About this trial
The study will investigate the relationship between fecal bile acids, short-chain fatty acids (SCFAs), and the gut microbiota in irritable bowel syndrome (IBS). The central hypothesis of this study is that specific shifts in the GI microbiome composition correlate with altered colonic SCFAs and BAs and contribute to IBS symptoms. Primary aims include: (a) identifying GI microbiome signatures in IBS subtypes (IBS-C and IBS-D) and matched controls, and test if microbiome signatures in these groups correlate with fecal SCFAs and bacterial fermentation of an indigestible carbohydrate (inulin) after a dietary challenge (fecal inulin), and (b) determining if GI microbiome signatures in IBS subtypes and controls correlate with fecal BAs or markers of SCFA production (fecal SCFAs or inulin) and test if BAs correlate with fecal SCFAs or inulin.
The target population is adults ages 18-65 years meeting Rome IV criteria for IBS (both diarrhea- and constipation-predominant, IBS-D and IBS-C) and asymptomatic controls. Primary outcomes will be fecal bile acid excretion and profile, short-chain fatty acid excretion and profile, colonic transit, and fecal microbiota. Secondary outcomes will be stool characteristics based on responses to validated bowel diaries. Stool samples will be collected from participants during the last 2 days of a 4-day 100 g fat diet and split into 3 samples for fecal microbiota, SCFA, and bile acid analysis.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Age 18-75
Individuals with irritable bowel syndrome (IBS)
Healthy volunteers (healthy controls) with no prior history of gastrointestinal (GI) disease or symptoms
No dietary restrictions other than vegetarian
Disqualifiers
Inflammatory bowel disease, celiac disease, or certain types of abdominal cancer, as well as those with thyroid or liver issues
Abdominal surgery or abdominal radiation within 6 months of study participation, with an exception for C-section or gallbladder removal
Use of any prescription, over the counter, or herbal medications known to affect gastrointestinal function or study interpretation, such as opioids, inflammatory drugs or certain antidepressants, within 6 months prior to study participation for healthy volunteers, or within 2 days of study participation for participants with IBS.
An exception will be permitted for limited use of stable low doses of antidepressants for individuals who have been taking them for a period greater than one month.
Trial design
Single group
Treatments tested in this trial
Inulin
Dietary supplementInulin ingestion is not being used to diagnose, treat, or prevent IBS. Inulin is being used to study an individual's ability to ferment dietary fiber.
Treatment groups
Trial outcomes
Primary outcomes
Total fecal bile acids
Stool samples will be collected over 2 days for measurement of fecal bile acids (µmol/48h) by high performance liquid chromatography-mass spectometry.
Total fecal short chain fatty acids
Stool samples will be collected for measurement of measurement of short chain fatty acids (µg/mg) by liquid chromatography-mass spectrometry
Individual fecal short chain fatty acids
Stool samples will be collected for measurement of measurement of short chain fatty acids (µg/mg) by liquid chromatography-mass spectrometry
Fecal microbial population
Stool samples will be be collected from participants for nucleic acid extraction, 16S allele PCR and sequencing to measure microbial communities and profiles of specimens
Secondary outcomes
Percent primary fecal bile acids
Stool samples will be collected over 2 days for measurement of fecal bile acids (µmol/48h) by high performance liquid chromatography-mass spectrometry.
Stool characteristics
Stool characteristics will be measured using a 4 day bowel diary
Other outcomes
24-hour diet (food intake) recall
24-hour dietary intake will be submitted using web-based Automated Self-Administered Dietary Assessment Tool developed by the National Cancer Institute (https://epi.grants.cancer.gov/asa24/).
Sponsors and contacts
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