Effects of Low FODMAP Diet on Colonic Epithelial Physiology in Diarrhea-predominant Irritable Bowel Syndrome

This research is studying whether changing an individual's diet may have an impact as a treatment or outcome for Irritable Bowel Syndrome (IBS). This research will show if diet might play a role in triggering changes that may cause IBS. This study is being done to learn if a low FODMAP (fermentable, oligosaccharides, disaccharides, monosaccharides, and polyols) diet causes changes in the colon lining which mediates improvement in IBS symptoms.

Study Overview

• Status: Completed
• Conditions: Irritable Bowel Syndrome
• Intervention / Treatment: Other: a low FODMAP diet for 4 weeks

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Normal serum studies including serum tissue-transglutaminase antibodies, thyroid stimulating hormone levels, C-reactive protein or fecal calprotectin, complete blood count since the onset of symptoms.
• Normal stool studies including, ova and parasites since the onset of symptoms
• IBS-SSS score of ≥175 at the end of the 7-day screening period

In case of presence of any alarm features and/or elevated inflammatory markers (C-reactive protein or fecal calprotectin), patients will be eligible if they have been excluded for inflammatory bowel disease with colonoscopy in the last one year.

Exclusion criteria

• individuals already on a LFD or other dietary restriction such as gluten free diet within the past 6 months
• individuals with any known food allergy or insulin-dependent diabetes
• known history of celiac disease, inflammatory bowel disease or microscopic colitis
• prior small bowel or colonic surgery or cholecystectomy
• pregnant patients
• Antibiotics in the past 3 months
• Those who regularly use mast cell stabilizers or anti-histaminic or non-steroidal anti-inflammatory agents (NSAIDs) excluding daily baby aspirin or steroids or bile-acid binder.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study patients with IBS-D; Patients with diarrhea-predominant IBS who will undergo a low FODMAP diet for 4 weeks	Other: a low FODMAP diet for 4 weeks; low FODMAP diet for 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lactulose Mannitol Excretion	Changes in cumulative excretion of lactulose and mannitol in timed urine collection before and after low FODMAP diet measured during 8-24h	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Epithelial Permeability - Tight Junction Gene Expression	Changes in tight junction (TJ) gene expression in colonic biopsies before and after low FODMAP diet Gene expression of Tight junction proteins were normalized to that of Glyceraldehyde 3-phosphate dehydrogenase (GAPDH).	4 weeks
Changes in Epithelial Permeability - Quantitative Tight Junction Immunostaining	Changes in Quantitative tight junction immunostaining of tight junctions in colonic biopsies before and after low FODMAP diet Data is reported as ratio of TJ proteins to NA-K ATPase.	4 weeks
Changes in Stool Microbiome - Alpha Diversity	Changes in relative abundance of bacteria before and after low FODMAP diet. Alpha diversity was measured as number of Amplicon Sequence Variant (ASV) measured in the specimen.	4 weeks
Changes in Stool Microbiome - Beta Diversity	Changes in relative abundance of bacteria before and after low FODMAP diet. For the beta diversity, an analysis of similarities (ANOSIM)test based on Bray-Curtis distances is the best measure if the communities were different. The ANOSIM R statistic gives the scale of difference. ANOSIM R ranges from -1 to 1, where 1 means there is most interparticipant similarity within the group compared with between the different groups, and where -1 means there is least interparticipant similarity within the group compared with between the different groups. A value close to 0 indicates no significant difference between groups, meaning the dissimilarity is similar both within and between groups	4 weeks
Immunohistochemistry for Mast Cells	Number of mast cells in sample after immunohistochemistry were counted.	4 weeks
Gastrointestinal Patient Reported Outcomes Measurement Information System (PROMIS)	PROMIS scales of Belly pain (5a) and diarrhea (6a) will be administered to assess the severity of belly pain and diarrhea in our patients. PROMIS Belly pain questionnaire and PROMIS diarrhea questionnaire have five and six questions, respectively, which assess symptom severity on a 5 point Likert scale. 50 indicates the general population mean with a standard deviation of 10. Higher T-scores on these questionnaires refer to more severe gastrointestinal symptoms. PROMIS belly pain asks how often did you have belly pain, severity of belly pain, interference with activities, bothersomeness and discomfort. PROMIS diarrhea asks how many days did you have loose stools, interference with activities, bothersomeness, and how often you experience urgency.	4 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Irritable Bowel Syndrome Severity Scoring System (IBS-SSS) - 4-Week	Measure Description: IBS-SSS is a scale for assessing overall IBS symptom severity. It includes 5 questions concerning symptoms over the past 10 days: average severity of abdominal pain, # of days with abdominal pain, average severity of abdominal distension or bloating, satisfaction with bowel habits, and the overall interference in their quality of life from these symptoms. Questions are scored on a 0-100 scale and are summed to a total score between 0-500. Lower scores indicate lower symptom severity. Participants were separated into arms based on the change in their responses from baseline to 4 weeks.	4 weeks

Collaborators and Investigators

• Sponsor: University of Michigan
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Prashant Singh, University of Michigan

Study record dates

Study Major Dates

• Study Start (Actual): August 3, 2020
• Primary Completion (Actual): May 15, 2024
• Study Completion (Actual): May 15, 2024

Study Registration Dates

• First Submitted: September 1, 2020
• First Submitted That Met QC Criteria: September 1, 2020
• First Posted (Actual): September 9, 2020

Study Record Updates

• Last Update Posted (Actual): July 30, 2025
• Last Update Submitted That Met QC Criteria: July 10, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Signs and Symptoms, Digestive; Intestinal Diseases; Disease; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Colonic Diseases, Functional; Irritable Bowel Syndrome; Syndrome; Diarrhea
• Other Study ID Numbers: HUM00166423; K23DK129327 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No