The Stool Microbiome of Treated and Untreated IBS (Irritable Bowel Syndrome) Patients

Generating a Stool Microbiome-based Diagnostic for IBS (Irritable Bowel Syndrome) Patients in Low-FODMAP Treated and Untreated IBS Patients

Irritable bowel syndrome (IBS) is considered the most common gastrointestinal disorder in humans, with an estimated global prevalence of 11%-20% of all humans. Alterations in the gut microbiome are at the center of IBS, and microbiome-induced volatile metabolites in response to dietary exposures is believed to drive a downstream impact on susceptible hosts, thereby driving the disease. However, the characteristics and functions of these metabolites remain unknown to date. The two main mechanisms invoking IBS development and flares include 1) an increase in luminal water content due to malabsorption of small molecules and 2) incrementation of colon gas production generated by the fermentation of small molecules by gut bacteria.Yet to date, a person-specific elucidation of the specific small molecules and bacteria driving IBS, and their downstream effects on the human gut epithelium remain unknown.

Over the past years, it became evident that dietary regimes, and their interactions with the intestinal microbiome, are at the center of IBS symptom generation and alleviation. The most widely used dietary intervention is a highly restrictive diet, the low-Fermentable Oligo-saccharides Di-saccharides Mono-saccharides And Polyols (FODMAP) diet, based on avoidance of multiple food items that contain available fermentable molecules.

The low-FODMAP diet remains an effective line of treatment for IBS patients, yet due to its complexity and unhealthy nature, it remains a last line of treatment and fails to impact the majority of IBS patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Irritable Bowel Syndrome
• Intervention / Treatment: Other: Low FODMAP dietary regimen

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yotam Cohen; Phone Number: +97289529173; Email: Yotam.cohen@weizmann.ac.il
• Study Contact Backup: Name: Shimrit Eliyahu Miller; Email: shimrit.miller@weizmann.ac.il

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male and Female
• Age - 18-70

Exclusion Criteria:

• Consumption of antibiotics 2 months prior to the first day of the experiment.
• Consumption of probiotic supplements 1 month prior to the first day of the experiment.
• Type 1 or type 2 diabetes diagnosis.
• Pregnancy, fertility treatments, breastfeeding 3 months prior to the first day of the study.
• Chronic disease - to the discretion of the study doctor.
• Cancer and recent anticancer treatment.
• Psychiatric disorders - to the discretion of the study doctor.
• IBD (inflammatory bowel diseases).
• Alcohol or substance abuse.
• BMI > 35.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Non-IBS; Participants which are not suffering from IBS symptoms.
Experimental: IBS -low FODMAP; individuals that are diagnosed with IBS according to Rome IV criteria	Other: Low FODMAP dietary regimen; intervention will include a guidance by a clinical dietitian about low FODMAP diet The FODMAP diet has three phases: Elimination - Avoidance from high-FODMAP foods (2-6 weeks); Reintroduction -Structured challenges of specific food groups each time (6-8 weeks).; Maintenance - personalized diet, according to the response in step 2.
No Intervention: FODMAP graduates; Individuals who have practiced a low-FODMAP diet in the past

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IBS-SSS - irritable bowel syndrome severity score system questionnaire	Severity of symptoms as they are scored in the Rome IV IBS-SSS 75 to <175 to indicate mild IBS, 175 to <300 as moderate, and >300 as severe	1 week
IBS-QOL questionnaire - irritable bowel syndrome quality of life questionnaire	Quality of life scores from the Rome IV IBS-QOL 0-100 scale for ease of interpretation with higher scores indicating better IBS specific quality of life	1 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stool microbiome differences between the study arms - using fecal samples of participants	Analysis of stool samples of the different study arms - using shot-gun metagenomics to asses type of microbiota pre and post low-FODMAP diet.	3 months

Collaborators and Investigators

• Sponsor: Weizmann Institute of Science
• Investigators: Principal Investigator: Eran Elinav, Prof, Weizmann Institute of Science

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2023
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): November 1, 2025

Study Registration Dates

• First Submitted: March 2, 2023
• First Submitted That Met QC Criteria: July 23, 2023
• First Posted (Actual): August 2, 2023

Study Record Updates

• Last Update Posted (Actual): August 2, 2023
• Last Update Submitted That Met QC Criteria: July 23, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease; Gastrointestinal Diseases; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Syndrome; Irritable Bowel Syndrome
• Other Study ID Numbers: 1914-4

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No