ABSTRACT: Background:Alcoholic hepatitis (AH) is associated with gut dysbiosis. Comparative gut microbial profiles of acute alcoholic pancreatitis (AAP) and acute biliary disease (ABD) are not demonstrated. We aimed to compare gut microbiota of AH, AAP, and ABD patients with each other and with their respective healthy controls (HCs). Methods:From December 2016 to September 2017, consecutive patients with AH, AAP, and ABD (acute cholecystitis, acute biliary pancreatitis, and choledocholithiasis with cholangitis) were included in the study. Qualitative and functional stool microbiota comparative analysis was performed between groups, with AH as the reference comparator. Results:Of 3564, 882, and 224 patients with liver disease, pancreatic disease, and biliary disease, respectively, after exclusion, 29 patients with AH and 7 patients each with AAP and ABD and their corresponding HCs were included in the study analysis. The alpha diversity between patients with AH and AAP was found to be significantly different. Significant relative abundance (RA) of Acinetobacter and Moraxella was noted among patients with AAP. Enterobacter, Atopobium, Synergistia, and Devosia were significantly higher in patients with ABD compared to patients with AH, in whom Faecalibacterium and Megamonas were higher. Functional pathways associated with carbohydrate metabolism, phenylpropanoid biosynthesis, and ethylbenzene degradation were significantly higher in AAP when compared to AH. Fatty acid and inositol phosphate metabolism and dioxin degradation were significantly upregulated in patients with ABD while lipid and fatty acid biosynthetic pathways and pathways associated with immune processes were upregulated in patients with AH. Conclusions:Differential gut dysbiosis is evident in both patients with AH, AAP, and ABD and also in comparison to HCs. The differential microbiota among patients with AH and AAP maybe important in promotion and progression of liver or pancreatic disease among alcohol users and may be a potential therapeutic target, which needs to be confirmed in larger multicenter studies.