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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 and Plant, Barry J (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, 14 (1). p. 29. [Journal article]

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URL: http://www.sciencedirect.com/science/article/pii/S1569199315300904

DOI: https://doi.org/10.1016/S1569-1993(15)30090-4

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.

Item Type:Journal article
Keywords:Cystic Fibrosis, Gut microbiota, Ivacaftor
Faculties and Schools:Faculty of Life and Health Sciences > School of Biomedical Sciences
Faculty of Life and Health Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute > Genomic Medicine
Biomedical Sciences Research Institute
ID Code:39202
Deposited By: Dr Jennifer Deane
Deposited On:02 Jan 2018 14:51
Last Modified:02 Jan 2018 14:51

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