MESENCROHN: Mesenteric Bacterial Translocation in Evolved Crohn's Disease
Study Details
Study Description
Brief Summary
Mesenteric fat can be invaded by gut bacteria through a process called bacterial translocation, which is the invasion of viable bacteria from the gastrointestinal tract to extraintestinal sites (mesenteric lymph nodes, liver, spleen, kidney, bloodstream, etc.). In Crohn's disease (CD), bacterial translocation could increase the disproportionate inflammatory response already present and contribute to disease progression by stimulating the production of pro-inflammatory cytokines and immune-cell infiltration in the mesentery. Several mechanisms may promote bacterial translocation, such as bacterial overgrowth, disruption of the intestinal mucosal barrier and alterations in the immune system.
Ileocecal surgical resection is required in some patients with complicated or refractory CD. Unfortunately, post-surgical disease recurrence happens in up to 40% of cases, probably defining a subgroup of CD patients with a particular aggressive form of the disease. The complete microbiome (in gastrointestinal and extraintestinal sites) in CD patients that develop early post-surgical recurrence, as well as the association to innate immunity alterations, has not yet been studied.
The primary aim of the study is to explore the bacterial microbiome of CD patients and its association with early post-surgical recurrence and clinical or genetic variables related to innate immunity. To achieve this, the bacterial DNA present in mesenteric fat and ileal tissue (inflamed and non-inflamed) from surgical resection samples as well as blood samples from CD patients will be studied. Genetic polymorphisms, relevant clinical data and disease recurrence will also be evaluated.
The investigators hypothesize that bacterial translocation to the mesentery fat near the inflamed intestine is one of the mechanisms for perpetuation and chronicity of inflammation and therefore post-surgical recurrence in CD. The investigators expect to find a distinctive bacterial profile (in quantity and quality) in the mesenteric fat of patients with early post-surgical recurrence and/or with genetic variants that cause alterations in innate immunity.
The study of the microbiome in CD could help to identify the patients with a more aggressive disease form that will probably present early post-surgical recurrence, and could raise the possibility of microbial modulation as therapy for CD.
Condition or Disease | Intervention/Treatment | Phase |
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Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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CD patients requiring surgical treatment (ileocecal resection)
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Control group Patients requiring an ileocecal resection for a cause other than CD |
Outcome Measures
Primary Outcome Measures
- Predictive power of the bacterial microbiome profile over early post-surgical disease recurrence in CD patients [at inclusion (surgery) + additional study of bacterial DNA in blood at 3 months in CD patients)]
Characterization of the microbiota present in the mesentery, ileal tissue and blood.
Secondary Outcome Measures
- Association analysis of genetic variants related to innate immunity and the bacterial microbiome profile of CD patients [at inclusion (surgery)]
DNA polymorphisms detection in blood: ATG16L1 (rs2241880, rs3792109, rs3828309); NOD2 / CARD15 (rs2066844, rs2066845) and IRGM (rs13361189, rs4958847, rs1336119, rs10065172, rs7714584).
Eligibility Criteria
Criteria
Inclusion Criteria:
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Adults (18 years or older)
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Informed consent signed
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To require an ileocecal resection as part of the treatment of Crohn's Disease
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In the case of controls: not having Inflammatory Bowel Disease and requiring an ileocecal resection for another reason
Exclusion Criteria:
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To require an ileocecal resection with definitive or transient ileostomy
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In the case of controls: existence of a family history of Inflammatory Bowel Disease.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Hospital Universitari MĂștuaTerrassa | Terrassa | Barcelona | Spain | 08221 |
Sponsors and Collaborators
- Hospital Mutua de Terrassa
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
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- MESENCROHN