{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T17:51:09Z","timestamp":1792086669053,"version":"4.4.0"},"reference-count":71,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,6]],"date-time":"2025-09-06T00:00:00Z","timestamp":1757116800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Mutations in the CFTR genes causing cystic fibrosis (CF) are associated with the presence of thick, viscous mucus and the formation of biofilms in the gastrointestinal tract (GI) that impair intestinal homeostasis, triggering chronic inflammation, epithelial barrier dysfunction, and changes in the composition and activity of the gut microbiota. CFTR protein modulators represent a promising approach to enhancing lower GI function in patients with CF. The aim of the review is to present the complex relationships between the presence of CFTR gene mutations and the gut microbiota dysbiosis in patients with cystic fibrosis. Mutations in the CFTR gene, the molecular basis of cystic fibrosis (CF), disrupt epithelial ion transport and profoundly alter the gastrointestinal environment. Defective chloride and bicarbonate secretion leads to dehydration of the mucosal layer, increased mucus viscosity, and the formation of biofilms that favour microbial persistence, which together promote gut microbiota dysbiosis. This dysbiotic state contributes to impaired epithelial barrier function, chronic intestinal inflammation, and abnormal immune activation, thereby reinforcing disease progression. The interplay between CFTR dysfunction and microbial imbalance appears to be bidirectional, as dysbiosis may further exacerbate epithelial stress and inflammatory signalling. Therapeutic interventions with CFTR protein modulators offer the potential to partially restore epithelial physiology, improve mucus hydration, and foster a microbial milieu more consistent with intestinal homeostasis. The aim of this review is to elucidate the complex relationships between CFTR gene mutations and gut microbiota dysbiosis in patients with cystic fibrosis, with a particular emphasis on the clinical implications of these interactions and their potential to inform novel therapeutic strategies.<\/jats:p>","DOI":"10.3390\/genes16091049","type":"journal-article","created":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T08:06:32Z","timestamp":1757318792000},"page":"1049","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Gut Dysbiosis Driven by CFTR Gene Mutations in Cystic Fibrosis Patients: From Genetic Disruption to Multisystem Consequences and Microbiota Modulation"],"prefix":"10.3390","volume":"16","author":[{"given":"Natalia","family":"Paw\u0142owska","sequence":"first","affiliation":[{"name":"Institute of Human Biology and Evolution, Faculty of Biology, Adam Mickiewicz University, 61-614 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5895-9754","authenticated-orcid":false,"given":"Magdalena","family":"Durda-Masny","sequence":"additional","affiliation":[{"name":"Institute of Human Biology and Evolution, Faculty of Biology, Adam Mickiewicz University, 61-614 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szczepan","family":"Cofta","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Allergology and Respiratory Oncology, Poznan University of Medical Sciences, 60-569 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria","family":"Springer","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Allergology and Respiratory Oncology, Poznan University of Medical Sciences, 60-569 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7516-5019","authenticated-orcid":false,"given":"Anita","family":"Szwed","sequence":"additional","affiliation":[{"name":"Institute of Human Biology and Evolution, Faculty of Biology, Adam Mickiewicz University, 61-614 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,6]]},"reference":[{"key":"ref_1","first-page":"584","article-title":"Cystic fibrosis: Current concepts","volume":"78","author":"Reyes","year":"2021","journal-title":"Bolet\u00edn M\u00e9dico Hosp. 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