Potential Role of Inflammation-Promoting Biliary Microbiome in Primary Sclerosing Cholangitis and Cholangiocarcinoma

Katsuyuki Miyabe, Vinay Chandrasekhara, Nicha Wongjarupong, Jun Chen, Lu Yang, Stephen Johnson, Nicholas Chia, Marina Walther-Antonio, Janet Z. Yao, Sean C. Harrington, Cynthia K. Nordyke, John E. Eaton, Andrea A. Gossard, Sharad Oli, Hamdi A. Ali, Sravanthi Lavu, Nasra H. Giama, Fatima A. Hassan, Hawa M. Ali, Felicity T. EndersSumera H. Ilyas, Gregory J. Gores, Mark D. Topazian, Purna C. Kashyap, Lewis R. Roberts

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Background: Primary sclerosing cholangitis (PSC) is a major risk factor for cholangiocar-cinoma (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 negative DNA controls and stool. Increased species richness and abundance of Fusobacteria correlated with duration of PSC and characterized the biliary microbiota in CCA. Stool microbiota composition showed no significant differences between groups. Conclusions: We identified a unique microbial signature in the bile of patients with increased duration of PSC or with CCA, suggesting a role for microbiota-driven inflammation in the pathogenesis and or progression to perihilar CCA. Further studies are needed to test this hypothesis.

Original languageEnglish (US)
Article number2120
Issue number9
StatePublished - May 1 2022

Bibliographical note

Funding Information:
Funding: This work was supported by a 2016 ACG Clinical Research Award (ACG-CR-012-2016), the Mayo Clinic Center for Clinical and Translational Science (UL1TR002377), the Mayo Clinic Specialized Program of Research Excellence in Hepatobiliary Cancer (SPORE; P50CA210964), the Clinical Core of the Mayo Clinic Center for Cell Signaling in Gastroenterology (C-SIG; P30DK084567), and the Mayo Clinic Center for Individualized Medicine.

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.


  • bile microbiome
  • cholangiocarcinoma
  • primary sclerosing cholangitis


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