Pancreatic cancers have high mortality and rising incidence rates which may be related to unhealthy western-type dietary and lifestyle patterns as well as increasing body weights and obesity rates. Recent data also suggest a role for the gut microbiome in the development of pancreatic cancer. Here, we review the experimental and observational evidence for the roles of the oral, gut and intratumoural microbiomes, impaired gut barrier function and exposure to inflammatory compounds as well as metabolic dysfunction as contributors to pancreatic disease with a focus on pancreatic ductal adenocarcinoma (PDAC) initiation and progression. We also highlight some emerging gut microbiome editing techniques currently being investigated in the context of pancreatic disease. Notably, while the gut microbiome is significantly altered in PDAC and its precursor diseases, its utility as a diagnostic and prognostic tool is hindered by a lack of reproducibility and the potential for reverse causality in case-control cohorts. Future research should emphasise longitudinal and mechanistic studies as well as integrating lifestyle exposure and multi-omics data to unravel complex host-microbiome interactions. This will allow for deeper aetiologic and mechanistic insights that can inform treatments and guide public health recommendations.

Department of Biology University of Pisa Pisa Italy

Department of Pathophysiology Faculty of Medicine University of Sarajevo Sarajevo Bosnia and Herzegovina

Laboratory of Pharmacogenomics Biomedical Center Faculty of Medicine in Pilsen Charles University Pilsen Czech Republic; Toxicogenomics Unit National Institute of Public Health Prague Czech Republic

Molecular Epidemiology of Cancer Group UCD Conway Institute School of Biomedical and Biomolecular Sciences University College Dublin Dublin Ireland

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