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Original article
Enrichment of oral microbiota in early cystic precursors to invasive pancreatic cancer
  1. Rogier Aäron Gaiser1,
  2. Asif Halimi2,
  3. Hassan Alkharaan1,
  4. Liyan Lu1,3,
  5. Haleh Davanian1,
  6. Katie Healy1,
  7. Luisa W Hugerth4,
  8. Zeeshan Ateeb2,
  9. Roberto Valente2,
  10. Carlos Fernández Moro5,6,
  11. Marco Del Chiaro2,7,
  12. Margaret Sällberg Chen1,3
  1. 1 Department of Dental Medicine, Karolinska Institutet, Huddinge, Sweden
  2. 2 Pancreatic Surgery Unit, Division of Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Universitetsjukhuset i Huddinge, Huddinge, Sweden
  3. 3 Tenth People’s Hospital, Tongji University, Shanghai, China
  4. 4 Center for Translational Microbiome Research, CTMR, Department of Microbiology, Tumour and Cell Biology (MTC), Karolinska Institutet, Science for Life Laboratory, Huddinge, Sweden
  5. 5 Division of Pathology, Department of Laboratory Medicine (LABMED), Karolinska Institutet, Huddinge, Sweden
  6. 6 Department of Clinical Pathology/Cytology, Karolinska University Hospital, Huddinge, Sweden
  7. 7 Division of Surgical Oncology, Department of Surgery, University of Colorado at Denver—Anschutz Medical Campus, Aurora, Colorado, USA
  1. Correspondence to Dr Margaret Sällberg Chen, Department of Dental Medicine, Karolinska Institutet, Huddinge 14141, Sweden; margaret.chen{at}ki.se

Abstract

Objectives Intraductal papillary mucinous neoplasms (IPMNs) are pancreatic cysts that can progress to invasive pancreatic cancer. Associations between oncogenesis and oral microbiome alterations have been reported. This study aims to investigate a potential intracystic pancreatic microbiome in a pancreatic cystic neoplasm (PCN) surgery patient cohort.

Design Paired cyst fluid and plasma were collected at pancreatic surgery from patients with suspected PCN (n=105). Quantitative and qualitative assessment of bacterial DNA by qPCR, PacBio sequencing (n=35), and interleukin (IL)-1β quantification was performed. The data were correlated to diagnosis, lesion severity and clinical and laboratory profile, including proton-pump inhibitor (PPI) usage and history of invasive endoscopy procedures.

Results Intracystic bacterial 16S DNA copy number and IL-1β protein quantity were significantly higher in IPMN with high-grade dysplasia and IPMN with cancer compared with non-IPMN PCNs. Despite high interpersonal variation of intracystic microbiota composition, bacterial network and linear discriminant analysis effect size analyses demonstrated co-occurrence and enrichment of oral bacterial taxa including Fusobacterium nucleatum and Granulicatella adiacens in cyst fluid from IPMN with high-grade dysplasia. The elevated intracystic bacterial DNA is associated with, but not limited to, prior exposure to invasive endoscopic procedures, and is independent from use of PPI and antibiotics.

Conclusions Collectively, these findings warrant further investigation into the role of oral bacteria in cystic precursors to pancreatic cancer and have added values on the aetiopathology as well as the management of pancreatic cysts.

  • pancreatic tumours
  • bacterial translocation
  • inflammation
  • pancreatic surgery
  • endoscopic procedure

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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Footnotes

  • Contributors Study design: MDC, MSC, RV, RAG. Sample collection and processing: MDC, AH, HD, RAG, KH, ZA, CFM. Clinical data collection and interpretation: ZA, RV, AH, CFM, RAG. Laboratory work: RAG, HD, HA, KH, LL. Bioinformatic analysis and statistics: LWH, RAG. Manuscript preparation: RAG, MSC, RV, KH. Approval of final draft submission: RAG, AH, HA, LL, HD, KH, LWH, ZA, RV, CFM, MDC, MSC.

  • Funding This work was supported by the Swedish Cancer Society (CAN2016/731 to MSC) (CAN 2014/634, CAN 2015/621, CAN 2017/409, CAN 2017/419 to MDC). Ruth och Richard Julins funds, Karolinska Institutet funds, KI KID funding, and SOF KI/SLL för odontologisk forskning (to MSC). The Stockholm County Council (ALF SLL20150113) (to MDC).

  • Competing interests None declared.

  • Ethics approval This study follows the Helsinki convention and good clinical practice and was approved by the Regional Ethics Committee at Stockholm (Dnr. 2015/1580-31/1).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Patient consent for publication Not required.

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