Fecal Metabolome and the Intestinal Microbiota in Irritable Bowel Syndrome (IBS)

Fecal Bile Acids, Fecal Short Chain Fatty Acids and the Intestinal Microbiota in Patients With Irritable Bowel Syndrome and Control Volunteers

The purpose of this study is to find out the relationship between the bile acids, fatty acids (fatty acids are part of the diet) and bacteria that are present in the intestines.

Study Overview

• Status: Completed
• Conditions: IBS
• Intervention / Treatment: Radiation: X-Ray

Detailed Description

There is emerging evidence that alterations in bile acids and SCFA associated with IBS could be associated with changes in the gut microbiota. In addition to modulating levels of intraluminal organic acids, it has been hypothesized that gut microbiota may alter local immune responses, modulate visceral pain responses, and impair gut barrier function.

Our overall goal is to investigate the relationship between fecal bile acids, SCFA and the gut microbiota in IBS. Results of this pilot study could reveal insights into the interplay of the gut microbiota and small molecule mediators of IBS to suggest targeted clinical strategies for improved diagnosis and management of this important syndrome.

AIM 1: Test the hypothesis that fecal organic acids (SFCA and bile acids) and fecal microbiota play an important role in IBS.

AIM 2: Test the hypothesis that there is association between colonic transit and fecal microbiota in IBS

• Study Type: Observational
• Enrollment (Actual): 100

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The target study population will be patients with IBS (both diarrhea- and constipation-predominant) and healthy controls.

Description

Inclusion Criteria:

• Patients with IBS, ages 18-65 fulfilling Rome IV criteria and asymptomatic controls with no prior history of GI disease or symptoms.
• Participants should be on a stable and consistent diet regimen and should not be following an extreme diet intervention such as gluten-free or a low FODMAP diet at the time of study participation.

Exclusion Criteria:

• Participants with microscopic/lymphocytic/collagenous colitis, inflammatory bowel disease, celiac disease, visceral cancer, chronic infectious disease, immunodeficiency, uncontrolled thyroid disease, history of liver disease or history of elevated AST/ALT > 2.0x the upper limit of normal
• Prior radiation therapy of the abdomen or abdominal surgeries with the exception of appendectomy or cholecystectomy > 6 months prior to study initiation
• Ingestion of any prescription, over the counter, or herbal medications which can affect GI transit or study interpretation (e.g. opioids, narcotics, anticholinergics, norepinephrine reuptake inhibitors, nonsteroidal anti-inflammatory drugs, COX-2 inhibitors, bile acid sequestrants) within 6 months of study initiation for asymptomatic volunteers or within 2 days before study initiation for IBS patients
• Any females who are pregnant or trying to become pregnant or breast-feeding
• Antibiotic usage within 3 months prior to study participation
• Prebiotic or probiotic usage within the 2 weeks prior to study initiation
• Use of tobacco products within the past 6 months.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
IBS-C; all patients with IBS -C will undergo an abdominal x-ray for assessment of colonic transit	Radiation: X-Ray; X-ray of the abdomen will be performed to assess colonic transit
IBS-D; all patients with IBS-D will undergo an abdominal x-ray for assessment of colonic transit	Radiation: X-Ray; X-ray of the abdomen will be performed to assess colonic transit
heathy control; all healthy controls will undergo an abdominal x-ray for assessment of colonic transit	Radiation: X-Ray; X-ray of the abdomen will be performed to assess colonic transit

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total and individual fecal bile acid excretion	Stool samples will be collected over 2 days for measurement of fecal bile acids (µmol/48h) by high performance liquid chromatography-mass spectometry	two days
Total fecal excretion of 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	two days
Fecal microbial population and community from stool collection	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	two days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fecal excretion of individual 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	two days
Stool characteristics	Stool characteristics will be measured using a 14 day bowel diary	14 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall and segmental colon transit	Colonic transit time will be measured in days using radiopaque markers	7 days

Collaborators and Investigators

• Sponsor: Indiana University
• Investigators: Principal Investigator: Andrea Shin, MD, Indiana University

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2016
• Primary Completion (Actual): April 27, 2023
• Study Completion (Actual): April 27, 2023

Study Registration Dates

• First Submitted: October 31, 2016
• First Submitted That Met QC Criteria: November 30, 2016
• First Posted (Estimated): December 5, 2016

Study Record Updates

• Last Update Posted (Actual): April 29, 2024
• Last Update Submitted That Met QC Criteria: April 25, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Irritable Bowel Syndrome
• Other Study ID Numbers: 1606244063