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Bile acid homeostasis and intestinal dysbiosis in alcoholic hepatitis
Author(s) -
Ciocan Dragos,
Voican Cosmin Sebastian,
Wrzosek Laura,
Hugot Cindy,
Rainteau Dominique,
Humbert Lydie,
Cassard AnneMarie,
Perlemuter Gabriel
Publication year - 2018
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/apt.14949
Subject(s) - bile acid , alcoholic hepatitis , medicine , gastroenterology , alcoholic liver disease , ursodeoxycholic acid , chenodeoxycholic acid , dysbiosis , gut flora , cirrhosis , immunology , disease
Summary Background Intestinal microbiota plays an important role in bile acid homeostasis. Aim To 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. Methods In 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_no AH , n = 61), and two cirrhotic, with (Cir_ sAH , n = 17) or without severe alcoholic hepatitis (Cir_no AH , n = 17). Plasma and faecal bile acid profiles and intestinal microbiota composition were assessed. Results Plasma 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_no AH , 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_no AH 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. Conclusions Patients 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.