Clinical Outcomes of Real-World Kalydeco (CORK) study −Investigating the impact of CFTR potentiation on the intestinalmicrobiota, exocrine pancreatic function and intestinalinflammation prospectively over 12 months

Jennifer Deane, Nicola J Ronan, Grace P O' Callaghan, Fiona Fouhy, Mary C Rea, Orla O' Sullivan, Colin J Hill, Fergus Shanahan, Paul R Ross, Mairead McCarthy, Des M Murphy, Joseph A Eustace, Catherine Stanton, Barry J Plant

    Research output: Contribution to journalArticle

    Abstract

    ObjectivesIvacaftor is effective in the treatment of patients with CF and the G551D gating mutation. We present faecal analysis results of the CORK cohort, a single-centre, adult (n = 20), prospective, longitudinal study of G551D clinical responders (median follow-up 12 months), examining the gut microbiota, exocrine pancreatic function and intestinal inflammation on a 3 monthly basis after commencing treatment.MethodsStool samples pre- and 3 monthly post commencement of ivacaftor in 20 adult patients underwent metagenomic profiling of faecal microbiota. Faecal elastase-1 (FE-1), faecal calprotectin (FC) and faecal lactoferrin (FL) were measured using commercially available ELISA kits.ResultsIvacaftor did not significantly alter gut microbial diversity, as measured by chao1 (p = 0.886). At phylum, family and genus levels significant increases were observed in Bacteroidetes (p = 0.044), Bacteroidaceae (p = 0.021) and Bacteroides (p = 0.021). Significant decreases were observed in Microbacteriaceae (p = 0.003) and Eubacteriaceae (p = 0.014). A significant positive correlation was seen between FEV1 and gut microbiota diversity following treatment (r = 0.4, p = 0.002). No significant difference was measured in levels of FE-1 (p = 0.267), FC (p = 0.406) or FL (p = 0.779).ConclusionIvacaftor therapy has a normalisation effect on the gut microbiota, directing the microbiota towards a non-CF profile. Despite this elevated intestinal inflammation was sustained. Lack of exocrine pancreatic recovery may reflect established exocrine pancreatic dysfunction in an adult cohort. On-going longitudinal prospective data may demonstrate further improvements in the gut health of this cohort.
    LanguageEnglish
    Pages29
    JournalJournal of Cystic Fibrosis
    Volume14
    Issue number1
    DOIs
    Publication statusAccepted/In press - 20 Jun 2015

    Fingerprint

    Leukocyte L1 Antigen Complex
    Lactoferrin
    Pancreatic Elastase
    Microbiota
    Bacteroidaceae
    Bacteroidetes
    Inflammation
    Metagenomics
    Bacteroides
    Therapeutics
    Longitudinal Studies
    Enzyme-Linked Immunosorbent Assay
    Prospective Studies
    Mutation
    ivacaftor
    Health
    Gastrointestinal Microbiome

    Keywords

    • Cystic Fibrosis
    • Gut microbiota
    • Ivacaftor

    Cite this

    Deane, Jennifer ; Ronan, Nicola J ; O' Callaghan, Grace P ; Fouhy, Fiona ; Rea, Mary C ; O' Sullivan, Orla ; Hill, Colin J ; Shanahan, Fergus ; Ross, Paul R ; McCarthy, Mairead ; Murphy, Des M ; Eustace, Joseph A ; Stanton, Catherine ; Plant, Barry J. / Clinical Outcomes of Real-World Kalydeco (CORK) study −Investigating the impact of CFTR potentiation on the intestinalmicrobiota, exocrine pancreatic function and intestinalinflammation prospectively over 12 months. In: Journal of Cystic Fibrosis. 2015 ; Vol. 14, No. 1. pp. 29.
    @article{76579a7f558848bf93bbc4d88b3fd9d8,
    title = "Clinical Outcomes of Real-World Kalydeco (CORK) study −Investigating the impact of CFTR potentiation on the intestinalmicrobiota, exocrine pancreatic function and intestinalinflammation prospectively over 12 months",
    abstract = "ObjectivesIvacaftor is effective in the treatment of patients with CF and the G551D gating mutation. We present faecal analysis results of the CORK cohort, a single-centre, adult (n = 20), prospective, longitudinal study of G551D clinical responders (median follow-up 12 months), examining the gut microbiota, exocrine pancreatic function and intestinal inflammation on a 3 monthly basis after commencing treatment.MethodsStool samples pre- and 3 monthly post commencement of ivacaftor in 20 adult patients underwent metagenomic profiling of faecal microbiota. Faecal elastase-1 (FE-1), faecal calprotectin (FC) and faecal lactoferrin (FL) were measured using commercially available ELISA kits.ResultsIvacaftor did not significantly alter gut microbial diversity, as measured by chao1 (p = 0.886). At phylum, family and genus levels significant increases were observed in Bacteroidetes (p = 0.044), Bacteroidaceae (p = 0.021) and Bacteroides (p = 0.021). Significant decreases were observed in Microbacteriaceae (p = 0.003) and Eubacteriaceae (p = 0.014). A significant positive correlation was seen between FEV1 and gut microbiota diversity following treatment (r = 0.4, p = 0.002). No significant difference was measured in levels of FE-1 (p = 0.267), FC (p = 0.406) or FL (p = 0.779).ConclusionIvacaftor therapy has a normalisation effect on the gut microbiota, directing the microbiota towards a non-CF profile. Despite this elevated intestinal inflammation was sustained. Lack of exocrine pancreatic recovery may reflect established exocrine pancreatic dysfunction in an adult cohort. On-going longitudinal prospective data may demonstrate further improvements in the gut health of this cohort.",
    keywords = "Cystic Fibrosis, Gut microbiota, Ivacaftor",
    author = "Jennifer Deane and Ronan, {Nicola J} and {O' Callaghan}, {Grace P} and Fiona Fouhy and Rea, {Mary C} and {O' Sullivan}, Orla and Hill, {Colin J} and Fergus Shanahan and Ross, {Paul R} and Mairead McCarthy and Murphy, {Des M} and Eustace, {Joseph A} and Catherine Stanton and Plant, {Barry J}",
    year = "2015",
    month = "6",
    day = "20",
    doi = "10.1016/S1569-1993",
    language = "English",
    volume = "14",
    pages = "29",
    journal = "Journal of Cystic Fibrosis",
    issn = "1569-1993",
    publisher = "Elsevier",
    number = "1",

    }

    Deane, J, Ronan, NJ, O' Callaghan, GP, Fouhy, F, Rea, MC, O' Sullivan, O, Hill, CJ, Shanahan, F, Ross, PR, McCarthy, M, Murphy, DM, Eustace, JA, Stanton, C & Plant, BJ 2015, 'Clinical Outcomes of Real-World Kalydeco (CORK) study −Investigating the impact of CFTR potentiation on the intestinalmicrobiota, exocrine pancreatic function and intestinalinflammation prospectively over 12 months', Journal of Cystic Fibrosis, vol. 14, no. 1, pp. 29. https://doi.org/10.1016/S1569-1993

    Clinical Outcomes of Real-World Kalydeco (CORK) study −Investigating the impact of CFTR potentiation on the intestinalmicrobiota, exocrine pancreatic function and intestinalinflammation prospectively over 12 months. / Deane, Jennifer; Ronan, Nicola J; O' Callaghan, Grace P; Fouhy, Fiona; Rea, Mary C; O' Sullivan, Orla; Hill, Colin J; Shanahan, Fergus; Ross, Paul R; McCarthy, Mairead; Murphy, Des M; Eustace, Joseph A; Stanton, Catherine; Plant, Barry J.

    In: Journal of Cystic Fibrosis, Vol. 14, No. 1, 20.06.2015, p. 29.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Clinical Outcomes of Real-World Kalydeco (CORK) study −Investigating the impact of CFTR potentiation on the intestinalmicrobiota, exocrine pancreatic function and intestinalinflammation prospectively over 12 months

    AU - Deane, Jennifer

    AU - Ronan, Nicola J

    AU - O' Callaghan, Grace P

    AU - Fouhy, Fiona

    AU - Rea, Mary C

    AU - O' Sullivan, Orla

    AU - Hill, Colin J

    AU - Shanahan, Fergus

    AU - Ross, Paul R

    AU - McCarthy, Mairead

    AU - Murphy, Des M

    AU - Eustace, Joseph A

    AU - Stanton, Catherine

    AU - Plant, Barry J

    PY - 2015/6/20

    Y1 - 2015/6/20

    N2 - ObjectivesIvacaftor is effective in the treatment of patients with CF and the G551D gating mutation. We present faecal analysis results of the CORK cohort, a single-centre, adult (n = 20), prospective, longitudinal study of G551D clinical responders (median follow-up 12 months), examining the gut microbiota, exocrine pancreatic function and intestinal inflammation on a 3 monthly basis after commencing treatment.MethodsStool samples pre- and 3 monthly post commencement of ivacaftor in 20 adult patients underwent metagenomic profiling of faecal microbiota. Faecal elastase-1 (FE-1), faecal calprotectin (FC) and faecal lactoferrin (FL) were measured using commercially available ELISA kits.ResultsIvacaftor did not significantly alter gut microbial diversity, as measured by chao1 (p = 0.886). At phylum, family and genus levels significant increases were observed in Bacteroidetes (p = 0.044), Bacteroidaceae (p = 0.021) and Bacteroides (p = 0.021). Significant decreases were observed in Microbacteriaceae (p = 0.003) and Eubacteriaceae (p = 0.014). A significant positive correlation was seen between FEV1 and gut microbiota diversity following treatment (r = 0.4, p = 0.002). No significant difference was measured in levels of FE-1 (p = 0.267), FC (p = 0.406) or FL (p = 0.779).ConclusionIvacaftor therapy has a normalisation effect on the gut microbiota, directing the microbiota towards a non-CF profile. Despite this elevated intestinal inflammation was sustained. Lack of exocrine pancreatic recovery may reflect established exocrine pancreatic dysfunction in an adult cohort. On-going longitudinal prospective data may demonstrate further improvements in the gut health of this cohort.

    AB - ObjectivesIvacaftor is effective in the treatment of patients with CF and the G551D gating mutation. We present faecal analysis results of the CORK cohort, a single-centre, adult (n = 20), prospective, longitudinal study of G551D clinical responders (median follow-up 12 months), examining the gut microbiota, exocrine pancreatic function and intestinal inflammation on a 3 monthly basis after commencing treatment.MethodsStool samples pre- and 3 monthly post commencement of ivacaftor in 20 adult patients underwent metagenomic profiling of faecal microbiota. Faecal elastase-1 (FE-1), faecal calprotectin (FC) and faecal lactoferrin (FL) were measured using commercially available ELISA kits.ResultsIvacaftor did not significantly alter gut microbial diversity, as measured by chao1 (p = 0.886). At phylum, family and genus levels significant increases were observed in Bacteroidetes (p = 0.044), Bacteroidaceae (p = 0.021) and Bacteroides (p = 0.021). Significant decreases were observed in Microbacteriaceae (p = 0.003) and Eubacteriaceae (p = 0.014). A significant positive correlation was seen between FEV1 and gut microbiota diversity following treatment (r = 0.4, p = 0.002). No significant difference was measured in levels of FE-1 (p = 0.267), FC (p = 0.406) or FL (p = 0.779).ConclusionIvacaftor therapy has a normalisation effect on the gut microbiota, directing the microbiota towards a non-CF profile. Despite this elevated intestinal inflammation was sustained. Lack of exocrine pancreatic recovery may reflect established exocrine pancreatic dysfunction in an adult cohort. On-going longitudinal prospective data may demonstrate further improvements in the gut health of this cohort.

    KW - Cystic Fibrosis

    KW - Gut microbiota

    KW - Ivacaftor

    U2 - 10.1016/S1569-1993

    DO - 10.1016/S1569-1993

    M3 - Article

    VL - 14

    SP - 29

    JO - Journal of Cystic Fibrosis

    T2 - Journal of Cystic Fibrosis

    JF - Journal of Cystic Fibrosis

    SN - 1569-1993

    IS - 1

    ER -