Microbiome Fructan Metabolism and Symptoms in Childhood IBS

Study Overview
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Brief Summary
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This study evaluates whether the gut microbiome is involved in determining whether children with irritable bowel syndrome (IBS) develop worsening GI symptoms (e.g. pain) when given fructans (a sugar often found in wheat). Participants will both receive a diet with fructans and a diet without fructans.

Detailed Description
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Fructans (fructo-oligosaccharides) are a type of carbohydrate which can not be hydrolyzed by humans. It is commonly found in wheat in the American diet. After ingestion they arrive essentially intact into the colon where they are metabolized by the colonic microbiome. Fructan avoidance has been found to help decrease gastrointestinal symptoms (e.g. pain) in those with IBS. However not all individuals with IBS have worsening symptoms when eating fructans in their diet. This study seeks to evaluate whether the microbiome is involved in determining whether an individual with IBS has worsening symptoms with fructan ingestion. Following a one week baseline period, participants will be randomized in a double-blind cross-over fashion to either a 72 hour meal period with fructans or a 72 hour meal period with maltodextrin (placebo). A washout period of at least 10 days will occur in between. Symptoms will be captured using a stool and pain diary. Stool specimens and urine specimens will be obtained at baseline and during the dietary interventions. Breath hydrogen testing will be obtained during the dietary interventions.

Official Title
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Intestinal Microbiome Fructan Metabolism and Symptom Generation in Childhood IBS

Conditions
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Irritable Bowel Syndrome (IBS)

Intervention / Treatment
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* Other: Fructan
* Other: Maltodextrin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children ages 7-17 years Children with IBS will meet Rome III criteria per the Rome III questionnaire Healthy children will not have chronic conditions English speaking and able to read/write in English Exclusion Criteria: Previous bowel surgery Documented gastrointestinal disorder (e.g. ulcerative colitis) Serious chronic medical condition (e.g. diabetes) Weight and/or height are greater than or less than 2 standard deviations for age Chronic conditions with GI symptoms (e.g. cystic fibrosis) Antibiotics within the past 3 months Pregnancy Autism spectrum disorder and/or significant developmental delay Mood disorders (e.g. major depression) Known post-infectious etiology

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Fructan<br>Fructans will be provided for 72 hours. | Other: Fructan<br>* Short-chain oligosaccharide primarily composed of fructose polymers<br>* Other names: fructo-oligosaccharides;|
| Placebo Comparator: Maltodextrin<br>Maltodextrin will be provided for 72 hours. | Other: Maltodextrin<br>* Polysaccharide produced from starch<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Operational Taxonomic Units (microbiome composition derived from 16s rRNA sequencing) | Children with IBS who have worsening GI symptoms with fructans vs. those who do not | Three days | 
| Microbiome metabolic signatures related to fructan metabolism | Children with IBS who have worsening GI symptoms with fructans vs. those who do not | Three days | 
| Metabolic products of fructan metabolism | In those with IBS who have worsening symptoms when given fructans, the investigators will correlate fructan metabolic byproducts with GI symptoms (e.g. pain) | Three days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microbiome related signatures | Healthy children will have their microbiome signatures (composition, metabolic signatures related to fructan metabolism, and metabolic products of fructan metabolism) compared to children with IBS | Three days | 
| Overall microbiome metabolic signatures | Children with IBS who have worsening GI symptoms vs. those who do not | Three days | 
| Overall metabolic products | Following a fructan challenge in children with IBS who develop worsening GI symptoms vs. those who do not | Three days | 
| Breath hydrogen and methane production symptoms | Children with IBS who have worsening GI symptoms when given fructans vs. those who do not | Three days |