378:metabolism*; D041981:Gastrointestinal Tract / Q000382:microbiology*; D006801:Humans; D064307:Microbiota; D008954:Models, Biological; D065626:Non-alcoholic Fatty Liver Disease / Q000382:microbiology* / Q000503:physiopathology*; D009765:Obesity / Q000382:microbiology*
chemical_list: D005232:Fatty Acids, Volatile; D000431:Ethanol