Gut microbiome as a response marker for pancreatic enzyme replacement therapy in a porcine model of exocrine pancreas in
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Microbial Cell Factories Open Access
RESEARCH
Gut microbiome as a response marker for pancreatic enzyme replacement therapy in a porcine model of exocrine pancreas insufficiency Sabrina Ritz1, Daniela Hahn1, Haleluya T. Wami2, Karin Tegelkamp2, Ulrich Dobrindt2 and Juergen Schnekenburger1*
Abstract Background: 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). Here, we analyzed the effects of EPI and PERT on the gut microbiome in the model of pancreatic duct ligated minipigs. Results: The 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. Conclusion: These 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. Keywords: Exocrine pancreatic insufficiency, Gut microbiota, α-diversity, β-diversity, Pancreatic enzyme replacement therapy Background 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%. It can be induced by *Correspondence: schnekenburger@uni‑muenster.de 1 Biomedical Technology Center of the Medical Faculty, University of Muenster, Mendelstrasse 17, 48149 Muenster, Germany Full list of author information is available at the end of the article
several disorders like cystic fibrosis (CF), acute (AP) or chronic pancreatitis (CP), pancreatic cancer, diabetes mellitus or as a complication of gastrointestinal surgery [1–5]. EPI patients are affected by weight loss and malnutrition [4, 6]. EPI symptoms significantly impair the quality of life, and malnutrition especially of fat soluble vitamins subsequently may result in other severe diseases like osteoporosis, osteopenia or low-trauma fracture [7, 8]. Disease progression, severity and occurring comorbid
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