Microbiota in the Natural History of Pancreatic Cancer. From Predisposition to Therapy

Simple Summary Pancreatic cancer is still burdened with a severe prognosis, despite advances in the diagnosis and surgical management of this disease. The gut microbiome is gaining increasing interest in the development and management in this setting. The intent of our review is to provide a comprehensive review for researchers and clinicians in the field to fully understand the role of the gut microbiome in the history of pancreatic cancer. We analyzed current literature from pre-cancerous conditions to cancer characteristics and how this may alter the therapeutic approach. Evidence and concerns can guide future research in this area. Early microbiome insights came from gut microbes and their role among intestinal and extraintestinal disease. The latest evidence suggests that the microbiota is a true organ, capable of several interactions throughout the digestive system, attracting specific interest in the biliopancreatic district. Despite advances in diagnostics over the last few decades and improvements in the management of this disease, pancreatic cancer is still a common cause of cancer death. Microbiota can influence the development of precancerous disease predisposing to pancreatic cancer (PC). At the same time, neoplastic tissue shows specific characteristics in terms of diversity and phenotype, determining the short- and long-term prognosis. Considering the above information, a role for microbiota has also been hypothesized in the different phases of the PC approach, providing future revolutionary therapeutic insights. Microbiota-modulating therapies could open new issues in the therapeutic landscape. The aim of this narrative review is to assess the most updated evidence on microbiome in all the steps regarding pancreatic adenocarcinoma, from early development to response to antineoplastic therapy and long-term prognosis.