{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T05:02:20Z","timestamp":1789707740814,"version":"4.0.1"},"reference-count":55,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Cystic fibrosis (CF) is a genetic disorder caused by CFTR gene mutations. The elexacaftor\/tezacaftor\/ivacaftor (ETI) drug combination has markedly improved CF outcomes; however, its impact on gut microbiota (GM) dysbiosis remains poorly investigated. Herein, we examined potential longitudinal effects of ETI treatment on six CF patients\u2019 GM before therapy (T0), and after 6 (T1) and 12 months (T2). Patients\u2019 stools were analyzed using 16S rRNA metataxonomy, and GM profiling was characterized by alpha diversity, performed using the Shannon\u2013Weiner, Simpson, and Chao1 indices; beta diversity, based on Bray\u2013Curtis distance; and taxonomic patterns through multivariate and univariate analyses. A longitudinal exploratory assessment of the GM composition of CF patients at T0, T1, and T2 was performed. At baseline, CF patients displayed a distinct genus-level microbial signature compared with healthy controls, including Veillonella_A, Haemophilus_D_735815, Fusobacterium_C, Ruminococcus_B, and Blautia_A_141780. During ETI treatment, alpha diversity showed no significant transient increase at T1 followed by a decrease at T2. Taxonomic profiles showed marked inter-individual heterogeneity. Exploratory longitudinal analyses, assessed by the Friedman test, identified temporal variation in 11 bacterial genera: CAG-177, Clostridium_AP, Coprococcus_A_121497, Copromonas, and Muricomes_149725, showed a progressive decrease in relative abundance from T0 to T2; Haemophilus_D_734546, Eubacterium_B, Lachnoanaerobaculum, Moraxella_C_651924, and Neisseria_563205 displayed a transient increase at T1, followed by a decrease at T2; and Lactococcus_A_346120 showed a transient decrease at T1 followed by an increase at T2. Progressive depletion and transient changes or recovery of bacterial taxa may only represent a rough idea of the ecological changes in the gut microbiota observed during the course of ETI therapy. Longitudinally studies based on large cohorts of CF patients are mandatory to properly interpret these very preliminary results and to search for actual ETI-induced microbiome effects.<\/jats:p>","DOI":"10.3390\/microorganisms14092053","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T14:15:04Z","timestamp":1789395304000},"page":"2053","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ecological Patterns of Gut Microbiota During Elexacaftor\/Tezacaftor\/Ivacaftor Therapy in Cystic Fibrosis"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0134-2830","authenticated-orcid":false,"given":"Lorenza","family":"Putignani","sequence":"first","affiliation":[{"name":"Unit of Microbiomics and Unit of Research of Microbiome, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00146 Rome, Italy"},{"name":"Department of Life Science, Health and Health Professions, Link Campus University, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1493-9767","authenticated-orcid":false,"given":"Fabiana","family":"Ciciriello","sequence":"additional","affiliation":[{"name":"Pneumology and Cystic Fibrosis Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza Di Sant\u2019Onofrio, 4, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8527-4518","authenticated-orcid":false,"given":"Luigia","family":"Turco","sequence":"additional","affiliation":[{"name":"Unit of Research of Microbiome, Bambino Ges\u00f9 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Children\u2019s Hospital, IRCCS, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6266-2884","authenticated-orcid":false,"given":"Matteo","family":"Scanu","sequence":"additional","affiliation":[{"name":"Unit of Research of Microbiome, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"software","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8976-9013","authenticated-orcid":false,"given":"Francesca","family":"Toto","sequence":"additional","affiliation":[{"name":"Unit of Research of Microbiome, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1759-2896","authenticated-orcid":false,"given":"Enza","family":"Montemitro","sequence":"additional","affiliation":[{"name":"Pneumology and Cystic Fibrosis Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza Di Sant\u2019Onofrio, 4, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6849-4487","authenticated-orcid":false,"given":"Valentino","family":"Bezzerri","sequence":"additional","affiliation":[{"name":"Department of Life Science, Health and Health Professions, Link Campus University, 00165 Rome, Italy"},{"name":"Cystic Fibrosis Center, Azienda Ospedaliera Universitaria Integrata, 37126 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Ersilia","family":"Fiscarelli","sequence":"additional","affiliation":[{"name":"Cystic Fibrosis Microbiology, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Vincenzina","family":"Lucidi","sequence":"additional","affiliation":[{"name":"Cystic Fibrosis Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza Di Sant\u2019 Onofrio, 4, 00165 Rome, 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