title: Tissue Microbiome Profiling Identifies an Enrichment of Specific Enteric Bacteria in Opisthorchis viverrini Associated Cholangiocarcinoma.
abstract: Cholangiocarcinoma (CCA) is the primary cancer of the bile duct system. The role of bile duct tissue microbiomes in CCA tumorigenesis is unestablished. To address this, sixty primary CCA tumors and matched normals, from both liver fluke (Opisthorchis viverrini) associated (OVa, n=28) and non-O. viverrini associated (non-OVa, n=32) cancers, were profiled using high-throughput 16S rRNA sequencing. A distinct, tissue-specific microbiome dominated by the bacterial families Dietziaceae, Pseudomonadaceae and Oxalobacteraceae was observed in bile duct tissues. Systemic perturbation of the microbiome was noted in tumor and paired normal samples (vs non-cancer normals) for several bacterial families with a significant increase in Stenotrophomonas species distinguishing tumors vs paired normals. Comparison of parasite associated (OVa) vs non-associated (non-OVa) groups identified enrichment for specific enteric bacteria (Bifidobacteriaceae, Enterobacteriaceae and Enterococcaceae). One of the enriched families, Bifidobacteriaceae, was found to be dominant in the O. viverrini microbiome, providing a mechanistic link to the parasite. Functional analysis and comparison of CCA microbiomes revealed higher potential for producing bile acids and ammonia in OVa tissues, linking the altered microbiota to carcinogenesis. These results define how the unique microbial communities resident in the bile duct, parasitic infections and the tissue microenvironment can influence each other, and contribute to cancer.
authors.affiliation: Genome Institute of Singapore, 138672, Singapore.
authors.forename: Kern Rei
authors.initials: KR
authors.lastname: Chng
authors.affiliation: Division of Medical Oncology, National Cancer Centre Singapore, 11 Hospital Drive, 169610, Singapore.
authors.forename: Sock Hoai
authors.initials: SH
authors.lastname: Chan
authors.affiliation: Genome Institute of Singapore, 138672, Singapore.
authors.forename: Amanda Hui Qi
authors.initials: AHQ
authors.lastname: Ng
authors.affiliation: Genome Institute of Singapore, 138672, Singapore.
authors.forename: Chenhao
authors.initials: C
authors.lastname: Li
authors.affiliation: Laboratory of Cancer Epigenome, National Cancer Centre Singapore, 11 Hospital Drive, 169610, Singapore.
authors.forename: Apinya
authors.initials: A
authors.lastname: Jusakul
authors.affiliation: Genome Institute of Singapore, 138672, Singapore.
authors.forename: Denis
authors.initials: D
authors.lastname: Bertrand
authors.affiliation: Genome Institute of Singapore, 138672, Singapore.
authors.forename: Andreas
authors.initials: A
authors.lastname: Wilm
authors.affiliation: Division of Medical Oncology, National Cancer Centre Singapore, 11 Hospital Drive, 169610, Singapore.
authors.forename: Su Pin
authors.initials: SP
authors.lastname: Choo
authors.affiliation: Department of Gastroenterology and Hepatology, Singapore General Hospital, Outram Road, 169608, Singapore.
authors.forename: Damien Meng Yew
authors.initials: DMY
authors.lastname: Tan
authors.affiliation: Department of Pathology, Singapore General Hospital, Outram Road, 169608, Singapore.
authors.forename: Kiat Hon
authors.initials: KH
authors.lastname: Lim
authors.affiliation: Department of Gastroenterology and Hepatology, Singapore General Hospital, Outram Road, 169608, Singapore.
authors.forename: Roy
authors.initials: R
authors.lastname: Soetinko
authors.affiliation: Laboratory of Cancer Epigenome, National Cancer Centre Singapore, 11 Hospital Drive, 169610, Singapore.
authors.forename: Choon Kiat
authors.initials: CK
authors.lastname: Ong
authors.affiliation: Edwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Dan G
authors.initials: DG
authors.lastname: Duda
authors.affiliation: Center of Digestive Diseases and Liver Transplantation, Fundeni Clinical Institute, Bucharest, Romania.
authors.forename: Simona
authors.initials: S
authors.lastname: Dima
authors.affiliation: Center of Digestive Diseases and Liver Transplantation, Fundeni Clinical Institute, Bucharest, Romania.
authors.forename: Irinel
authors.initials: I
authors.lastname: Popescu
authors.affiliation: Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Chaisiri
authors.initials: C
authors.lastname: Wongkham
authors.affiliation: Dept. of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Dept. of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Dept. of Gastroenterology and Hepatology, National University Health System, Singapore.
authors.forename: Khay Guan
authors.initials: KG
authors.lastname: Yeoh
authors.affiliation: Laboratory of Cancer Epigenome, National Cancer Centre Singapore, 11 Hospital Drive, 169610, Singapore; Cancer Science and Stem Cell Biology, Duke-NUS Graduate Medical School, 8 College Road, 169857, Singapore.
authors.forename: Bin Tean
authors.initials: BT
authors.lastname: Teh
authors.affiliation: Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Puangrat
authors.initials: P
authors.lastname: Yongvanit
authors.affiliation: Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Sopit
authors.initials: S
authors.lastname: Wongkham
authors.affiliation: Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Vajaraphongsa
authors.initials: V
authors.lastname: Bhudhisawasdi
authors.affiliation: Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Narong
authors.initials: N
authors.lastname: Khuntikeo
authors.affiliation: Genome Institute of Singapore, 138672, Singapore; Cancer Science and Stem Cell Biology, Duke-NUS Graduate Medical School, 8 College Road, 169857, Singapore.
authors.forename: Patrick
authors.initials: P
authors.lastname: Tan
authors.affiliation: Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. Electronic address: chawalit-pjk2011@hotmail.com.
authors.forename: Chawalit
authors.initials: C
authors.lastname: Pairojkul
authors.affiliation: Division of Medical Oncology, National Cancer Centre Singapore, 11 Hospital Drive, 169610, Singapore; Oncology Academic Clinical Program, Duke-NUS Graduate Medical School, 8 College Road, 169857, Singapore. Electronic address: Joanne.Ngeow.Yuen.Yie@nccs.com.sg.
authors.forename: Joanne
authors.initials: J
authors.lastname: Ngeow
authors.affiliation: Genome Institute of Singapore, 138672, Singapore. Electronic address: nagarajann@gis.a-star.edu.sg.
authors.forename: Niranjan
authors.initials: N
authors.lastname: Nagarajan
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001650:Bile Duct Neoplasms / Q000209:etiology*; D044822:Biodiversity; D002471:Cell Transformation, Neoplastic; D018281:Cholangiocarcinoma / Q000209:etiology*; D005260:Female; D000069196:Gastrointestinal Microbiome; D006801:Humans; D008297:Male; D054892:Metagenome; D056186:Metagenomics / Q000379:methods; D064307:Microbiota; D008875:Middle Aged; D009889:Opisthorchiasis / Q000150:complications* / Q000469:parasitology*; D009891:Opisthorchis; D009928:Organ Specificity; D012336:RNA, Ribosomal, 16S
chemical_list: D012336:RNA, Ribosomal, 16S
keywords: Cancer; Cholangiocarcinoma; Liver fluke; Microbiome