Yeop, Intan Faizura;
(2020)
The Gastrointestinal Microbiota and Immunity with Treatment in Paediatric Inflammatory Bowel Disease.
Doctoral thesis (Ph.D), UCL (University College London).
Preview |
Text
eThesis.pdf - Submitted Version Download (9MB) | Preview |
Abstract
Intestinal microbiota is strongly implicated in IBD pathogenesis. These microbes exert their influence directly and indirectly through their metabolites which include short chain fatty acids (SCFA). These interactions can be mutually beneficial but can also be detrimental to the host. Combined with a dysregulated immune system, IBD manifests itself in genetically susceptible individuals. These 3 interrelated factors, intestinal microbiota, SCFA and host immunity, were investigated to explore the extent of their associations. Intestinal luminal (stool and duodenal lavages) and mucosal biopsies were collected prospectively from treatment-naive IBD patients, some before diagnosis. Their clinical histories, results and dietetic assessment were also analysed. Dynamic changes in the intestinal microbial profiles with inflammation and treatment were compared to healthy and non-inflammatory control children. The corresponding alterations in stool SCFA, plasma cytokine and vascular profiles were identified. Dysbiosis was characterised at phyla level, and disease-specific microbial profiles in Crohn’s Disease (CD) and Ulcerative colitis (UC) were recorded. The relative abundances of the 3 main phyla (Bacteroidetes, Firmicutes and Proteobacteria) varied with disease activity. Proteobacteria abundance increased with inflammation. Distinct differences in SCFA profiles were observed between control groups and IBD, with distinguishing features evident between CD, UC and ileostomy samples. Inflammation appears to influence SCFA production, particularly butyrate. In addition, pro-inflammatory cytokines and vascular markers mirrored trends in clinical inflammatory markers, and some correlated with SCFA percentages. In conclusion, alterations in intestinal microbial and SCFA profiles appear to influence the systemic cytokine milieu. Larger cohort studies are needed to confirm and further explore these findings if we are to utilise microbial and immune profiles in our quest for personalised treatment of children with IBD.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | The Gastrointestinal Microbiota and Immunity with Treatment in Paediatric Inflammatory Bowel Disease |
| Event: | UCL (University College London) |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2019. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10088162 |
Archive Staff Only
 |
View Item |
