The Bacterial Secretome in IBD

Study Overview
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Brief Summary
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Secreted bacterial effectors produced by the intestinal microbiota are in part responsible for the proinflammatory effect of the fecal content in inflammatory bowel disease (IBD) patients.

Detailed Description
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Fecal colonic content will be collected by suction during routine colonoscopy. From the fecal content different fractions (containing soluble bacterial fractions and membrane bound bacterial fractions) will be processed. These bacterial fractions (also termed as bacterial secretome) will be tested for proinflammatory potential in tissue culture assays including epithelial colonic cell lines and dendritic/monocytic cell lines. The main outcome parameter will be the secretion of proinflammatory cytokines from the tissue culture. For this purpose the investigators will test different groups of patients including patients with active/inactive Crohn's disease or ulcerative colitis, patients with other inflammatory conditions of the colon, patients with colorectal carcinoma and healthy controls undergoing colonoscopy.

Official Title
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The Bacterial Secretome in Crohn's Disease and Ulcerative Colitis

Conditions
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Inflammatory Bowel Diseases

Intervention / Treatment
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* Other: Colonic fluid collection during endoscopy for analysis of the bacterial secretome


Participation Criteria
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Eligibility Criteria
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Group 1 (healthy controls): n=20 Inclusion criteria: Colonoscopy performed for the following indications: anemia, blood in stool, constipation, change in bowel habits, screening for colon cancer, follow up after polyps, weight loss Macroscopic normal colonoscopy except for diverticulosis (without any signs of inflammation), ≤ 3 polyps (except hyperplastic polyps of the colon and rectum), angiodysplasia Exclusion criteria: Diagnosis of IBD or any other inflammatory condition of the small and large intestine Diagnosis of IBS Autoimmune disorders Obesity (BMI> 30) Regular intake of NSAIDs (> 2 tablets/ week), immunosuppressants Intake of antibiotics within the last 3 months Intestinal infection by enteric pathogens Probiotic therapy Group 2 (Crohn´s disease; CD): n= 20 (10 active CD; 10 inactive CD) Inclusion criteria: Colonoscopy indicated by routine clinical care Established diagnosis of Crohn´s disease (also if established by the study colonoscopy) Exclusion criteria: • Intestinal infection by enteric pathogens Definition of active CD Harvey-Bradshaw Index - HBI ≥ 5 and / or Simple Endoscopic Score for Crohn Disease (SES-CD) ≥ 3 Except SES-CD scores resulting from isolated lesions only located at the ileocolonic anastomosis consistent with a modified Rutgeerts score i2a (these patients are considered as endoscopically non active) Definition of inactive CD Harvey-Bradshaw Index (HBI) < 5 and Simple Endoscopic Score for Crohn Disease (SES-CD) < 3 Except SES-CD scores resulting from isolated lesions only located at the ileocolonic anastomosis consistent with a modified Rutgeerts score i2a (these patients are considered as endoscopically non active) Group 3 (Ulcerative colitis, UC): n= 20 (10 active UC; 10 inactive UC) Inclusion criteria: Colonoscopy indicated by routine clinical care Established diagnosis of ulcerative colitis (also if established by the study colonoscopy) Exclusion criteria: • Intestinal infection by enteric pathogens Definition of active UC Total Mayo score ≥ 3 and Endoscopic Mayo subscore ≥ 2 Definition of inactive UC Total Mayo score < 3 and Endoscopic Mayo subscore 0 or 1. Group 4 (Colorectal cancer): n= 10 Inclusion criteria: • Diagnosis of a lesion with suspicion for colorectal cancer during endoscopy which is confirmed later by histology Exclusion criteria: • None Group 5 (Colitis/Enteritis of different origin): n= 20 Inclusion criteria: Diagnosis of intestinal inflammation at endoscopy or histology E.g.: Infectious colitis /enteritis; ischemic Colitis; microscopic colitis; GVHD; NSAID colitis; Colitis of unknown cause Exclusion criteria: • None

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Healthy Controls<br>Inclusion criteria: Colonoscopy performed for the following indications: anemia, blood in stool, constipation, change in bowel habits, screening for colon cancer, follow up after polyps, weight loss Macroscopic normal colonoscopy except for diverticulosis (without any signs of inflammation), ≤ 3 polyps (except hyperplastic polyps of the colon and rectum), angiodysplasia Exclusion criteria: Diagnosis of IBD or any other inflammatory condition of the small and large intestine Diagnosis of irritable bowel syndrome (IBS) Autoimmune disorders Obesity (BMI> 30) Regular intake of NSAIDs (> 2 tablets/ week), immunosuppressants Intake of antibiotics within the last 3 months Intestinal infection by enteric pathogens Probiotic therapy | Other: Colonic fluid collection during endoscopy for analysis of the bacterial secretome<br>* Colonic content will be collected by suction during routine colonoscopy including the residual fluid in the colon and stool contents and also suction of washing fluid (sterile physiologic H2O solution)<br>|
| Active Comparator: Crohn's disease<br>2 Subgroups: inactive disease (10 patients) and active disease (10 patients) Inclusion criteria: Colonoscopy indicated by routine clinical care Established diagnosis of Crohn´s disease (also if established by the study colonoscopy) Exclusion criteria: • Intestinal infection by enteric pathogens | Other: Colonic fluid collection during endoscopy for analysis of the bacterial secretome<br>* Colonic content will be collected by suction during routine colonoscopy including the residual fluid in the colon and stool contents and also suction of washing fluid (sterile physiologic H2O solution)<br>|
| Active Comparator: Ulcerative Colitis<br>2 Subgroups: inactive disease (10 patients) and active disease (10 patients) Inclusion criteria: Colonoscopy indicated by routine clinical care Established diagnosis of ulcerative colitis (also if established by the study colonoscopy) Exclusion criteria: • Intestinal infection by enteric pathogens | Other: Colonic fluid collection during endoscopy for analysis of the bacterial secretome<br>* Colonic content will be collected by suction during routine colonoscopy including the residual fluid in the colon and stool contents and also suction of washing fluid (sterile physiologic H2O solution)<br>|
| Active Comparator: Colorectal carcinoma<br>Inclusion criteria: • Diagnosis of a lesion with suspicion for colorectal cancer during endoscopy which is confirmed later by histology Exclusion criteria: • None | Other: Colonic fluid collection during endoscopy for analysis of the bacterial secretome<br>* Colonic content will be collected by suction during routine colonoscopy including the residual fluid in the colon and stool contents and also suction of washing fluid (sterile physiologic H2O solution)<br>|
| Active Comparator: Colitis/Enteritis of other origin<br>Inclusion criteria: Diagnosis of intestinal inflammation at endoscopy or histology E.g.: Infectious colitis /enteritis; ischemic Colitis; microscopic colitis; graft versus host disease (GVHD); NSAID colitis; Colitis of unknown cause Exclusion criteria: • None | Other: Colonic fluid collection during endoscopy for analysis of the bacterial secretome<br>* Colonic content will be collected by suction during routine colonoscopy including the residual fluid in the colon and stool contents and also suction of washing fluid (sterile physiologic H2O solution)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of proinflammatory cytokines of bacterial fractions in IBD compared to healthy controls | Measurement of proinflammatory cytokines (f.e.: IL-8) in epithelial and dendritic tissue culture assays | One day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of proinflammatory cytokines of bacterial fractions in relation to disease activity | Measurement of proinflammatory cytokines (f.e.: IL-8) in epithelial and dendritic tissue culture assays | One day | 
| Concentration of proinflammatory cytokines of bacterial fractions in relation to disease type | Measurement of proinflammatory cytokines (f.e.: IL-8) in epithelial and dendritic tissue culture assays | one day | 
| Concentration of proinflammatory cytokines of bacterial fractions in other colonic diseases | Measurement of proinflammatory cytokines (f.e.: IL-8) in epithelial and dendritic tissue culture assays | One day |