Dragos Ciocan1, Cosmin Sebastian Voican1,2, Laura Wrzosek1,2, Cindy Hugot1, Dominique Rainteau3,4,5,6, Lydie Humbert3,4,5, Anne-Marie Cassard1, Gabriel Perlemuter1,2. 1. Inflammation Chimiokines et Immunopathologie, DHU Hepatinov, Faculté de Médecine-Université Paris-Sud/Université Paris-Saclay, INSERM, UMR-S 996, Clamart, France. 2. AP-HP, Hepatogastroenterology and Nutrition, Hôpital Antoine-Béclère, Clamart, France. 3. UPMC Université Paris 6, Sorbonne Universités, Paris, France. 4. Inflammation-Immunopathology-Biotherapy Department (DHU i2B), INSERM-ERL 1157, Paris, France. 5. UMR 7203, Laboratoire des Biomolécules, UPMC/CNRS/ENS, Paris, France. 6. Département PM2 Plateforme de Métabolomique, APHP, Hôpital Saint Antoine, Peptidomique et dosage de Médicaments, Paris, France.
Abstract
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_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. 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_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. 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.
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 alcoholicpatients based on the severity of alcoholic liver disease. METHODS: In this prospective study, we included four groups of active alcoholicpatients (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. 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_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_sAHpatients 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_sAHpatients 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.
Authors: Bei Gao; Yi Duan; Sonja Lang; Dinesh Barupal; Tsung-Chin Wu; Luis Valdiviez; Bryan Roberts; Ying Yng Choy; Tong Shen; Gregory Byram; Ying Zhang; Sili Fan; Benjamin Wancewicz; Yan Shao; Kevin Vervier; Yanhan Wang; Rongrong Zhou; Lu Jiang; Shilpa Nath; Rohit Loomba; Juan G Abraldes; Ramon Bataller; Xin M Tu; Peter Stärkel; Trevor D Lawley; Oliver Fiehn; Bernd Schnabl Journal: Hepatol Commun Date: 2020-06-19