The Bacterial Secretome in IBD

The Bacterial Secretome in Crohn's Disease and Ulcerative Colitis

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.

Study Overview

• Status: Completed
• Conditions: Inflammatory Bowel Diseases
• Intervention / Treatment: Other: Colonic fluid collection during endoscopy for analysis of the bacterial secretome

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 74
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria
    • Medical University of Graz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Healthy controls and active and inactive UC patients

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy Controls; 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; 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)
Crohn's disease; 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; 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)
Ulcerative Colitis; 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; 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)
Colorectal carcinoma; 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; 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)
Colitis/Enteritis of other origin; 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; 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)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Medical University of Graz
• Investigators: Principal Investigator: Christoph Hoegenauer, Prof, Medical University of Graz

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2019
• Primary Completion (Actual): July 31, 2024
• Study Completion (Actual): July 31, 2024

Study Registration Dates

• First Submitted: May 10, 2019
• First Submitted That Met QC Criteria: October 21, 2019
• First Posted (Actual): October 23, 2019

Study Record Updates

• Last Update Posted (Actual): March 26, 2025
• Last Update Submitted That Met QC Criteria: March 21, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases
• Other Study ID Numbers: 17-199 ex 05/06

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No