Enrichment of oral microbiota in early cystic precursors to invasive pancreatic cancer
Open accessAbstract
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.
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Various disease states are associated with the oral microbiome, including caries, periodontal disease, oral, esophageal, pancreatic, and colorectal cancers, cardiovascular disease, and inflammatory bowel disease.
“This is demonstrated by the association of various disease states with the oral microbiome, including not only caries and periodontal disease but also oral, esophageal, pancreatic, and colorectal cancers, cardiovascular disease, and inflammatory bowel disease.147, 148, 149, 150, 151, 152, 153”
From The oral microbiome: Role of key organisms and complex networks in oral health and disease (2021) · cites this paper as [151]
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- Authors
- Gaiser, R. A., Halimi, A., Alkharaan, H., Lu, L., Davanian, H., Healy, K., Hugerth, L. W., Ateeb, Z., Valente, R., Fernández Moro, C., Del Chiaro, M., & Sällberg Chen, M.
- Affiliations
- Karolinska Institutet (SE)
- Karolinska University Hospital (SE)
- Tongji University (CN)
- Science for Life Laboratory (SE)
- Division of Pathology, Department of Laboratory Medicine (LABMED), Karolinska Institutet, Huddinge, Sweden
- Pancreatic Surgery Unit, Division of Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Universitetsjukhuset i Huddinge, Huddinge, Sweden
- Department of Dental Medicine, Karolinska Institutet, Huddinge, Sweden
- ORCID
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2019-03-14
- Volume
- 68
- Issue
- 12
- Pages
- 2186-2194
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- PMC
- PMC6872446
- OpenAlex
- W2921125196
- Cited by
- 227
- References
- 48
- Citations by year
- 2026: 15 · 2025: 31 · 2024: 29 · 2023: 28 · 2022: 42 · 2021: 47 · 2020: 28 · 2019: 6
- FWCI
- 12.85
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Gut (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Ruth och Richard Julins funds
- Karolinska Institutet funds
- ALF
- Cancerfonden
- SOF Strategic Odontological Research
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Keywords
- intraductal papillary mucinous neoplasm, pancreatic cysts, oral microbiota, Fusobacterium nucleatum, Granulicatella adiacens, IL-1β, high-grade dysplasia, cyst fluid, bacterial DNA, endoscopy, proton pump inhibitors, pancreatic cancer precursors
- MeSH terms
- Adult, Aged, Aged, 80 and over, Biopsy, DNA, Bacterial, Female, Humans, Male, Middle Aged, Mouth, Neoplasm Invasiveness, Pancreatectomy, Pancreatic Ducts, Pancreatic Neoplasms, Retrospective Studies, Carcinoma, Pancreatic Ductal, Microbiota
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