The Effect of Pancreatic Exocrine Insufficiency and Pancreatic Enzyme Replacement Therapy on Gut Microbiome Composition in Pancreatic Disease: A Prospective Cohort Study

Objectives: Increasing evidence demonstrates that pancreatic exocrine insufficiency (PEI) is associated with harmful changes to the gut microbiome. The mainstay of PEI treatment is with pancreatic enzyme replacement therapy (PERT), which has been shown to lead to significant survival benefit in pancreatic disease. The aim of this study was to determine how treatment of PEI with PERT affects gut microbiome composition. Methods: This is a prospective observational cohort study of patients being treated for pancreatic disease at a single centre. PEI status of patients was assessed at the time of recruitment using published diagnostic criteria. Pre-PERT samples were taken before treatment was started and post-PERT samples were taken after at least 4 weeks of treatment. To profile the gut microbiome composition, shotgun metagenomic sequencing was performed with DNA extracted from stool samples. Results: 25 patients with pancreatic disease were included. The abundance of pathogenic bacteria, such as Viridans group Streptococcus and Campylobacter species, was significantly increased in the gut microbiome of patients with PEI compared to those without PEI. Following PERT treatment, analysis of the gut microbiome of treated patients showed a significant reduction in the abundance of multiple pathogenic species, such as those from Viridans group Streptococci , compared to untreated PEI patients. Conclusions: Treatment with PERT leads to significant changes in the gut microbiome composition of patients with pancreatic disease. Changes include a significant reduction in potentially pathogenic bacteria and so may contribute to the survival benefits seen with PERT treatment in pancreatic disease.