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. 2021 Jan-Dec;13(1):1983101.
doi: 10.1080/19490976.2021.1983101.

Isolation of pancreatic microbiota from cystic precursors of pancreatic cancer with intracellular growth and DNA damaging properties

Asif Halimi  1   2 , Giorgio Gabarrini  3 , Michał Jacek Sobkowiak  3 , Zeeshan Ateeb  1 , Haleh Davanian  3 , Rogier Aäron Gaiser  3 , Urban Arnelo  1   2 , Roberto Valente  1   2 , Alicia Y W Wong  4   5 , Carlos Fernández Moro  6   7 , Marco Del Chiaro  8 , Volkan Özenci  4   5 , Margaret Sällberg Chen  3
Affiliations

Isolation of pancreatic microbiota from cystic precursors of pancreatic cancer with intracellular growth and DNA damaging properties

Asif Halimi et al. Gut Microbes. 2021 Jan-Dec.

Abstract

Emerging research suggests gut microbiome may play a role in pancreatic cancer initiation and progression, but cultivation of the cancer microbiome remains challenging. This pilot study aims to investigate the possibility to cultivate pancreatic microbiome from pancreatic cystic lesions associated with invasive cancer. Intra-operatively acquired pancreatic cyst fluid samples showed culture-positivity mainly in the intraductal papillary mucinous neoplasm (IPMN) group of lesions. MALDI-TOF MS profiling analysis shows Gammaproteobacteria and Bacilli dominate among individual bacteria isolates. Among cultivated bacteria, Gammaproteobacteria, particularly Klebsiella pneumoniae, but also Granulicatella adiacens and Enterococcus faecalis, demonstrate consistent pathogenic properties in pancreatic cell lines tested in ex vivo co-culture models. Pathogenic properties include intracellular survival capability, cell death induction, or causing DNA double-strand breaks in the surviving cells resembling genotoxic effects. This study provides new insights into the role of the pancreatic microbiota in the intriguing link between pancreatic cystic lesions and cancer.

Keywords: IPMN; Pancreatic cancer; microbiota; pancreatic cystic neoplasm.

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Conflict of interest statement

MDC has been awarded an industry grant (Haemonetics, Inc) to conduct a multi-center study to evaluate the prognostic implications of TEG in pancreas cancer, and is co-PI of a sponsored Boston Scientific study on the use of intra-operative pancreatoscopy in IPMN’s patients not included in this study. No potential conflict of interest was reported by other authors.

Figures

Figure 1.
Figure 1.
DNA damage induced by infection with bacterial isolates in healthy (hTERT-HPNE), early (Capan-2) and late differentiation stage cancer (AsPC-1) pancreatic cell lines. (a-c) Representative stain of histone H2A.X phosphorylation in response to the isolate panel in hTERT-HPNE (a), Capan-2 (b) and AsPC-1 (c) cell lines. Numbers denote percentage positive events. (d) Histone H2A.X phosphorylation in response to the isolate panel in hTERT-HPNE, Capan-2 and AsPC-1 cell lines (n = 3). (e) Representative stain of histone H2A.X phosphorylation in response to E. cloacae (C2) with or without penicillin/streptomycin presence in the AsPC-1 cell line. (f) Inhibition of histone H2A.X phosphorylation in response to E. cloacae (C2/L2) in the presence of penicillin/streptomycin in the AsPC-1 cell line (n = 3). Statistical significance was determined using unpaired t-test with Welch’s correction. Statistical data for pH2A.X relative change (D) was computed on raw geometric MFI values (*p < .05, **p < .01, ***p < .001)
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