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Title: Optimising the medical management of ileoanal pouch related complications and discovering novel therapeutic avenues through metabonomic profiling
Author: Segal, Jonathan Philip
ISNI:       0000 0004 8511 0873
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2019
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Restorative proctocolectomy is considered a quality of life surgical procedure in patients with ulcerative colitis who fail to respond to conventional medical therapies and in some patients with Familial Adenomatous Polyposis. This thesis explores the current management of chronic primary idiopathic pouchitis through a systematic review and meta-analysis. Following this review I have explored the clinical utility of antibiotics and biologics in a cohort of patients with both chronic primary idiopathic pouchitis and pre-pouch ileitis. I have found that the treatment options for chronic pouchitis and pre-pouch ileitis are limited and that long-term treatments such as antibiotics and biologics are ineffective in a significant proportion of patients often leading to a permanent ileostomy. I have also explored the effect of some non-medical therapies including biofeedback and the Renew® anal insert for incontinence and evacuatory problems and have shown that they may be a useful adjunct in the treatment of these pouch related complications. The second focus of the thesis is to try and understand the mechanisms that drive the development of pouchitis. I undertook a systematic review to explore what was already known about the gut microbiota and its role in health and disease of the pouch. I then utilised next generation sequencing technologies to include metataxonomics, nuclear magnetic resonance and mass-spectrometry gas chromatography to link the gut microbiota with the metabolic signatures in serum, urine, faeces and mucosal tissue. I used these techniques to compare patients with pouchitis against healthy controls and patients with Familial Adenomatous Polyposis. These studies have highlighted the importance of the Firmicutes phylum and their role in the production of short chain fatty acids. I have found that a depletion in short chain fatty acids may contribute to the development of pouchitis. Future work may build on methods to increase short chain fatty acid delivery to the pouch through methods such as dietary interventions, distal feeding prior to continuity surgery or direct short chain fatty acid supplementation delivered topically to the pouch.
Supervisor: Hart, Ailsa ; Clark, Sue ; Marchesi, Julian Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral