Biomarkers of Diet-microbiota Interactions in Irritable Bowel Syndrome

NCT04364750 | Completed Early Phase 1

• 1 other identifier: BFIBS
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

Most patients suffering from the irritable bowel syndrome (IBS) report that ingestion of certain foods is a major trigger of symptoms, but the reason is unclear. Previous studies have shown that foods containing poorly absorbed carbohydrates (FODMAPs) are fermented by the bacteria in our bowels and these cause symptoms in some but not all patients. Gut bacteria are capable of producing various products, such as neuroimmune mediator histamine, that may be related to IBS symptoms. Our recent data suggest that consumption of FODMAPs promotes production of bacterial histamine. The main objective of this study is to investigate bacterial production of histamine and its relationship to IBS symptoms. The study will involve 6 weeks on a low-FODMAP diet with three three-day interventions consisting of High- or Low-FODMAP drinks along with probiotics or placebo capsules. The patient's bacteria and metabolites will be analyzed at various time points.

Conditions

Irritable Bowel Syndrome

Keywords

FODMAP; microbiota; histamine

Outcome Measures

Primary Outcomes (1)

• Metabolites in stool, urine and blood

  Metabolites will be measured by LC-MS and ELISA at baseline and before and after each intervention.

  six weeks

Secondary Outcomes (7)

• Expression of hdc gene by stool bacteria

  six weeks

• Stool microbiota composition

  six weeks

• Worsening of IBS symptoms following High-FODMAP challenge

  six weeks

• Changes in IBS symptoms

  six weeks

• Changes in general GI symptoms

  six weeks

Study Arms (3)

Group A

EXPERIMENTAL

Participants in group A will undergo challenges in the order: 1. High-FODMAP beverage + placebo probiotic + L-Histidine 2. Low-FODMAP beverage + placebo probiotic + L-Histidine 3. High-FODMAP beverage + probiotic + L-Histidine Challenges each last 5 days, but the FODMAP drinks and the L-Histidine capsules are only taken for the last three days. There is a 10 day washout period between challenges.

Dietary Supplement: L-Histidine; Dietary Supplement: High-FODMAP beverage; Dietary Supplement: Low-FODMAP beverage; Dietary Supplement: Lactobacillus acidophilus CL1285, L. casei LBC80R and L. rhamnosus CLR2.; Other: Placebo

Group B

EXPERIMENTAL

Participants in group A will undergo challenges in the order: 1. Low-FODMAP beverage + placebo probiotic + L-Histidine 2. High-FODMAP beverage + probiotic + L-Histidine 3. High-FODMAP beverage + placebo probiotic + L-Histidine. Challenges each last 5 days, but the FODMAP drinks and the L-Histidine capsules are only taken for the last three days. There is a 10 day washout period between challenges.

Dietary Supplement: L-Histidine; Dietary Supplement: High-FODMAP beverage; Dietary Supplement: Low-FODMAP beverage; Dietary Supplement: Lactobacillus acidophilus CL1285, L. casei LBC80R and L. rhamnosus CLR2.; Other: Placebo

Group C

EXPERIMENTAL

Participants in group A will undergo challenges in the order: 1. High-FODMAP beverage + probiotic + L-Histidine 2. High-FODMAP beverage + placebo probiotic + L-Histidine 3. Low-FODMAP beverage + placebo probiotic + L-Histidine. Challenges each last 5 days, but the FODMAP drinks and the L-Histidine capsules are only taken for the last three days. There is a 10 day washout period between challenges.

Dietary Supplement: L-Histidine; Dietary Supplement: High-FODMAP beverage; Dietary Supplement: Low-FODMAP beverage; Dietary Supplement: Lactobacillus acidophilus CL1285, L. casei LBC80R and L. rhamnosus CLR2.; Other: Placebo

Interventions

L-Histidine DIETARY_SUPPLEMENT

1 capsule (0.6g) twice daily

Group A; Group B; Group C

High-FODMAP beverage DIETARY_SUPPLEMENT

High-FODMAP beverage (10g of fermentable carbohydrates) consumed twice daily.

Group A; Group B; Group C

Low-FODMAP beverage DIETARY_SUPPLEMENT

Low-FODMAP beverage (10g glucose) consumed twice daily.

Group A; Group B; Group C

Lactobacillus acidophilus CL1285, L. casei LBC80R and L. rhamnosus CLR2. DIETARY_SUPPLEMENT

Total of 50 billion CFU/capsule taken twice daily.

Also known as: Bio-K+ 50 Billion

Group A; Group B; Group C

Placebo OTHER

Enteric coated capsule with no active ingredient, taken twice daily

Group A; Group B; Group C

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults aged 18-75 with IBS (Rome IV criteria) who have self-reported previous improvement in their IBS symptoms while on a low FODMAP diet, or when excluding certain high-FODMAP foods, or patients in whom histamine is expected to play a key role (either diagnosed with high histamine producing bacteria, or improved IBS symptoms after using antihistamines). Individuals should be able to swallow size 00 capsules.

You may not qualify if:

• Concurrent significant organic GI pathology (i.e. celiac, IBD, etc.)
• Concurrent systemic disease (such as diabetes) and/or laboratory abnormalities considered by investigators to be risky or that could interfere with data collection
• History of active cancer in the last 5 years, other than basal cell cancer
• Pregnant or breastfeeding women
• Active or recent participation (\< 1 month) in a clinical study, except for SPOR IMAGINE
• Use of antibiotics, probiotics, or ACE inhibitors during, or one month prior to the study
• Use of new medications less than 4 weeks prior to the study.
• Allergies to any of the ingredients used in the study
• Any immune-compromising conditions

Sponsors & Collaborators

• McMaster University: lead

Study Sites (2)

McMaster University Medical Centre

Hamilton, Ontario, L8N 3Z5, Canada

Location

Kingston Health Sciences Centre

Kingston, Ontario, K7L 2V7, Canada

Location

MeSH Terms

Conditions

Irritable Bowel Syndrome

Interventions

Histidine

Condition Hierarchy (Ancestors)

Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential

Study Officials

• Premysl Bercik, MD

  McMaster University

  PRINCIPAL INVESTIGATOR

• Stephen Vanner, MD

  Queens University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2020
• First Posted: April 28, 2020
• Study Start: July 15, 2021
• Primary Completion: February 10, 2026
• Study Completion: February 10, 2026
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2)