Predictive biomarkers and the role of the microbiome determining response to antiinflammatory treatment in Inflammatory Bowel Disease (Crohn's disease and ulcerative colitis)

Inflammatory bowel disease (IBD) is a term used to include several diseases,
most commonly Crohn*s disease (CD) and ulcerative colitis (UC), which are
chronic idiopathic diseases affecting the gastrointestinal tract. Given the
relapsing and unrelenting course of both conditions, a majority of patients
will experience disease progression and complications that ultimately lead to
significant symptoms affecting quality of life and increased disability,
morbidity and mortality as compared with the general population.
New treatments are needed and currently available treatments need further
investigation. So far, most scientific research has focused at potential
biomarkers in the genome and in the serum of patients with active disease,
however no strong predictors have been identified for any of the therapies.
Therefore, different biobank approaches are necessary in order to be able to
identify more sensitive markers predicting response.

In this project we will investigate biomarkers, cell types and microbiome in
biopsies collected from patients with IBD before treatment is started with
established therapeutic agents as well as during treatment. The interaction of
the microbiome will primarily be determined at the level of the mucosa-adherent
microbiome. In parallel, blood (DNA, RNA), serum and faeces will be stored to
identify how well the genotype (and related gene expression), serum biomarker
profile and faecal (luminal) microbiome and metabolome reflect the situation in
the mucosa.
After collection of the data, a system biology approach will be applied for
analysis. In the end, the goal is to identify patterns in the intestinal
pathophysiology (inflammatory cell types and mucosal microbiome) in patients
who response and fail to respond to different treatments. Finally, correlation
of the mucosal findings to measurements in serum, DNA and *luminal bacteria*
may allow the establishment of more easily applicable models for response to
treatments.

This is a study based on a systems biology approach. Individual IBD patients
with active disease will be studied before a new anti-inflammatory treatment is
started and during this treatment based on the standardized follow-up in
routine care. In parallel to the collection of patients* phenotypic data and
detailed information on response to various treatments, mucosal biopsies will
be collected and analysed for cytokines and chemokines, cell types and
mucosa-associated microbiome. Moreover, blood, serum and faeces will be stored
for analysis of the genotype, gene expression, the serum cytokine/chemokine
profile and the *luminal* faecal microbiome/metabolome. This observational
study is a multi-center study in the Academic Medical Center and OLVG oost in
Amsterdam for the coming 10 years. Therefore we want to enroll 2240 patients.

The potential risks are minimal in this study and are part of the routine care.
Peripheral blood is sampled with a negligible risk and low burden.
Endoscopy biopsies taken during sigmoido /colonoscopy include a minimal risk
(+/- 1:10000)