Mesenteric Bacterial Translocation in Evolved Crohn's Disease

Study Overview
=================
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.

Official Title
-----------------
Mesenteric Bacterial Translocation in Evolved Crohn's Disease

Conditions
-----------------
Crohn Disease

Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adults (18 years or older) Informed consent signed To require an ileocecal resection as part of the treatment of Crohn's Disease In the case of controls: not having Inflammatory Bowel Disease and requiring an ileocecal resection for another reason Exclusion Criteria: To require an ileocecal resection with definitive or transient ileostomy In the case of controls: existence of a family history of Inflammatory Bowel Disease.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| CD patients requiring surgical treatment (ileocecal resection)<br> | |
| Control group<br>Patients requiring an ileocecal resection for a cause other than CD | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in the proportions and abundance of bacterial taxa (defined as total percentage of bacterial DNA sequences) between the mesentery, ileal tissue and blood between CD patients with and without early post-surgical disease recurrence |  | at inclusion (surgery) | 
| Differences in the function of the bacterial profile (defined as the metagenome function analysis) between the mesentery, ileal tissue and blood between CD patients with and without early post-surgical disease recurrence |  | at inclusion (surgery) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Association analysis of genetic variants related to innate immunity and the bacterial microbiome profile of CD patients | DNA polymorphisms detection in blood: ATG16L1 (rs2241880, rs3792109, rs3828309); NOD2 / CARD15 (rs2066844, rs2066845) and IRGM (rs13361189, rs4958847, rs1336119, rs10065172, rs7714584). | at inclusion (surgery) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Crohn Disease, Mesenteric fat, Bacterial translocation, Innate immunity, Genetic polymorphisms