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This is the first study to investigate both bile and stool microbiota profiles in PSC and CCA, mostly perihilar CCA. Samples with less than 2000 reads were excluded from the compositional analysis to reduce false associations. We adjusted for demographic and clinical factors influencing the biliary and stool microbiota in PSC and CCA patients. Bile and stool have different profiles of microbiota, although the bile and stool microbiome from the same subject showed more similarity than those from different subjects. Increased species richness and abundance of Fusobacteria in bile was correlated with the duration of PSC and characterized the bile of CCA patients. The unique microbial signature in the bile of patients with CCA raises the possibility of a role for microbiota-driven inflammation in the pathogenesis of perihilar CCA.

Background: Primary sclerosing cholangitis (PSC) is a major risk factor for cholangiocarcinoma (CCA). We investigated biliary and fecal microbiota to determine whether specific microbes in the bile or stool are associated with PSC or CCA. Methods: Bile was obtained from 32 patients with PSC, 23 with CCA with PSC, 26 with CCA without PSC, and 17 controls. Over 90% of bile samples were from patients with perihilar CCA. Stool was obtained from 31 patients with PSC (11 were matched to bile), 16 with CCA with PSC (10 matched to bile), and 11 with CCA without PSC (6 matched to bile). Microbiota composition was assessed using 16SrRNA-marker-based sequencing and was compared between groups. Results: Bile has a unique microbiota distinguished from …