Cystic fibrosis and the gut microbiota

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dc.contributor.advisor Ross, R. Paul en
dc.contributor.advisor Stanton, Catherine en
dc.contributor.advisor Plant, Barry en
dc.contributor.advisor Rea, Mary en Deane, Jennifer 2018-06-21T09:15:58Z 2017 2017
dc.identifier.citation Deane, J. 2017. Cystic fibrosis and the gut microbiota. PhD Thesis, University College Cork. en
dc.identifier.endpage 288 en
dc.description.abstract The role of the gut microbiota in host health has been established in recent years and has been shown to be altered in numerous disease states, including Cystic Fibrosis (CF) cohorts. This thesis investigates the gut microbiota and microbiome in CF persons and how it may be manipulated through interventions with the potential to improve respiratory symptoms in CF persons. Firstly, in order to survey the CF gut microbiota composition, we performed a multicentre analysis of the prevalence of C. difficile in a CF cohort in three European sites (Ireland, UK and Belgium), reporting the highest carriage rate to date of 63-71% compared to 7% in age-matched healthy controls. C. difficile ribotypes were geographically distinct among the three sites, with a core of two ribotypes (046 and 078) shared among all sites. In order to identify probiotic species which would have potential to modulate the CF gut microbiota with respiratory benefits, we screened a biobank of lactobacilli and bifidobacterial isolates sourced from the CF gut microbiota for a putative probiotic with antibiotic tolerance, resulting in identification of L. plantarum 9_S2. In addition, the gut microbiota composition and function were examined following treatment with Cystic Fibrosis transmembrane conductance regulator (CFTR) modulation therapy, Ivacaftor. Despite clinical trials reporting improvements in lung function and reductions in pulmonary exacerbations, the effects on the gut microbiota composition, function and metabolome were subtle. Pancreatic function was not restored and intestinal inflammation was not reduced following commencement of Ivacaftor treatment. Finally, in order to overcome logistical issues of collecting sufficient amounts of fresh faecal samples on one day to perform distal colon models of the CF gut we investigated the viability of freezing faecal samples prior to preparation of faecal inoculum. Overall the results presented in this thesis demonstrate the differences in the gut microbiota between CF persons and healthy cohorts and demonstrate that interventions may result in subtle normalisations of the CF gut microbiota. en
dc.description.sponsorship CFMATTERS is a Collaboration Project funded by the European Union under the 7th Framework Programme under grant agreement n° 603038. en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher University College Cork en
dc.rights © 2017, Jennifer Deane. en
dc.rights.uri en
dc.subject Cystic fibrosis en
dc.subject Gut microbiota en
dc.title Cystic fibrosis and the gut microbiota en
dc.type Doctoral thesis en
dc.type.qualificationlevel Doctoral en
dc.type.qualificationname PhD en
dc.internal.availability Full text not available en Restricted to everyone for five years en 2023-06-20T09:15:58Z
dc.description.version Accepted Version
dc.contributor.funder Seventh Framework Programme en
dc.description.status Not peer reviewed en Medicine en Microbiology en
dc.check.reason This thesis is due for publication or the author is actively seeking to publish this material en
dc.check.opt-out Not applicable en
dc.thesis.opt-out false
dc.check.entireThesis Entire Thesis Restricted
dc.check.embargoformat Apply the embargo to both hard bound copy and e-thesis (If you have submitted an e-thesis and a hard bound thesis and want to embargo both) en
dc.internal.conferring Spring 2018 en

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© 2017, Jennifer Deane. Except where otherwise noted, this item's license is described as © 2017, Jennifer Deane.
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