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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.

      • Different Intestinal Microbiota Profile in Alcoholic Pancreatitis as Compared to Alcoholic Hepatitis

        ( Dragos Ciocan ),( Vinciane Rebours ),( Anne-marie Cassard ),( Laura Wrzosek ),( Cosmin Sebastian Voican ),( Virginie Puchois ),( Philippe Levy ),( Gabriel Perlemuter ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

        Aims: Chronic excessive alcohol consumption may cause alcoholic liver disease (ALD) or alcoholic pancreatitis (AP) in only a subset of patients. We have shown that individual susceptibility to ALD is substantially driven by intestinal microbiota (IM). However, factors related to tissue predilection (liver or pancreas) to alcohol toxicity are unknown. We aimed to characterize the IM profile in alcoholic patients according to the presence and the nature of the complication ie severe alcoholic hepatitis (sAH) or AP. Methods: Eighty-two alcoholic patients were included into 3 groups according to their complications: AP (N=24), sAH (N=13) and no complication despite a similar amount of alcohol consumption (alcoholic controls, N=45). IM was analyzed using high-throughput sequencing of the 16S Ribosomal RNA (16S RNA) gene. Results: Patients with AP had a reduced bacterial diversity (p=0.001) and a different global microbial composition as compared to alcoholic controls (p=0.001). 17 taxa at the genus level were different between the 2 groups; among them, 8 were increased in AP (Klebsiella, Enterococcus, Aquabacterium and Sphingomonas). When compared to sAH there was no difference in bacterial diversity between the 2 groups. However, 16 taxa were increased in sAH and 10 in AP. After adjusting for confounding factors (age, sex, BMI, alcohol intake, diabetes and proton-pump inhibitors) there was a marked increase in Haemophilus in sAH patients. Conclusions: Patients with AP have a specific dysbiosis as compared to alcoholic controls. Specific microbiome signatures are associated with AP and sAH.

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