Multifaceted effects of the microbiome in pancreatic cancer: from association to modulation

Investigations into the microbiome in human diseases have exponentially increased over the past several decades, and the microbiome has been associated with nearly every malignancy, with research moving beyond associative studies to investigations into the microbiome as a causative factor in carcinogenesis. Pancreatic ductal adenocarcinoma (PDAC), the most common malignancy of the pancreas, is a major cause of worldwide cancer mortality owing to the lack of screening methods, late stage at diagnosis and poor response to currently available treatments. Microbiome-pancreatic cancer research has advanced, with research demonstrating that elements of the gut microbiome can modulate antitumour immune function, and microbial-derived products have been shown to influence response to chemotherapy. Additionally, microbiome-based 'signatures' have been identified that can act as biomarkers to predict PDAC and improve on currently available serum tumour markers. In this Review, how the microbiome mechanistically influences pancreatic tumours, with a focus on PDAC, and its clinical implications is described using ground-breaking historical and contemporary studies as a framework. The direction for future studies is also discussed.