Gut microbiome as a response marker for pancreatic enzyme replacement therapy in a porcine model of exocrine pancreas insufficiency

Sabrina Ritz,Daniela Hahn,Ulrich Dobrindt,Juergen Schnekenburger,Haleluya T. Wami,Karin Tegelkamp

doi:10.1186/s12934-020-01482-2

Abstract

BackgroundExocrine pancreatic insufficiency (EPI) is characterized by the loss of active pancreatic enzymes and a resulting severely reduced food digestion. EPI therapy requires orally applied pancreatic enzyme replacement. The gut microbiome is a known mediator of intestinal diseases and may influence the outcome of EPI and the effects of a pancreatic enzyme replacement therapy (PERT). Here, we analyzed the effects of EPI and PERT on the gut microbiome in the model of pancreatic duct ligated minipigs.ResultsThe microbial community composition in pig feces was analyzed by next generation sequencing of 16S rRNA amplicons. The data were evaluated for α- and β-diversity changes and changes at the different Operational Taxonomic Unit (OTU) levels by Shannon–Wiener and inverse Simpson index calculation as well as by Principal Coordinates Analysis based on Bray–Curtis dissimilarity. Microbial α-diversity was reduced after EPI induction and reverted to nearly healthy state after PERT. Analysis of microbial composition and β-diversity showed distinctive clusters of the three study groups and a change towards a composition comparable to healthy animals upon PERT. The relative abundance of possible pathobionts like Escherichia/Shigella, Acinetobacter or Stenotrophomonas was reduced by PERT.ConclusionThese data demonstrate that EPI-induced dysbiosis could be reverted by PERT to a nearly healthy state. Elevated α-diversity and the reduction of bacterial overgrowth after PERT promises benefits for EPI patients. Non-invasive microbiome studies may be useful for EPI therapy monitoring and as marker for response to PERT.

Highlights

Exocrine pancreatic insufficiency (EPI) is characterized by the loss of active pancreatic enzymes and a resulting severely reduced food digestion
Other effects observed in cystic fibrosis (CF) as well as in chronic pancreatitis (CP), are small intestinal bacterial overgrowth (SIBO) and changes in the microbial gut composition that in turn leads to worsening of the symptoms [10, 11]
The α-diversity Shannon–Wiener index as well as the inverse Simpson index were estimated from the number of observed Operational Taxonomic Units (OTUs)

Summary

Introduction

Exocrine pancreatic insufficiency (EPI) is characterized by the loss of active pancreatic enzymes and a resulting severely reduced food digestion. EPI therapy requires orally applied pancreatic enzyme replacement. The gut microbiome is a known mediator of intestinal diseases and may influence the outcome of EPI and the effects of a pancreatic enzyme replacement therapy (PERT). Exocrine pancreatic insufficiency (EPI) is a severe impairment of food digestion as a result of a loss of active pancreatic enzymes. EPI is defined as a decline of pancreatic enzyme release to less than 5–10%. EPI treatment is mainly based on the orally applied pancreatic enzyme replacement therapy (PERT) [6, 9]. SIBO and the associated reduction of microbial diversity (i.e. α-diversity) as well as loss of beneficial bacteria are hallmarks of existing dysbiosis [13]

Objectives

Methods

Results

Discussion

Conclusion