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      • Bile Acids and Intestinal Dysbiosis in Alcoholic Hepatitis

        ( Dragos Ciocan ),( Cosmin Sebastian Voican ),( Laura Wrzosek ),( Cindy Hugot ),( Gabriel Perlemuter ),( Anne-marie Cassard ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

        Aims: Alcoholic liver disease is associated with dysbiosis, impaired gut barrier and inflammation. Intestinal microbiota (IM) plays an important role in bile acids (BA) homeostasis and impact the gut barrier and promotes inflammation. The aim of our study was to study the structure of the IM and its function in BA homeostasis in alcoholic patients according to the severity of alcoholic liver disease. Methods: We included in a prospective study 4 groups of active alcoholic patients (N=97): two non-cirrhotic (nc) without or with alcoholic hepatitis (AH) (noAHnc, N=54 or AHnc N=14, respectively) and two cirrhotic groups without or with AH (noAHc, N=16 or sAHc, N=13, respectively). Serum and fecal BA profiles, as well as IM composition, using high-throughput 16s sequencing, were assessed. Results: In sAHc patients compared to noAHc patients, there was an increase in serum total BA, primary BA (total CA and total CDCA), conjugated BA and tauro-glycoconjugated ratio and a decrease in the UDCA/total BA and secondary/primary ratio. In feces, there was a decrease in total BA and an increase in secondary BA (total LCA and DCA). These 2 groups had a different IM structure. At the phyla level, there was an increase in Actinobacteria and a decrease in Bacteroidetes; 7 genera were increased and 4 were decreased. Moreover, in sAHc patients compared to noAHc patients, there was an increase in 4 and a decrease in 11 metabolic pathways (eg increase in glutathion and nucleotid metabolism, phosphotransferase system). In AHnc patients as compared to noAHnc, there was an increase in serum total conjugated BA. The IM of AHnc patients was characterized by an increase in Wolbachia and Dorea as compared to noAHnc. Conclusions: Disruption of BA homeostasis associated with alcoholic hepatitis is correlated to a specific IM signature that may lead to liver disease progression.

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