The aim of our project is in-depth characterization of the microbiota components both adjacent to and within the mucosa in patients with IBD, by applying novel high-throughput analysis technology in a global description strategy approach.…
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Nature and transmural spatial distribution of the enteric microbiota in IBD
patients.
- Changes in mucosal microbiota of the sigmoid in IBD after diverting ostomy.
- Phenotype and characterise the immune cells involved in IBD.
Secondary outcome
- Presence of microbial DNA in granuloma*s of CD patients.
- Assessment of co-localisation and signalling between invading microbes,
lamina propria macrophages dendritic cells and adaptive and innate immune cells.
- Alterations of phagosome maturation and autophagy, as well as apoptosis of
mucosal macrophages and dendritic cells in IBD.
Background summary
Inflammatory bowel disease (IBD) consists of Crohn*s disease (CD) and
ulcerative colitis (UC). Patients suffer from chronic intestinal inflammation
leading to bloody diarrhea, weight loss and fatigue. The current prevailing
hypothesis states that the pathogenesis involves an inappropriate and ongoing
activation of the mucosal immune system driven by the intestinal microbiota in
a genetically predisposed individual. However, it is not known which
constituents of the microbiota and which components of the innate and adaptive
immune response are involved. The human microbiota forms a highly complex
ecosystem with its host and may comprise more than 1800 phylotypes. We
hypothesize that the perturbed interplay between certain constituents of the
microbiota and the host is caused by invading organisms, which after crossing
the epithelial barrier, are capable of initiating and/or persisting an
activated immune response. The clearing of certain microbiota might be impaired
by dysfunctioning of the intestinal housekeeping cells. This dysfunction may be
due to either interaction of invading microorganisms with these housekeeping
cells, or, alternatively, by inhibitory signalling of these cells by other
immune cells The delicate balance between pro- and anti-inflammatory cells in
the intestinal lamina propria is therefore disturbed and this may result in
IBD. Different types of immune cells produce cytokines involved in inflammation
in the intestine, including both adaptive and innate immune cells. When the
role and interaction of microbiota and immune cells is elucidated, new
therapeutic strategies can be investigated for improvement of the care for IBD
patients.
Study objective
The aim of our project is in-depth characterization of the microbiota
components both adjacent to and within the mucosa in patients with IBD, by
applying novel high-throughput analysis technology in a global description
strategy approach. Furthermore, we aim to assess the interaction between
invading microorganisms, local housekeeping cells and the adaptive and innate
immune system in the intestine.
Study design
This is an exploratory global description approach with a subsequent
hypothesis-driven part.
Study burden and risks
Since this is an exploratory global description study there is no risk of
participation in this study for most of the patients. Blood is obtained during
routine laboratory control, with a negligible risk of haematoma.
In patients who are scheduled for ostomy a minimal risk of perforation or
bleeding exists due to endoscopy.
Only resection material which is not used for routine histology of the specimen
is investigated, thus no diagnostic procedures are hampered by this study.
There is no direct potential benefit for patients participating in this
protocol. However, this project may generate important data regarding the
disturbed interplay of the microbiota with the innate immunity in IBD, which
will increase our understanding of this chronic debilitating conditions and may
lead to designing new therapeutic strategies.
Postbus 22600
1100 DD Amsterdam
NL
Postbus 22600
1100 DD Amsterdam
NL
Listed location countries
Age
Inclusion criteria
*18 year old male or female, able to give informed consent
Established Crohn*s disease or ulcerative colitis (according to the Lennard-Jones criteria), or patients scheduled for diverting ostomy due to IBD.
control patients: patients who undergo intestinal resection due to a gastrointestinal malignancy
Exclusion criteria
Ischemia of the bowel
Positive stool cultures or parasite tests for common enteric pathogens (with exeption of non pathogenic parasites such as Blastocystis hominis or Endolimax nana)
Use of Antiobiotics in preceding 4 weeks
use of probiotics in preceding 8 weeks
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL34133.018.10 |