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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\u00a0the effects of EPI and PERT on the gut microbiome in the model of pancreatic duct ligated minipigs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The microbial community composition in pig feces was\u00a0analyzed by next generation sequencing of 16S rRNA amplicons. The data were evaluated for \u03b1- and \u03b2-diversity changes and changes at the different Operational Taxonomic Unit (OTU) levels by Shannon\u2013Wiener and inverse Simpson index calculation as well as by Principal Coordinates Analysis based on Bray\u2013Curtis dissimilarity. Microbial \u03b1-diversity was reduced after EPI induction and reverted to nearly healthy state after PERT. Analysis of microbial composition and \u03b2-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<jats:italic>Escherichia<\/jats:italic>\/<jats:italic>Shigella<\/jats:italic>,<jats:italic>Acinetobacter<\/jats:italic>or<jats:italic>Stenotrophomonas<\/jats:italic>was reduced by PERT.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These data demonstrate that EPI-induced dysbiosis could be reverted by PERT to a nearly healthy state. Elevated \u03b1-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.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12934-020-01482-2","type":"journal-article","created":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T10:03:49Z","timestamp":1606989829000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Gut microbiome as a response marker for pancreatic enzyme replacement therapy in a porcine model of exocrine pancreas insufficiency"],"prefix":"10.1186","volume":"19","author":[{"given":"Sabrina","family":"Ritz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Hahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haleluya T.","family":"Wami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Tegelkamp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Dobrindt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0199-2908","authenticated-orcid":false,"given":"Juergen","family":"Schnekenburger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,12,3]]},"reference":[{"issue":"1","key":"1482_CR1","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1159\/000501675","volume":"38","author":"A Chaudhary","year":"2020","unstructured":"Chaudhary A, Dominguez-Munoz JE, Layer P, Lerch MM. 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