Ecological Patterns of Gut Microbiota During Elexacaftor/Tezacaftor/Ivacaftor Therapy in Cystic Fibrosis

Putignani, Lorenza; Ciciriello, Fabiana; Turco, Luigia; Del Chierico, Federica; Marangelo, Chiara; Scanu, Matteo; Toto, Francesca; Montemitro, Enza; Bezzerri, Valentino; Fiscarelli, Ersilia; Lucidi, Vincenzina; Fiocchi, Alessandro; Alghisi, Federico; Cutrera, Renato

doi:10.3390/microorganisms14092053

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Open AccessArticle

Ecological Patterns of Gut Microbiota During Elexacaftor/Tezacaftor/Ivacaftor Therapy in Cystic Fibrosis

by

Lorenza Putignani

^1,2,*

,

Fabiana Ciciriello

^3,†

,

Luigia Turco

^4,†

,

Federica Del Chierico

⁴

,

Chiara Marangelo

⁴

,

Matteo Scanu

⁴

,

Francesca Toto

⁴

,

Enza Montemitro

³

,

Valentino Bezzerri

^2,5

,

Ersilia Fiscarelli

⁶,

Vincenzina Lucidi

⁷,

Alessandro Fiocchi

⁸

,

Federico Alghisi

³

and

Renato Cutrera

^3,*

¹

Unit of Microbiomics and Unit of Research of Microbiome, Bambino Gesù Children’s Hospital, IRCCS, 00146 Rome, Italy

²

Department of Life Science, Health and Health Professions, Link Campus University, 00165 Rome, Italy

³

Pneumology and Cystic Fibrosis Unit, Bambino Gesù Children’s Hospital, IRCCS, Piazza Di Sant’Onofrio, 4, 00165 Rome, Italy

⁴

Unit of Research of Microbiome, Bambino Gesù Children’s Hospital, IRCCS, 00146 Rome, Italy

⁵

Cystic Fibrosis Center, Azienda Ospedaliera Universitaria Integrata, 37126 Verona, Italy

⁶

Cystic Fibrosis Microbiology, Bambino Gesù Children’s Hospital, IRCCS, 00146 Rome, Italy

⁷

Cystic Fibrosis Unit, Bambino Gesù Children’s Hospital, IRCCS, Piazza Di Sant’ Onofrio, 4, 00165 Rome, Italy

⁸

Allergy Diseases Research Area, Pediatric Allergology Unit, Bambino Gesù Children’s Hospital, IRCCS, 00146 Rome, Italy

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Microorganisms 2026, 14(9), 2053; https://doi.org/10.3390/microorganisms14092053

Submission received: 3 August 2026 / Revised: 9 September 2026 / Accepted: 10 September 2026 / Published: 14 September 2026

(This article belongs to the Special Issue State-of-the-Art Gut Microbiota in Italy (2025, 2026))

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Abstract

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' GM before therapy (T0), and after 6 (T1) and 12 months (T2). Patients’ stools were analyzed using 16S rRNA metataxonomy, and GM profiling was characterized by alpha diversity, performed using the Shannon–Weiner, Simpson, and Chao1 indices; beta diversity, based on Bray–Curtis 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.

Keywords: cystic fibrosis (CF); gut microbiota (GM); elexacaftor/tezacaftor/ivacaftor (ETI); microbial ecological perturbations

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MDPI and ACS Style

Putignani, L.; Ciciriello, F.; Turco, L.; Del Chierico, F.; Marangelo, C.; Scanu, M.; Toto, F.; Montemitro, E.; Bezzerri, V.; Fiscarelli, E.; et al. Ecological Patterns of Gut Microbiota During Elexacaftor/Tezacaftor/Ivacaftor Therapy in Cystic Fibrosis. Microorganisms 2026, 14, 2053. https://doi.org/10.3390/microorganisms14092053

AMA Style

Putignani L, Ciciriello F, Turco L, Del Chierico F, Marangelo C, Scanu M, Toto F, Montemitro E, Bezzerri V, Fiscarelli E, et al. Ecological Patterns of Gut Microbiota During Elexacaftor/Tezacaftor/Ivacaftor Therapy in Cystic Fibrosis. Microorganisms. 2026; 14(9):2053. https://doi.org/10.3390/microorganisms14092053

Chicago/Turabian Style

Putignani, Lorenza, Fabiana Ciciriello, Luigia Turco, Federica Del Chierico, Chiara Marangelo, Matteo Scanu, Francesca Toto, Enza Montemitro, Valentino Bezzerri, Ersilia Fiscarelli, and et al. 2026. "Ecological Patterns of Gut Microbiota During Elexacaftor/Tezacaftor/Ivacaftor Therapy in Cystic Fibrosis" Microorganisms 14, no. 9: 2053. https://doi.org/10.3390/microorganisms14092053

APA Style

Putignani, L., Ciciriello, F., Turco, L., Del Chierico, F., Marangelo, C., Scanu, M., Toto, F., Montemitro, E., Bezzerri, V., Fiscarelli, E., Lucidi, V., Fiocchi, A., Alghisi, F., & Cutrera, R. (2026). Ecological Patterns of Gut Microbiota During Elexacaftor/Tezacaftor/Ivacaftor Therapy in Cystic Fibrosis. Microorganisms, 14(9), 2053. https://doi.org/10.3390/microorganisms14092053

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Ecological Patterns of Gut Microbiota During Elexacaftor/Tezacaftor/Ivacaftor Therapy in Cystic Fibrosis

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