Maastricht IBS Cohort: Phenotypical and genotypical characterization of patients with Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is a functional intestinal disorder
characterized by abdominal pain or discomfort associated with altered bowel
habits, without indications for an organic cause. Complaints often increase
after a meal, especially if the meal is rich in fat, and are reduced by
defecation.

The etiology of IBS is not yet clear and a single causal factor cannot be
defined. Psychological and social factors, like anxiety and depression seem to
play a role. Furthermore biological factors like bacterial overgrowth, a
dysregulation of the brain-gut-axis (i.e. serotonin dysfunction), increase in
gut permeability, previous acute gastroenteritis, low grade inflammation and an
increase in the number of mast cells and T-lymphocytes in the gut mucosa have
been associated with IBS.

Several twin studies and familial aggregation studies in IBS are consistent
with either a genetic or social learning hypothesis, and it is possible that
both play a role. The prospect of identifying a genetic cause for IBS may be
very important, because it raises the possibility of confirming that IBS is a
disease entity and suggests new insight into the pathophysiology of the
disorder, providing new targets for drug development.

A promising test to positively diagnose IBS is the assessment of visceral
perception (rectal barostat). If such a test could support an anamnestic
assumption of IBS, this may limit more invasive investigations.

Aim of the present study is to set up a large cohort of IBS patients in order
to identify different disease characteristics as well as aetiological and
pathophysiological factors in (sub)groups of patients with this heterogeneous
disorder. Various phenotypical and genotypical markers will be evaluated. For
this purpose, blood and faecal samples as well as symptom questionnaires will
be collected and visceral perception and intestinal permeability will be
measured.
Therefore we will set up a biobank to collect human material for future studies
that will focus on the pathophysiology and disease characteristics of IBS,
especially biochemical, microbial and genetic factors. Consent will be asked to
collect data from standard questionnaires, to store serum samples, DNA, stool,
VOCs and, when endoscopy is performed for clinical reasons, also biopsy
specimens.

The tests are divided in baseline and optional part. The study participants
(IBS-patients and healthy volunteers) will be asked to participate in the
baseline part of the study and to be contactes for follow-up measurements after
3 and 5 years.
Those participating will be asked separately to participate in the optional
part of the study. If subjects are not willing to participate in the optional
part, they still can participate in the study.

Baseline analyses for inclusion in the study:
1. Questionnaires on symptoms, patient characteristics and dietary habits
2. Symptom diary, 14 days
3. Faecal collection
4. Collection of blood
5. Collection of exhaled air
6. Short mobility examination

Optional tests:
7. Gut permeability test (1 day of urine collection after ingestion of sugar
drink)
8. Rectal barostat
9. ESM (digitel questionnaires)

The following tests will be performed at home:
Gut permeability test (1 day), Symptom diary (2 weeks) and ESM (1 week).
The other test will be performed at the medical centre.

The following tests will be performed in case a colonoscopy, sigmoidoscopy, or
gastroduodenoscopy for clinical reasons is indicated and requested by the
physician of the IBS patient:
10. Collection of biopsies

11. Side Study: 30 patients will be asked to collect all facel samples during
one week, for microbiota analysis.

After 3 and 5 years, subjects will be invited to answer the questionnaires
digitally again and to provide a blood, fecal and exhaled air sample.

For the follow-up assessment 2020, subjects will be invited to answer some
digital questionnaires.

During blood sampling, the subjects will remain seated in a comfortable chair,
with an adjustable back. No side effects are expected when sampling blood in
this manner. Sometimes a bruise develops where the needle was inserted.

Barostat catheters used are commercially available and are safe for human use.
The protocol used in this study is a clinically used, widely accepted protocol
for testing visceral sensitivity and the same procedure was approved previously
by the Medical Ethical Committee Maastricht (MEC 06-3-020). Introduction of the
ballon can be uncomfortable. Inflation of the balloon can give discomfort, pain
or urgency. In case a subjec reports intolerable pain, discomfort or urgency,
the balloon will be deflated inmediately.

All ingredients of the gut permeability test beverage (lactulose, rhamnose and
sucralose) are used in the food industry and are generally regarded as safe. No
health risk is associated with the consumption of the test beverage and the
subsequent collection of 24-h urine. Furthermore, the application of
lactulose, rhamnose and sucralose, which will be used, has been approved
previously by the Ethics committee (MEC 04-168).

The complication rate of endoscopy (including mucosal biopsy) is very low:
0.13% bleeding and 0.03% perforation.

Completing symptom questionnaires will last for 60 minutes. The short mobility
examination will take up to 5 minutes.*