Towards a translational understanding of colonic bacteria in Crohn's disease pathology

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O'Donoghue, Keith
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University College Cork
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Crohn’s disease (CD) is a chronic inflammatory condition of unknown aetiology, with the microbiota thought to be a major contributor to the disease. This thesis aimed to investigate the potential role of the gut microbiota in this context. The approaches taken were to examine CD associated Bacteroides. We choose 3 Bacteroides species (B. fragilis, B. vulgatus, B. thetaiotaomicron) to examine here, for their ability to impact gut related functions via a range approach from cell culture to metabolite production and in application to relevant animal models. We found subtle, but significant effects in co-cultures with cells via supernatants that could induce changes to gene expression to impact cell proliferation and maturation as well as immune response modulation. The effects were strain dependent, and they were impactful. The work revealed alterations to signalling metabolites, bile acids, again in a strain dependant manner. These effects did not translate to huge changes in metabolites in vivo, in normal mice and in the genetic CD model. However, gender specific changes to inflammation modulation, BAs, the faecal microbiota and in signalling were determined in female mice related to the antibiotic cocktail issued to them and altered in male mice colonized by B. vulgatus. The work provides several different impacts towards future direction, this work has also been, in part, published.
Crohn's disease , Microbiome , Bacteroides , Epithelium , Bile acids
O'Donoghue, K. W. 2022. Towards a translational understanding of colonic bacteria in Crohn's disease pathology. PhD Thesis, University College Cork.