IDDF2020-ABS-0025 The role of gut microbiota in clinical complications and treatment response in alcoholic hepatitis – a CIRCOS®, linear discriminant analysis effect size biomarker and CONET® co-occurrence network analysis. (18th November 2020)

• Record Type: Journal Article
• Authors: Philips, Cyriac; Ganesan, Karthik; Ranade, Shatakshi; Chopra, Varun; Patil, Kunal; Shende, Sonie; Phadke, Nikhil; Augustine, Philip
• Is Part Of: Gut. Volume 69(2020)Supplement 2
• Page Start: A23
• Page End: A24
• Publication Date: 2020-11-18
• Subjects: Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gutjnl-2020-IDDF.34
• Languages: English
• ISSNs: 0017-5749

Abstract

Abstract : Background: In severe alcoholic hepatitis(SAH), we aimed to characterize significant bacterial communities associated with clinical events(CE) and define bacterial relationships associated with specific CE and outcomes at baseline and on corticosteroids. Methods: 16-s rRNA sequencing on stool samples(n=38) collected at admission and at last follow-up within 90-days was (N=26, 12 on corticosteroids). Visual-characterization was performed on QIIME data using CIRCOS™, linear-discriminant-analysis-effect-size (LEfSe) method was used to identify significant bacterial communities and their functional metabolites. Conet/Cytoscape® utilized to identify significant co-occurrence with respect to clinical events. Results: All were males with mean age 47.3±9.1 years, median discriminant function(DF) 64, Child-Pugh(CTP)12 and model for end-stage liver disease(MELD)25.5. At admission, 27%, 42%, and 58% had acute kidney injury (AKI), hepatic encephalopathy (HE) and infections respectively; 38.5% died at 90-days follow-up. Specific bacteria were found to be associated with HE [Bifidobacteriaceae, Coriobacteriaceae], sepsis [Veillonellaceae, Prevotellaceae], CTP>10 [Bifidobacteriaceae, Synergistaceae], MELD>25 [Dehalobacteriaceae, Turicibacteraceae] and death [Enterobacteriaceae, Peptococcaceae]. Significantly higher relative abundance(RA) of Lachnobacterium, Catenibacterium associated with HE at-admission while orally-represented bacteria were associated with infections at admission. Propionibacterium, Fusobacteria were associated with DF≥65 while Eubacterium, Capnocytophaga were associated with CTP. Enhydrobacter and Pediococcus were preferentially abundant post-steroid-therapy. Aerococcus was associated with post-treatment death. Prevotella was associated with survival post steroid. Upregulation of phenylpropanoid-biosynthesis(innate-immunity) in those without follow-up infections and glycerophospholipid-metabolism(cellular-integrity) in those who died were significant. Co-occurrence between Christensenella, Prevotella and mutual-exclusion between Megamonas, Citrobacter was associated with HE at admission. Mutual-exclusion between Coprococcus eutactus, Catenibacterium and Megamonas was associated with infections at admission while Enterococcus cecorum, Acinetobacter schindleri, Mitsuokella were associated with AKI at admission (figure 1 ). Conclusions: Specific gut-microbiota, their interactions and metabolites are associated with complications of SAH as well as outcomes with steroid-therapy. Advanced metagenomics-based precision-medicine as add-on treatments may be a novel therapeutic area for improving disease outcomes.