Microbe-Gut Interaction in Microscopic Colitis and Post-Infectious Irritable Bowel Syndrome (IBS)

Objective: This study aims elucidate the pathophysiological link between the environment in the colon (mainly the microbiota), the local immune system and activation of the enteric nervous system in patients with post-infectious IBS (PI-IBS) and microscopic colitis (MC) with special emphasis on microbial-mucosa interactions and evaluation of the effect on the immune activation/response as well as how afferent gut-brain signalling leads to abdominal discomfort.

Method: The project is based on data from three cohorts of patients, one with PI-IBS and one with MC as well as a gender- and age-matched cohort of healthy individuals. Measurement of perceived sensitivity in the gut will be evaluated by pain-response under mechanical stress using a barostat. The HIT (Human intestinal Tissue)-Chip array will be used to characterize the diversity, stability and functionality of the intestinal microbiota on mucosa level, giving a clue to the interactions with the host and insight to changes leading to the development of the two diseases.

Immunohistochemistry and flowcytometry will be used to analyse the location, frequency and phenotype characteristics of lymphoid- and mast cells. Functional analysis of mucosal lymphocytes activated in vitro by products from the intestinal microbiota will be examined by cytokine production using the LuminexTM system. The Ussing chamber technique will allow investigation of the impact of the microbiota and its metabolites on intestinal barrier functions. In this method the sample has access to stressors under standard conditions.

Study Overview

• Status: Completed
• Conditions: Irritable Bowel Syndrome (IBS)

Detailed Description

We will make a characterization of lymphocytes, mast cells and gut microflora. Depending on these results we will make stimulations of patient biopsies to find if tissue from patients react differently then patients from healthy.

• Study Type: Observational
• Enrollment (Actual): 125

Contacts and Locations

Study Locations

• Sweden
  • Närke
    • Örebro, Närke, Sweden, 70185
      • Orebro University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients will be recruited from clinic (endoskopimotagningen) at Örebro University Hospital.

Description

Inclusion Criteria:

• Over 18 years
• Healthy and not eating any prescription medication except birth control in pill form

Exclusion Criteria:

• Have or had a history of gastrointestinal disease that has required specialist medical care
• Being lactose intolerance
• Have high blood pressure requiring treatment
• Have premenstrual syndrome
• Lose Weight
• Being pregnant or breast-feed

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Healthy controls
Irritable bowel syndrome (IBS)
Microscopic Colitis (MC)
Irritable bowel disease (IBD)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lymphocyte characterization	LPLs and IELs stained with the following flourochrome-conjugated antibodies: anti-CD3-FITC (clone-HIT3a), anti-CD4-FITC/PECy5 (clone-RPA-T4), anti-CD45RA-PE (clone-HI 100), anti-CD45RO-PECy5 (clone-UCHL1), anti-CD19-PE (clone-HIB19) and anti-CD138-FITC (clone-MI15), all from BD Pharmingen (San Diego, CA, USA). Anti-CD8α-ECD (clone-SFCI21Thy2D3) and anti-CD8β-PECy5 (clone-2ST8.5 H7) were purchased from Beckman Coulter (Fullerton, CA, USA) whereas anti-CD38-PECy5 (clone-HIT2), anti-αβTCR-PECy5 (clone-IP26) and anti-γδTCR-PE (clone-B1) were purchased from Biolegend (San Diego, CA, USA). Fluorochrome-conjugated isotype matched control antibodies were used as controls for non-specific staining, and were purchased from BD Pharmingen or Beckman Coulter (IgGκ-FITC, IgG2bκ-PE, IgG1-ECD, IgG2bκ-PECy5, IgG2κ-FITC, IgG1κ-PE, IgG1κ-PECy5, and IgG2a-PECy5).	After one year of initial infection before treatment

Collaborators and Investigators

• Sponsor: Örebro University, Sweden
• Investigators: Principal Investigator: Robert Brummer, MD, PhD, Örebro universitet

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2010
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: November 15, 2010
• First Submitted That Met QC Criteria: February 6, 2013
• First Posted (Estimate): February 8, 2013

Study Record Updates

• Last Update Posted (Actual): February 24, 2021
• Last Update Submitted That Met QC Criteria: February 23, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Syndrome; Irritable Bowel Syndrome; Colitis; Colitis, Microscopic
• Other Study ID Numbers: 2010-05; 2010/261 (Other Identifier: 2010/261 Uppsala etiknämnd)