Evidence map›Paper›PMID 40483244›Full record

Observational studyJournal of cystic fibrosis : official journal of the European Cystic Fibrosis Society2025

Fecal microbiota changes in people with cystic fibrosis after 6 months of elexacaftor/tezacaftor/ivacaftor: Findings from the promise study.

Jennifer T Duong, Hillary S Hayden, Adrian J Verster, Christopher E Pope, Carson Miller, Kelsi Penewit, Stephen J Salipante, Steven M Rowe, George M Solomon, David Nichols and 4 more

Registry-linked trialAbstract readMulticenter StudyObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04038047 (A Prospective Study to Evaluate Biological and Clinical Effects of Significantly Corrected CFTR Function), which is not on this map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04038047 completednot on this map

A Prospective Study to Evaluate Biological and Clinical Effects of Significantly Corrected CFTR Function (The PROMISE Study)

TypeobservationalSponsorNicole HamblettRan2019 to 2024Enrolled490ConditionsCystic Fibrosis
3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Observational
  5. Article
  6. Review
  7. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Jennifer T DuongDepartment of Pediatrics, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, University of California San Francisco School of Medicine, San Francisco, CA, USA. Electronic address: Jennifer.duong@ucsf.edu.
Hillary S HaydenDepartment of Microbiology, University of Washington School of Medicine, Seattle, WA, USA.
Adrian J VersterPythia Informatics, Ottawa, Canada.
Christopher E PopeDepartment of Microbiology, University of Washington School of Medicine, Seattle, WA, USA.
Carson MillerDepartment of Microbiology, University of Washington School of Medicine, Seattle, WA, USA.
Kelsi PenewitDepartment of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, USA.
Stephen J SalipanteDepartment of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, USA.
Steven M RoweDepartment of Medicine and the Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL, USA and CF Foundation, Bethesda, MD, USA.
George M SolomonDepartment of Medicine and the Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL, USA and CF Foundation, Bethesda, MD, USA.
David NicholsCF Foundation, Bethesda, MD, USA and University of Washington School of Medicine, Seattle, WA, USA.
Andrea KellyDepartment of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Sarah Jane SchwarzenbergDepartment of Pediatrics, University of Minnesota Masonic Children's Hospital, Minneapolis, MN, USA.
Steven D FreedmanBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Lucas R HoffmanDepartment of Microbiology and Department of Pediatrics, Division of Pulmonary and Sleep Medicine, University of Washington School of Medicine, Seattle, WA, USA.

Funding

Translational Research Center to Expedite Novel Therapies in Cystic FibrosisP30DK089507 · NIDDK · SEATTLE CHILDREN'S HOSPITAL · PI PRADEEP k SINGH · 2010 to 2026
$21.4M
Patient-oriented microbiome and advanced culture approaches to identifying the microbial determinants of chronic pediatric diseaseK24HL141669 · NHLBI · UNIVERSITY OF WASHINGTON · PI Lucas R Hoffman · 2018 to 2026
$929k
NHLBI NIH HHS K24 HL141669NIDDK NIH HHS P30 DK089507
6 · The paper itself

Abstract

backgroundPeople with cystic fibrosis (PwCF) often have fecal dysbioses relative to those without CF, characterized by increased pro-inflammatory microbiota and gastrointestinal (GI) inflammation as measured by fecal calprotectin, suggesting that inflammation contributes to CF GI disease. The multicenter observational PROMISE study (NCT04038047) found that calprotectin decreased in PwCF treated with elexacaftor/tezacaftor/ivacaftor (ETI). To better understand the dynamics between fecal dysbiosis and GI inflammation, we characterized the microbiomes of fecal samples from PROMISE and the relationships with calprotectin before, 1-month post, and 6-months post ETI.

methodsFecal microbiota from participants ≥12 y/o were determined by shotgun metagenomic sequencing with random forest modeling and multivariate linear regression analysis to define relationships between microbiota, calprotectin, and deltaF508 genotype before and after ETI.

resultsWe analyzed 345 samples from 124 participants. At baseline, we observed community-level differences in the fecal microbiota among participants with abnormal compared to normal calprotectin. With ETI, the relative abundances of 7 bacterial species - Escherichia coli, Staphylococcus aureus, Clostridium scindens, Enterocloster clostridioformis, Clostridium butyricum, Anaeroglobus geminatus, and Ruminococcus gnavus - decreased significantly, correlating with calprotectin decrease. We detected community-level differences in the fecal microbiota based on CFTR genotype and a distinct pattern of microbiota change in F508del homozygous compared to heterozygous participants after ETI.

conclusionsWe identified 7 species for which fecal abundances decreased with ETI and correlated with calprotectin decrease, supporting a close relationship between fecal microbiota and inflammation in PwCF. Future work will define these relationships with metabolites and GI symptoms during long-term ETI therapy.

Indexed as

AminophenolsBenzodioxolesCystic FibrosisDysbiosisFecesGastrointestinal MicrobiomeIndolesPyrazolesPyridinesQuinolonesAdolescentAdultChloride Channel AgonistsDrug CombinationsFemaleHumansAminophenolsBenzodioxolesChloride Channel AgonistsDrug CombinationselexacaftorIndolesLeukocyte L1 Antigen ComplexPyrazolesPyridinesPyrrolidinesQuinolonestezacaftor, ivacaftor drug combinationDysbiosisElexacaftor/tezacaftor/ivacaftorFecal calprotectinFecal microbiome

Identifiers

PMID40483244
PMCPMC12393131

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.