Bile acid homeostasis and intestinal dysbiosis in alcoholic hepatitis

• DOI: 10.1111/apt.14949
• Publication Date: 2018-08-24T08:26:38Z
• Authors: Dragos Ciocan; Cosmin Sebastian ...; Laura Wrzosek; Cindy Hugot; Dominique Rainteau; Lydie Humbert; Anne‐Marie Cassard; Gabriel Perlemuter
• Keywords: Adult; Diarrhea; Male; 0301 basic medicine; [SDV]Life Sciences [q-bio]; 610; UDCA; 16S sequencing; Bile Acids and Salts; Feces; 03 medical and health sciences; biotin; Liver Cirrhosis, Alcoholic; microbiota; Homeostasis; Humans; Prospective Studies; glutathione; Aged; Bacteroidetes; Hepatitis, Alcoholic; 600; [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology; Middle Aged; Gastrointestinal Microbiome; 3. Good health; Actinobacteria; Dysbiosis; Female; France

SummaryBackgroundIntestinal microbiota plays an important role in bile acid homeostasis.AimTo study the structure of the intestinal microbiota and its function in bile acid homeostasis in alcoholic patients based on the severity of alcoholic liver disease.MethodsIn this prospective study, we included four groups of active alcoholic patients (N = 108): two noncirrhotic, with (noCir_AH, n = 13) or without alcoholic hepatitis (noCir_noAH, n = 61), and two cirrhotic, with (Cir_sAH, n = 17) or without severe alcoholic hepatitis (Cir_noAH, n = 17). Plasma and faecal bile acid profiles and intestinal microbiota composition were assessed.ResultsPlasma levels of total bile acids (84.6 vs 6.8 μmol/L, P < 0.001) and total ursodeoxycholic acid (1.3 vs 0.3 μmol/L, P = 0.03) were higher in cirrhosis with severe alcoholic hepatitis (Cir_sAH) than Cir_noAH, whereas total faecal (2.4 vs 11.3, P = 0.01) and secondary bile acids (0.7 vs 10.7, P < 0.01) levels were lower. Cir_sAH patients had a different microbiota than Cir_noAH patients: at the phyla level, the abundance of Actinobacteria (9 vs 1%, P = 0.01) was higher and that of Bacteroidetes was lower (25 vs 40%, P = 0.04). Moreover, the microbiota of Cir_sAH patients showed changes in the abundance of genes involved in 15 metabolic pathways, including upregulation of glutathione metabolism, and downregulation of biotin metabolism.ConclusionsPatients with Cir_sAH show specific changes of the bile acid pool with a shift towards more hydrophobic and toxic species that may be responsible for the specific microbiota changes. Conversely, the microbiota may also alter the bile acid pool by transforming primary to secondary bile acids, leading to a vicious cycle.