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. Enders; Sumera H. Ilyas; Gregory J. Gores; Mark D. Topazian; Purna C. Kashyap; Lewis R. Roberts

doi:10.3390/cancers14092120

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 journal › Article › peer-review

Abstract

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 language	English (US)
Article number	2120
Journal	Cancers
Volume	14
Issue number	9
DOIs	https://doi.org/10.3390/cancers14092120
State	Published - May 1 2022

Keywords

bile microbiome
cholangiocarcinoma
primary sclerosing cholangitis

ASJC Scopus subject areas

Oncology
Cancer Research

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10.3390/cancers14092120

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Miyabe, K., Chandrasekhara, V., Wongjarupong, N., Chen, J., Yang, L., Johnson, S., Chia, N., Walther-Antonio, M., Yao, J. Z., Harrington, S. C., Nordyke, C. K., Eaton, J. E., Gossard, A. A., Oli, S., Ali, H. A., Lavu, S., Giama, N. H., Hassan, F. A., Ali, H. M., ... Roberts, L. R. (2022). Potential Role of Inflammation-Promoting Biliary Microbiome in Primary Sclerosing Cholangitis and Cholangiocarcinoma. Cancers, 14(9), [2120]. https://doi.org/10.3390/cancers14092120

Miyabe, K, Chandrasekhara, V, Wongjarupong, N, Chen, J, Yang, L, Johnson, S, Chia, N , Walther-Antonio, M, Yao, JZ, Harrington, SC, Nordyke, CK, Eaton, JE, Gossard, AA, Oli, S, Ali, HA, Lavu, S, Giama, NH, Hassan, FA, Ali, HM, Enders, FT , Ilyas, SH , Gores, GJ, Topazian, MD, Kashyap, PC & Roberts, LR 2022, 'Potential Role of Inflammation-Promoting Biliary Microbiome in Primary Sclerosing Cholangitis and Cholangiocarcinoma', Cancers, vol. 14, no. 9, 2120. https://doi.org/10.3390/cancers14092120

@article{b7871502a56b427abce8a4d2f2b752f0,

title = "Potential Role of Inflammation-Promoting Biliary Microbiome in Primary Sclerosing Cholangitis and Cholangiocarcinoma",

abstract = "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.",

keywords = "bile microbiome, cholangiocarcinoma, primary sclerosing cholangitis",

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

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: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2022",

month = may,

day = "1",

doi = "10.3390/cancers14092120",

language = "English (US)",

volume = "14",

journal = "Cancers",

issn = "2072-6694",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "9",

}

TY - JOUR

T1 - Potential Role of Inflammation-Promoting Biliary Microbiome in Primary Sclerosing Cholangitis and Cholangiocarcinoma

AU - Miyabe, Katsuyuki

AU - Chandrasekhara, Vinay

AU - Wongjarupong, Nicha

AU - Chen, Jun

AU - Yang, Lu

AU - Johnson, Stephen

AU - Chia, Nicholas

AU - Walther-Antonio, Marina

AU - Yao, Janet Z.

AU - Harrington, Sean C.

AU - Nordyke, Cynthia K.

AU - Eaton, John E.

AU - Gossard, Andrea A.

AU - Oli, Sharad

AU - Ali, Hamdi A.

AU - Lavu, Sravanthi

AU - Giama, Nasra H.

AU - Hassan, Fatima A.

AU - Ali, Hawa M.

AU - Enders, Felicity T.

AU - Ilyas, Sumera H.

AU - Gores, Gregory J.

AU - Topazian, Mark D.

AU - Kashyap, Purna C.

AU - Roberts, Lewis R.

N1 - 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.

PY - 2022/5/1

Y1 - 2022/5/1

N2 - 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.

AB - 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.

KW - bile microbiome

KW - cholangiocarcinoma

KW - primary sclerosing cholangitis

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UR - http://www.scopus.com/inward/citedby.url?scp=85128748172&partnerID=8YFLogxK

U2 - 10.3390/cancers14092120

DO - 10.3390/cancers14092120

M3 - Article

AN - SCOPUS:85128748172

SN - 2072-6694

VL - 14

JO - Cancers

JF - Cancers

IS - 9

M1 - 2120

ER -

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

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