{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T22:41:14Z","timestamp":1791844874858,"version":"4.3.4"},"reference-count":57,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T00:00:00Z","timestamp":1740700800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Center","award":["NCN 2017\/27\/B\/NZ5\/02904"],"award-info":[{"award-number":["NCN 2017\/27\/B\/NZ5\/02904"]}]},{"name":"Medical University of Bialystok","award":["NCN 2017\/27\/B\/NZ5\/02904"],"award-info":[{"award-number":["NCN 2017\/27\/B\/NZ5\/02904"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>An association between gut microbiota and the development of pancreatic ductal adenocarcinoma (PDAC) has been previously described. To better understand the bacterial microbiota changes accompanying PDAC promotion and progression stimulated by inflammation and fecal microbiota transplantation (FMT), we investigated stool and pancreatic microbiota by 16s RNA-based metagenomic analysis in mice with inducible acinar transgenic expressions of KrasG12D, and age- and sex-matched control mice that were exposed to inflammatory stimuli and fecal microbiota obtained from mice with PDAC. Time- and inflammatory-dependent stool and pancreatic bacterial composition alterations and stool alpha microbiota diversity reduction were observed only in mice with a Kras mutation that developed advanced pancreatic changes. Stool Actinobacteriota abundance and pancreatic Actinobacteriota and Bifidobacterium abundances increased. In contrast, stool abundance of Firmicutes, Verrucomicrobiota, Spirochaetota, Desulfobacterota, Butyricicoccus, Roseburia, Lachnospiraceae A2, Lachnospiraceae unclassified, and Oscillospiraceae unclassified decreased, and pancreatic detection of Alloprevotella and Oscillospiraceae uncultured was not observed. Furthermore, FMT accelerated tumorigenesis, gradually decreased the stool alpha diversity, and changed the pancreatic and stool microbial composition in mice with a Kras mutation. Specifically, the abundance of Actinobacteriota, Bifidobacterium and Faecalibaculum increased, while the abundance of genera such as Lachnospiraceace A2 and ASF356, Desulfovibrionaceace uncultured, and Roseburia has decreased. In conclusion, pancreatic carcinogenesis in the presence of an oncogenic Kras mutation stimulated by chronic inflammation and FMT dynamically changes the stool and pancreas microbiota. In particular, a decrease in stool microbiota diversity and abundance of bacteria known to be involved in short-fatty acids production were observed. PDAC mouse model can be used for further research on microbiota\u2013PDAC interactions and towards more personalized and effective cancer therapies.<\/jats:p>","DOI":"10.3390\/cells14050361","type":"journal-article","created":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T10:12:33Z","timestamp":1740737553000},"page":"361","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Inflammatory Stimuli and Fecal Microbiota Transplantation Accelerate Pancreatic Carcinogenesis in Transgenic Mice, Accompanied by Changes in the Microbiota Composition"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6577-5796","authenticated-orcid":false,"given":"Agnieszka","family":"\u015awidnicka-Siergiejko","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Internal Medicine, Medical University of Bialystok, 15-276 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0787-1461","authenticated-orcid":false,"given":"Jaros\u0142aw","family":"Daniluk","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Internal Medicine, Medical University of Bialystok, 15-276 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Miniewska","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Medical University of Bialystok, 15-276 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1671-6578","authenticated-orcid":false,"given":"Urszula","family":"Daniluk","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Gastroenterology, Hepatology, Nutrition, Allergology and Pulmonology, Medical University of Bialystok, 15-276 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Guzi\u0144ska-Ustymowicz","sequence":"additional","affiliation":[{"name":"Department of General Pathomorphology, Medical University of Bialystok, 15-276 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2786-7179","authenticated-orcid":false,"given":"Anna","family":"Pryczynicz","sequence":"additional","affiliation":[{"name":"Department of General Pathomorphology, Medical University of Bialystok, 15-276 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milena","family":"D\u0105browska","sequence":"additional","affiliation":[{"name":"Department of Heamatological Diagnostics, Medical University of Bialystok, 15-276 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6949-7508","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"Rusak","sequence":"additional","affiliation":[{"name":"Department of Heamatological Diagnostics, Medical University of Bialystok, 15-276 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3729-0518","authenticated-orcid":false,"given":"Micha\u0142","family":"Ciborowski","sequence":"additional","affiliation":[{"name":"Metabolomics and Proteomics Laboratory, Department of Medical Biochemistry, Clinical Research Centre, Medical University of Bialystok, 15-276 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5996-394X","authenticated-orcid":false,"given":"Andrzej","family":"D\u0105browski","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Internal Medicine, Medical University of Bialystok, 15-276 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16022","DOI":"10.1038\/nrdp.2016.22","article-title":"Pancreatic cancer","volume":"2","author":"Kleeff","year":"2016","journal-title":"Nat. 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