The impact of a defunctioning ileostomy on bowel mucosal homeostasis, and a novel intervention for pre-habilitation of the microbiome
File(s)
Author(s)
Dilke, Stella
Type
Thesis
Abstract
Distal feeding (DF) is a relatively novel method of enteral feeding which has been utilised worldwide in the treatment of intestinal failure. It involves intubation of the distal limb of a stoma, into a defunctioned section of bowel, and trophically feeding with either a prebiotic mixture or with the patient’s own small bowel effluent (chyme). DF has been examined as a treatment for patients following low anterior resection or total mesorectal excision for colorectal cancer (CRC) in a very limited way previously. These patients are at high risk of immediate post-operative complications including ileus and anastomotic leak, and longer-term complications have already been linked with the formation of an ileostomy.
This body of work interrogates the clinical impact and quality of life, and the microbial, metabolic and immunological changes that occur in patients with a defunctioned bowel, as well as at serial time points during a DF regimen.
Experimental results from this thesis demonstrate that the microbial composition of ileal and colonic bacteria are directly influenced by the systemic immune response and that the longstanding impact of both CRC and a defunctioning stoma are significant, even when the underlying pathology has been conclusively treated.
DF changes the functional gene abundance of colonic bacterial communities, their systemic immune response and metabolic by-products, and subsequently reduces immediate post-operative complications improving patient quality of life. A DF regimen using chyme produced more significant and wide-ranging results across the experiment subtypes but was less acceptable to patients. Patients who had undergone chemotherapy for CRC had distinct microbial, immunological and metabolic signatures.
Clinical outcomes such as length of hospital stay, cost of inpatient stay and return to intestinal autonomy were investigated, alongside in-depth qualitative research into the impact of ileostomy and feasibility of DF.
This body of work interrogates the clinical impact and quality of life, and the microbial, metabolic and immunological changes that occur in patients with a defunctioned bowel, as well as at serial time points during a DF regimen.
Experimental results from this thesis demonstrate that the microbial composition of ileal and colonic bacteria are directly influenced by the systemic immune response and that the longstanding impact of both CRC and a defunctioning stoma are significant, even when the underlying pathology has been conclusively treated.
DF changes the functional gene abundance of colonic bacterial communities, their systemic immune response and metabolic by-products, and subsequently reduces immediate post-operative complications improving patient quality of life. A DF regimen using chyme produced more significant and wide-ranging results across the experiment subtypes but was less acceptable to patients. Patients who had undergone chemotherapy for CRC had distinct microbial, immunological and metabolic signatures.
Clinical outcomes such as length of hospital stay, cost of inpatient stay and return to intestinal autonomy were investigated, alongside in-depth qualitative research into the impact of ileostomy and feasibility of DF.
Version
Open Access
Date Issued
2022-03
Date Awarded
2023-07
Copyright Statement
Creative Commons Attribution NoDerivatives Licence
License URL
Advisor
Vaizey, Carolynne
Hanna, George
Wilson, Ana
Tozer, Philip
Hoyles, Lesley
Sponsor
Bowel Research UK
Publisher Department
Department of Surgery & Cancer
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)