WS08.03: Remodelling of cystic fibrosis respiratory microbiota in response to extended elexacaftor/tezacaftor/ivacaftor therapy

H. Gavillet; L. Hatfield; M. Hardman; G.G. Einarsson; C.S. Thornton; M.D. Parkins; J. Duckers; J.M. Bomberger; Y. Hilliam; S.E. Lee; R.W. Lord; A. Jones; A. Horsley; T.W.V. Daniels; C.C. Teneback; M.J. Wargo; K. Schutz; D.W. Rivett; C. van der Gast

doi:10.1016/j.jcf.2025.03.536

Abstract

Objectives

The introduction of the highly effective CFTR modulator Elexacaftor/Tezacaftor/Ivacaftor (ETI) has revolutionised clinical outcomes for adults with CF (awCF) eligible for treatment. Despite this little is understood about the long-term impact of ETI on the respiratory microbiota in awCF. In this multi-centre study, we investigated changes to the respiratory microbiota of awCF from before onset of ETI therapy to on-ETI therapy of up to 3 years.

Methods

Respiratory samples were collected from 303 awCF from 6 centres in the UK (Cardiff, Manchester, & Southampton), Canada (Calgary), and USA (Dartmouth & Vermont). This consisted of pre-ETI samples stratified to severe, moderate, and mild disease groups based on %FEV1, and on-ETI samples taken at approximately 6 months, 1, 2, & 3 years. Samples from 11 non-CF healthy participants were included as a comparator group. Microbiota sequencing was performed on all samples.

Results

Microbiota diversity increased with therapy duration. With diversity at years 2 and 3 being comparable (P>0.05) to that observed in the mild disease pre-ETI and healthy groups. Microbiota composition became increasingly similar to mild CF/healthy groups with increasing therapy duration but was still significantly different (P<0.05) at 3 years. Dominance of CF pathogens reduced with therapy duration, with a shift to microbiota characterised by strict anaerobes associated with better clinical outcomes. Despite the reduction in abundance many CF pathogens still persisted.

Conclusions

Long-term ETI therapy resulted in positive changes in the respiratory microbiota, typically associated with better clinical outcomes and microbiota more closely resembling mild CF/healthy microbiota. Despite a positive trajectory towards a healthy-like microbiota, we posit that progression in awCF is impeded by the cumulative effects of progressive airway and lung parenchymal damage, along with the impacts of long-term and continued antibiotic therapy.

Original language	English
Pages (from-to)	S16-S16
Number of pages	1
Journal	Journal of Cystic Fibrosis
Volume	24
Issue number	Supplement 1
Early online date	3 Jun 2025
DOIs	https://doi.org/10.1016/j.jcf.2025.03.536
Publication status	Published - Jun 2025
Event	48th European Cystic Fibrosis Conference - Allianz MiCo, Milan, Italy Duration: 4 Jun 2025 → 7 Jun 2025 https://www.ecfs.eu/milan2025

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1016/j.jcf.2025.03.536

Remodelling of cystic fibrosis respiratory microbiota in response to extended elexacaftor–tezacaftor–ivacaftor therapy
van der Gast, C., Gavillet, H., Hatfield, L. R., Hardman, M., Marsh, R., Einarsson, G. G., Thornton, C. S., Parkins, M. D., Duckers, J., Bomberger, J. M., Hilliam, Y., Lee, S. E., Lord, R. W., Jones, A., Horsley, A., Daniels, T. W. V., Teneback, C. C. & Rivett, D. W., 30 May 2026, (E-pub ahead of print) In: Microbiome.
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Gavillet, H., Hatfield, L., Hardman, M., Einarsson, G. G., Thornton, C. S., Parkins, M. D., Duckers, J., Bomberger, J. M., Hilliam, Y., Lee, S. E., Lord, R. W., Jones, A., Horsley, A., Daniels, T. W. V., Teneback, C. C., Wargo, M. J., Schutz, K., Rivett, D. W., & van der Gast, C. (2025). WS08.03: Remodelling of cystic fibrosis respiratory microbiota in response to extended elexacaftor/tezacaftor/ivacaftor therapy. Journal of Cystic Fibrosis, 24(Supplement 1), S16-S16. https://doi.org/10.1016/j.jcf.2025.03.536

@article{1602ad7b7ba54dbea39c7db792a67d21,

title = "WS08.03: Remodelling of cystic fibrosis respiratory microbiota in response to extended elexacaftor/tezacaftor/ivacaftor therapy",

abstract = "ObjectivesThe introduction of the highly effective CFTR modulator Elexacaftor/Tezacaftor/Ivacaftor (ETI) has revolutionised clinical outcomes for adults with CF (awCF) eligible for treatment. Despite this little is understood about the long-term impact of ETI on the respiratory microbiota in awCF. In this multi-centre study, we investigated changes to the respiratory microbiota of awCF from before onset of ETI therapy to on-ETI therapy of up to 3 years.MethodsRespiratory samples were collected from 303 awCF from 6 centres in the UK (Cardiff, Manchester, \& Southampton), Canada (Calgary), and USA (Dartmouth \& Vermont). This consisted of pre-ETI samples stratified to severe, moderate, and mild disease groups based on \%FEV1, and on-ETI samples taken at approximately 6 months, 1, 2, \& 3 years. Samples from 11 non-CF healthy participants were included as a comparator group. Microbiota sequencing was performed on all samples.ResultsMicrobiota diversity increased with therapy duration. With diversity at years 2 and 3 being comparable (P>0.05) to that observed in the mild disease pre-ETI and healthy groups. Microbiota composition became increasingly similar to mild CF/healthy groups with increasing therapy duration but was still significantly different (P<0.05) at 3 years. Dominance of CF pathogens reduced with therapy duration, with a shift to microbiota characterised by strict anaerobes associated with better clinical outcomes. Despite the reduction in abundance many CF pathogens still persisted.ConclusionsLong-term ETI therapy resulted in positive changes in the respiratory microbiota, typically associated with better clinical outcomes and microbiota more closely resembling mild CF/healthy microbiota. Despite a positive trajectory towards a healthy-like microbiota, we posit that progression in awCF is impeded by the cumulative effects of progressive airway and lung parenchymal damage, along with the impacts of long-term and continued antibiotic therapy.",

author = "H. Gavillet and L. Hatfield and M. Hardman and G.G. Einarsson and C.S. Thornton and M.D. Parkins and J. Duckers and J.M. Bomberger and Y. Hilliam and S.E. Lee and R.W. Lord and A. Jones and A. Horsley and T.W.V. Daniels and C.C. Teneback and M.J. Wargo and K. Schutz and D.W. Rivett and \{van der Gast\}, C.",

year = "2025",

month = jun,

doi = "10.1016/j.jcf.2025.03.536",

language = "English",

volume = "24",

pages = "S16--S16",

journal = "Journal of Cystic Fibrosis",

issn = "1569-1993",

publisher = "Elsevier B.V.",

number = "Supplement 1",

note = "48th European Cystic Fibrosis Conference ; Conference date: 04-06-2025 Through 07-06-2025",

url = "https://www.ecfs.eu/milan2025",

}

Gavillet, H, Hatfield, L, Hardman, M, Einarsson, GG, Thornton, CS, Parkins, MD, Duckers, J, Bomberger, JM, Hilliam, Y, Lee, SE, Lord, RW, Jones, A, Horsley, A, Daniels, TWV, Teneback, CC, Wargo, MJ, Schutz, K, Rivett, DW & van der Gast, C 2025, 'WS08.03: Remodelling of cystic fibrosis respiratory microbiota in response to extended elexacaftor/tezacaftor/ivacaftor therapy', Journal of Cystic Fibrosis, vol. 24, no. Supplement 1, pp. S16-S16. https://doi.org/10.1016/j.jcf.2025.03.536

TY - JOUR

T1 - WS08.03: Remodelling of cystic fibrosis respiratory microbiota in response to extended elexacaftor/tezacaftor/ivacaftor therapy

AU - Gavillet, H.

AU - Hatfield, L.

AU - Hardman, M.

AU - Einarsson, G.G.

AU - Thornton, C.S.

AU - Parkins, M.D.

AU - Duckers, J.

AU - Bomberger, J.M.

AU - Hilliam, Y.

AU - Lee, S.E.

AU - Lord, R.W.

AU - Jones, A.

AU - Horsley, A.

AU - Daniels, T.W.V.

AU - Teneback, C.C.

AU - Wargo, M.J.

AU - Schutz, K.

AU - Rivett, D.W.

AU - van der Gast, C.

PY - 2025/6

Y1 - 2025/6

N2 - ObjectivesThe introduction of the highly effective CFTR modulator Elexacaftor/Tezacaftor/Ivacaftor (ETI) has revolutionised clinical outcomes for adults with CF (awCF) eligible for treatment. Despite this little is understood about the long-term impact of ETI on the respiratory microbiota in awCF. In this multi-centre study, we investigated changes to the respiratory microbiota of awCF from before onset of ETI therapy to on-ETI therapy of up to 3 years.MethodsRespiratory samples were collected from 303 awCF from 6 centres in the UK (Cardiff, Manchester, & Southampton), Canada (Calgary), and USA (Dartmouth & Vermont). This consisted of pre-ETI samples stratified to severe, moderate, and mild disease groups based on %FEV1, and on-ETI samples taken at approximately 6 months, 1, 2, & 3 years. Samples from 11 non-CF healthy participants were included as a comparator group. Microbiota sequencing was performed on all samples.ResultsMicrobiota diversity increased with therapy duration. With diversity at years 2 and 3 being comparable (P>0.05) to that observed in the mild disease pre-ETI and healthy groups. Microbiota composition became increasingly similar to mild CF/healthy groups with increasing therapy duration but was still significantly different (P<0.05) at 3 years. Dominance of CF pathogens reduced with therapy duration, with a shift to microbiota characterised by strict anaerobes associated with better clinical outcomes. Despite the reduction in abundance many CF pathogens still persisted.ConclusionsLong-term ETI therapy resulted in positive changes in the respiratory microbiota, typically associated with better clinical outcomes and microbiota more closely resembling mild CF/healthy microbiota. Despite a positive trajectory towards a healthy-like microbiota, we posit that progression in awCF is impeded by the cumulative effects of progressive airway and lung parenchymal damage, along with the impacts of long-term and continued antibiotic therapy.

AB - ObjectivesThe introduction of the highly effective CFTR modulator Elexacaftor/Tezacaftor/Ivacaftor (ETI) has revolutionised clinical outcomes for adults with CF (awCF) eligible for treatment. Despite this little is understood about the long-term impact of ETI on the respiratory microbiota in awCF. In this multi-centre study, we investigated changes to the respiratory microbiota of awCF from before onset of ETI therapy to on-ETI therapy of up to 3 years.MethodsRespiratory samples were collected from 303 awCF from 6 centres in the UK (Cardiff, Manchester, & Southampton), Canada (Calgary), and USA (Dartmouth & Vermont). This consisted of pre-ETI samples stratified to severe, moderate, and mild disease groups based on %FEV1, and on-ETI samples taken at approximately 6 months, 1, 2, & 3 years. Samples from 11 non-CF healthy participants were included as a comparator group. Microbiota sequencing was performed on all samples.ResultsMicrobiota diversity increased with therapy duration. With diversity at years 2 and 3 being comparable (P>0.05) to that observed in the mild disease pre-ETI and healthy groups. Microbiota composition became increasingly similar to mild CF/healthy groups with increasing therapy duration but was still significantly different (P<0.05) at 3 years. Dominance of CF pathogens reduced with therapy duration, with a shift to microbiota characterised by strict anaerobes associated with better clinical outcomes. Despite the reduction in abundance many CF pathogens still persisted.ConclusionsLong-term ETI therapy resulted in positive changes in the respiratory microbiota, typically associated with better clinical outcomes and microbiota more closely resembling mild CF/healthy microbiota. Despite a positive trajectory towards a healthy-like microbiota, we posit that progression in awCF is impeded by the cumulative effects of progressive airway and lung parenchymal damage, along with the impacts of long-term and continued antibiotic therapy.

U2 - 10.1016/j.jcf.2025.03.536

DO - 10.1016/j.jcf.2025.03.536

M3 - Meeting Abstract

SN - 1569-1993

VL - 24

SP - S16-S16

JO - Journal of Cystic Fibrosis

JF - Journal of Cystic Fibrosis

IS - Supplement 1

T2 - 48th European Cystic Fibrosis Conference

Y2 - 4 June 2025 through 7 June 2025

ER -

WS08.03: Remodelling of cystic fibrosis respiratory microbiota in response to extended elexacaftor/tezacaftor/ivacaftor therapy

Abstract

UN SDGs

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Research output

Remodelling of cystic fibrosis respiratory microbiota in response to extended elexacaftor–tezacaftor–ivacaftor therapy

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