Pancreatic Exocrine Insufficiency and the Gut Microbiome in Pancreatic Cancer: A Target for Future Diagnostic Tests and Therapies?

SIMPLE SUMMARY: It is now thought that bacteria in the gut and tumour of patients with pancreatic cancer play an important role in the growth of the cancer and its sensitivity to chemotherapy. It has been shown that pancreatic exocrine insufficiency (PEI), common in pancreatic cancer patients, is linked to poorer outcomes. Conversely, it has also been demonstrated that treatment with pancreatic enzyme replacement therapy (PERT) can improve survival in pancreatic cancer patients. The reasons for this are not fully understood, but it is possible that PEI alters the gut and tumour microbiome of pancreatic cancer patients towards a less favourable composition, whereas PERT can reverse these changes and make the gut and tumour microbiome more favourable. If true, this could represent an opportunity for the development of new diagnostic tests and therapies for pancreatic cancer, which remains one of the deadliest cancers. ABSTRACT: Pancreatic exocrine insufficiency (PEI) is common amongst pancreatic cancer patients and is associated with poorer treatment outcomes. Pancreatic enzyme replacement therapy (PERT) is known to improve outcomes in pancreatic cancer, but the mechanisms are not fully understood. The aim of this narrative literature review is to summarise the current evidence linking PEI with microbiome dysbiosis, assess how microbiome composition may be impacted by PERT treatment, and look towards possible future diagnostic and therapeutic targets in this area. Early evidence in the literature reveals that there are complex mechanisms by which pancreatic secretions modulate the gut microbiome, so when these are disturbed, as in PEI, gut microbiome dysbiosis occurs. PERT has been shown to return the gut microbiome towards normal, so called rebiosis, in animal studies. Gut microbiome dysbiosis has multiple downstream effects in pancreatic cancer such as modulation of the immune response and the response to chemotherapeutic agents. It therefore represents a possible future target for future therapies. In conclusion, it is likely that the gut microbiome of pancreatic cancer patients with PEI exhibits dysbiosis and that this may potentially be reversible with PERT. However, further human studies are required to determine if this is indeed the case.