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


    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.
    Original languageEnglish
    Pages (from-to)29
    JournalJournal of Cystic Fibrosis
    Issue number1
    Publication statusAccepted/In press - 20 Jun 2015



    • Cystic Fibrosis
    • Gut microbiota
    • Ivacaftor

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