Irritable Bowel Syndrome
Conditions
Keywords
FODMAP, microbiota, histamine
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.
Interventions
DIETARY_SUPPLEMENTL-Histidine
1 capsule (0.6g) twice daily
DIETARY_SUPPLEMENTHigh-FODMAP beverage
High-FODMAP beverage (10g of fermentable carbohydrates) consumed twice daily.
DIETARY_SUPPLEMENTLow-FODMAP beverage
Low-FODMAP beverage (10g glucose) consumed twice daily.
DIETARY_SUPPLEMENTLactobacillus acidophilus CL1285, L. casei LBC80R and L. rhamnosus CLR2.
Total of 50 billion CFU/capsule taken twice daily.
OTHERPlacebo
Enteric coated capsule with no active ingredient, taken twice daily
Sponsors
McMaster University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Metabolites in stool, urine and blood | six weeks | Metabolites will be measured by LC-MS and ELISA at baseline and before and after each intervention. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Stool microbiota composition | six weeks | 16S rRNA Illumina sequencing of stool samples with culture-enriched sequencing. |
| Worsening of IBS symptoms following High-FODMAP challenge | six weeks | Increase by ≥50 points on IBS Symptom Severity Score (IBS-SSS). The score will be used as a dichotomous variable. The overall score ranges from 0 to 500, with higher scores indicating greater symptom severity. |
| Changes in IBS symptoms | six weeks | IBS-SSS continuous data. The overall score ranges from 0 to 500, with higher scores indicating greater symptom severity. |
| Expression of hdc gene by stool bacteria | six weeks | Gram-positive and Gram-negative bacteria will be assessed by PCR using custom designed primers |
| Levels of anxiety, depression and stress | six weeks | Depression Anxiety Stress Scale (DASS-21) to assess psychiatric comorbidity and stress. The scale scores range from 0 - 42 with higher scores indicating worse outcomes. |
| Changes in dietary intake | six weeks | 5-day food diaries will be completed at 5 time points. FODMAP intake will be quantified using Monash University software and database |
| Changes in general GI symptoms | six weeks | Patient-Reported Outcomes Measurement Information System (PROMIS) for general GI symptoms. Four subscales will be used: Gas & Bloating, Diarrhea, Constipation, and Belly Pain. T-scores are calculated using the Scoring Service by Health Measures and range from 34.7 - 79.0 (Gas & Bloating), 39.9 - 75.2 (Diarrhea), 40.6 - 80.8 (Constipation), and 33.9 - 80.0 (Belly Pain). On this scale, 50 indicates the mean of the general population and a difference of 10 is a standard deviation. Higher scores indicate greater symptom severity. |
Countries
Canada
Contacts
Primary ContactCaroline Seiler, BSc
Backup ContactAndrea Nardelli, PhD
Outcome results
None listed