Influence of Mechanical Bowel Preparation on GI Microbiota
Influence of Mechanical Bowel Preparation on GI Microbiota
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).
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.

 Hypothesis: Bowel preparation for endoscopy will destabilise the gut microbiota in patients
 with diverticulosis. Re-establishment of this microbiota follows an altered developmental
 trajectory resulting in sustained changes to the composition of the microbiota. Furthermore,
 these observed changes will have functional consequences as identified through altered
 metabolic interactions at the microbe-host interface.

 Aims and objectives:

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

 2. Functional consequences of such changes to host metabolism, host-microbe co-metabolism
 and short chain fatty acid production will be assessed (nuclear magnetic resonance
 spectroscopy and gas chromatography respectively).

 3. Statistical data integration techniques will identify links between the altered
 microbiota and metabolic profiles to begin to determine the mechanisms underlying the
 influence of the gut microbiota in diverticulosis .

 4. The outputs above will identify whether a 'window of opportunity' occurs following BP
 which could be exploited to rectify dysbiosis as a basis for a later larger-scale study.

 Experimental design

 In order to assess the effects of BP on the colonic microbiota in diverticulosis,
 post-menopausal women with mild non-specific left sided abdominal pain and diarrhoea, who
 have been referred to the colorectal unit at the Royal Berkshire Hospital , will be recruited
 by the applicants (KT, PC). Patients who have not received antibiotics in the previous 3
 months will complete a questionnaire to assess gastrointestinal symptoms, which will be based
 on those used in our previous human Irritable Bowel Syndrome (IBS) trials. Urine will be
 collected at t=0 (before BP), t=2d (24h after BP), t=8d (1 week after BP) and t=3 months
 (when recalled to the hospital). Faeces will be collected at the same timepoints except t=2d,
 instead the first void following BP will be requested. Patients are sent oral BP by post or
 collect them from the endoscopy unit, and we will exploit this to deliver faecal sample pots.
 Samples will be provided either at the hospital and immediately frozen, or patients will be
 asked to freeze and bring with them to their appointment . Later samples (t-8d, t=3 months),
 will be kept frozen at home then collected by University of Reading staff once both samples
 have been collected. Upon collection, patients will be provided with the questionnaire (and
 self-addressed envelope) to allow comparison of their symptoms 2 weeks and 3 months post BP
 with those reported beforehand (t=0).
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