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Title: Studies of the aetiopathogenesis of pouchitis
Author: Landy, Jonathan
ISNI:       0000 0004 7233 0279
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2015
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The ileal pouch offers a unique opportunity to study the inter-relationships between the gut microbiota, barrier function and host immune responses. Intestinal dendritic cells (DC) are pivotal in the maintenance of gut immune homeostasis. Impaired barrier function due to altered cell to cell junctions, enables interactions between the microbiota and host immune responses prior to the onset of inflammation and epithelial damage. The role of innate immune factors in pouchitis remains unclear. We performed cross sectional and longitudinal studies of patients following restorative proctocolectomy and assessed DC and tight junction protein (TJP) characteristics in the ileal pouch. Increased expression of the “pore-forming” claudin 2 was an early event in the development of pouch inflammation and aberrant DC expression of gut homing markers was characterised in the ileum and ileal pouch of ulcerative colitis patients without inflammation. DC phenotype in pouchitis suggested an activated innate immune response to microbial signals. Intestinal immune responses may be manipulated by modification of the gut microbiota. An emerging approach is transplantation of the entire “organ” of the gut microbiota. Effects of faecal microbiota transplantation (FMT) on recipient microbiota and immune responses in inflammatory bowel diseases are unknown. A single nasogastrically delivered FMT from a healthy donor to patients with chronic pouchitis, resulted in some shift in the composition of the microbiota, with specific changes in the abundance of species suggestive of a “healthier” pouch microbiota. However, microbiota engraftment success varied greatly between recipients and regardless of engraftment success, FMT did not result in immunological response or clinical efficacy. In conclusion, aberrant DC and TJP characteristics are associated with inflammation of the ileal pouch. Manipulation of the microbiota by FMT may be one means of modifying DC and TJP expression in the ileal pouch. However, these factors were not influenced by a single nasogastrically delivered FMT.
Supervisor: Knight, Stella ; Clark, Sue Sponsor: Eli and Edythe Broad Foundation
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral