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Clinical Trials/NCT03465293
NCT03465293UnknownNot Applicable

Does Mechanical Bowel Preparation Destabilise the Gut Microbiota and Provide a Window of Opportunity in Which to Influence the Re-establishing Microbiota in Diverticulosis?

University of Reading0 sites15 target enrollmentStarted: May 1, 2018Last updated:
Conditions

Trial Snapshot

Phase
Not Applicable
Enrollment
15
Primary Endpoint
Composition of the colonic microbiota pre and post bowel preparation

Study Overview

Brief Summary

The mechanical bowel preparation (BP) used to clean the colon prior to colonoscopy frequently results in a significant but temporary reduction in patient's symptoms for a number of bowel disorders including symptomatic uncomplicated diverticular disease. The cause of this improvement is unknown.

We hypothesise that changes to the gut microbial population (microbiota) are responsible for this improvement and that the repopulation of the GI tract with bacteria following colonoscopy results in a return of their normal symptoms. This pilot study will test this in a preliminary way by examining the stool, urine and blood of patients before and after bowel preparation to detect any destabilising effect that BP has on the gut microbiota and to what extent the microbiota repopulates at 3 months If the hypothesis is proven, this study will show that BP generates a 'window of opportunity' in which to influence the subsequent re-establishment of the microbiota. This is with the eventual aim of correcting potential dysbiosis and preventing the progression of symptomatic uncomplicated diverticular disease (SUDD).

Detailed Description

The mechanical bowel preparation (BP) procedure, which directly precedes colonic endoscopy, results in a significant reduction in reported symptoms for several bowel disorders (eg irritable bowel syndrome (IBS )), but as yet, there is little research-based supporting evidence. This proposal will use a robust experimental design to explore both the composition of the microbiota, and importantly, its metabolic activity to assess interactions with human hosts following BP. The aim of this pilot study is to generate data demonstrating the destabilising effects of BP on both the composition and metabolic activity of the gut microbiota.

If the hypothesis is proven, this study will show that BP generates a 'window of opportunity' in which to influence the subsequent re-establishment of the microbiota. This is with the eventual aim of correcting dysbiosis and preventing the development of symptomatic uncomplicated diverticular disease in patients with diverticulosis.

Background Diverticular disease, characterised by weakness of the supporting connective tissue of the wall of the colon leading to the formation of diverticula1, is somewhat neglected and does not receive scientific attention that other inflammatory gut disorders have. Despite this condition affecting 50% of our aging population, approximately 1/5 of which will develop debilitating symptomatic uncomplicated diverticular disease (SUDD)2, there is a paucity of knowledge in this field.

The factors determining the transition from asymptomatic diverticulosis to SUDD are unclear. However, the gut microbiota has been implicated in a recent small-scale study which correlated diverticulosis with depletion of Clostridium cluster IV. Clostridium cluster IX, Fusobacterium and Lactobacillaceae, all of which can exert an anti-inflammatory effects. Patients who present with left-side non-specific abdominal pain and diarrhoea are assessed by colonic endoscopy. A small-scale study showed that this procedure also resulted in a significant reduction in Lactobacillaceae in the control population after 1 month (n=10).

BP is received 14 and 20 hours prior to colonoscopy and involves oral administration with a variety of stimulant laxatives (eg Moviprep - polyethylene glycol) resulting in severe diarrhoea and complete clearance of faecal matter from the bowel. It is likely that this BP is implicated in any reduction in reported symptoms as opposed to the endoscopic procedure itself, although putative underlying mechanisms have yet to be identified.

Study Design

Study Type
Observational
Observational Model
Cohort
Time Perspective
Prospective

Eligibility Criteria

Ages
18 Years to 80 Years (Adult, Older Adult)
Sex
Female
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Suspected symptomatic uncomplicated diverticular disease
  • Requires colonoscopy for investigation of symptoms

Exclusion Criteria

  • Under 18yo
  • Previous bowel resection
  • Antibiotics use in the last 6 months
  • Medical condition precluding colonoscopy

Outcomes

Primary Outcomes

Composition of the colonic microbiota pre and post bowel preparation

Time Frame: 6 months

Quantify sustained observational changes which occur within the functional groups of the gut microbiota following BP (HTP FISHflow technology)

Activity of the microbiota pre and post bowel preparation

Time Frame: 6 months

Functional consequences of observed changes to host metabolism, host-microbe co-metabolism and short chain fatty acid production. This will be assessed by NMR spectroscopy and gas chromatography respectively

Secondary Outcomes

No secondary outcomes reported

Investigators

Sponsor Class
Other
Responsible Party
Principal Investigator
Principal Investigator

Marie Lewis

Dr

University of Reading

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