Bile acid homeostasis and intestinal dysbiosis in alcoholic hepatitis

Dragos Ciocan (1) , Cosmin Sebastian Voican (2, 1) , Laura Wrzosek (1, 2) , Cindy Hugot (1) , Dominique Rainteau (3, 4, 5, 6) , Lydie Humbert (3, 4, 5) , Anne-Marie Cassard (1) , Gabriel Perlemuter (7, 1)

1 UP11 UFR Médecine - Université Paris-Sud - Paris 11 - Faculté de médecine
2 Hôpital Antoine Béclère
3 SU - Sorbonne Université
4 CHU Pitié-Salpêtrière [AP-HP]
5 LBM UMR 7203 - Laboratoire des biomolécules
6 CHU Saint-Antoine [AP-HP]
7 AP-HP - Hôpital Antoine Béclère [Clamart]

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.

Mots clés: biotin; glutathione; microbiota; UDCA; 16S sequencing; Actinobacteria; Bacteroidetes

Domaines: Hépatologie et Gastroentérologie

Dragos Ciocan, Cosmin Sebastian Voican, Laura Wrzosek, Cindy Hugot, Dominique Rainteau, et al.. Bile acid homeostasis and intestinal dysbiosis in alcoholic hepatitis. Alimentary Pharmacology and Therapeutics, 2018, 48 (9), pp.961-974. ⟨10.1111/apt.14949⟩. ⟨hal-02022884⟩