Enrichment of oral microbiota in early cystic precursors to invasive pancreatic cancer
Authors: Marco Del Chiaro
Rogier Aäron Gaiser
Haleh Davanian
Katie Healy
Hassan Alkharaan
Carlos Fernández Moro
Asif Halimi
Liyan Lu
Roberto Valente
Luisa W Hugerth
Zeeshan Ateeb
Margaret Sällberg Chen
Journal: Gut (2019)
Discipline: CLINICAL MEDICINE
Keywords: bacterial translocation; endoscopic procedure; inflammation; pancreatic surgery; pancreatic tumours.
Affiliations: Department of Dental Medicine, Karolinska Institutet, Huddinge, Sweden., Pancreatic Surgery Unit, Division of Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Universitetsjukhuset i Huddinge, Huddinge, Sweden., Tenth People's Hospital, Tongji University, Shanghai, China., Center for Translational Microbiome Research, CTMR, Department of Microbiology, Tumour and Cell Biology (MTC), Karolinska Institutet, Science for Life Laboratory, Huddinge, Sweden., Division of Pathology, Department of Laboratory Medicine (LABMED), Karolinska Institutet, Huddinge, Sweden., Department of Clinical Pathology/Cytology, Karolinska University Hospital, Huddinge, Sweden., Division of Surgical Oncology, Department of Surgery, University of Colorado at Denver-Anschutz Medical Campus, Aurora, Colorado, USA.

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. 

Retracted: No

PubPeer comments:
 The authors explore a new biome here, and seem to have handled all procedures correctly with including a negative control. Set, some samples show high amount of Methylobacterium, which is a common contaminant, and a very uncommon human associated bacterium. Many of the other organisms in this investigation are also possible contaminants, due to the fact that they are common human skin mouth organisms, so their actual presence could be considered likely. While the authors investigated the DNA load of the samples, no negative control was employed, so it also cannot be excluded that these samples were contaminated during sampling. ,