title: Cirrhosis, bile acids and gut microbiota: unraveling a complex relationship.
abstract: A picture is now starting to emerge regarding the liver-bile acid-microbiome axis. Increasing levels of the primary bile acid cholic acid (CA) causes a dramatic shift toward the Firmicutes, particularly Clostridium cluster XIVa and increasing production of the harmful secondary bile acid deoxycholic acid (DCA). During progression of cirrhosis, the microbiome, both through their metabolism, cell wall components (LPS) and translocation lead to inflammation. Inflammation suppresses synthesis of bile acids in the liver leading to a positive-feedback mechanism. Decrease in bile acids entering the intestines appears to favor overgrowth of pathogenic and pro-inflammatory members of the microbiome including Porphyromonadaceae and Enterobacteriaceae. Decreasing bile acid concentration in the colon in cirrhosis is also associated with decreases in Clostridium cluster XIVa, which includes bile acid 7α-dehydroxylating bacteria which produce DCA. Rifaximin treatment appears to act by suppressing DCA production, reducing endotoxemia and harmful metabolites without significantly altering microbiome structure. Taken together, the bile acid pool size and composition appear to be a major regulator of microbiome structure, which in turn appears to be an important regulator of bile acid pool size and composition. The balance between this equilibrium is critical for human health and disease.
authors.affiliation: Department of Microbiology and Immunology; Virginia Commonwealth University; Richmond, VA USA; McGuire VA Medical Center; Richmond, VA USA.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Ridlon
authors.affiliation: Department of Microbiology and Immunology; Virginia Commonwealth University; Richmond, VA USA.
authors.forename: Joao Marcelo
authors.initials: JM
authors.lastname: Alves
authors.affiliation: Department of Microbiology and Immunology; Virginia Commonwealth University; Richmond, VA USA; McGuire VA Medical Center; Richmond, VA USA.
authors.forename: Phillip B
authors.initials: PB
authors.lastname: Hylemon
authors.affiliation: McGuire VA Medical Center; Richmond, VA USA; Division of Gastroenterology, Hepatology and Nutrition; Virginia Commonwealth University; Richmond, VA USA.
authors.forename: Jasmohan S
authors.initials: JS
authors.lastname: Bajaj
mesh_terms: D001647:Bile Acids and Salts / Q000032:analysis*; D005243:Feces / Q000737:chemistry*; D005260:Female; D006801:Humans; D007422:Intestines / Q000382:microbiology*; D008103:Liver Cirrhosis / Q000378:metabolism*; D008297:Male; D064307:Microbiota / Q000502:physiology*
chemical_list: D001647:Bile Acids and Salts
keywords: 7α-dehydroxylation; Clostridium cluster XIVa; MELD score; autochthonous; bile acids; cirrhosis; lachnospiraceae; rifaximin; ruminoccoccaceae