Cystic fibrosis and the gut microbiota

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.

Grantor dc:publisher

University College Cork

Year dc:date.issued

2017

Author dc:creator

• Deane, Jennifer

Advisors dc:contributor.advisor

• Ross, R. Paul
• Stanton, Catherine
• Plant, Barry
• Rea, Mary

• Cystic fibrosis
• Gut microbiota

Statement dc:rights

• © 2017, Jennifer Deane.

Licence dc:rights.uri

• http://creativecommons.org/licenses/by-nc-nd/3.0/

Language dc:language.iso

en

Handle dc:identifier.uri

https://hdl.handle.net/10468/6374

OAI identifier oai:identifier

oai:cora.ucc.ie:10468/6374