Effect of a Low FODMAP Diet in IBS and Functional Constipation with Bloating: a Randomized Double-Blind Trial

Effect of a Low FODMAP Diet in Irritable Bowel Syndrome and Functional Constipation with Bloating: a Randomized Double-Blind Controlled Trial with Microbiota, Intestinal Gas, and Metabolomic Analysis

This clinical study aims to evaluate the effects of a low FODMAP diet compared to a high FODMAP diet in patients with Irritable Bowel Syndrome (IBS) and Functional Constipation (FC) with predominant bloating. The study is a randomized, double-blind, controlled trial designed to assess whether a diet low in fermentable carbohydrates can improve bloating symptoms, gut microbiota composition, intestinal gas production, and metabolic outputs.

Patients meeting the Rome IV criteria for IBS or FC with persistent bloating will be enrolled and randomly assigned to receive either a low or high FODMAP diet for two weeks. Meals will be standardized to control FODMAPs composition, ensuring that FODMAP content is the primary variable.

The primary endpoint is the proportion of participants with a ≥30% reduction in bloating severity, measured using the Visual Analog Scale (VAS). Secondary outcomes include changes in global IBS symptoms, abdominal pain, bowel movements, stool consistency, microbiota diversity, hydrogen/methane gas production, and metabolomic profiles.

This study will contribute to the growing body of evidence supporting dietary management in disorders of gut-brain interaction (DGBI), particularly in bloating-predominant IBS and FC, and will provide insights into the mechanisms linking diet, gut microbiota, and symptom improvement.

Study Overview

• Status: Not yet recruiting
• Conditions: Constipation - Functional; Irritable Bowel Syndrome (IBS); Bloating
• Intervention / Treatment: Other: Low FODMAP Diet; Other: High FODMAP Diet

Detailed Description

Irritable Bowel Syndrome (IBS) and Functional Constipation (FC) are chronic Disorders of Gut-Brain Interaction (DGBI) characterized by altered motility, visceral hypersensitivity, dysbiosis, and central nervous system processing abnormalities. Bloating is a challenging and distressing symptom that often persists despite standard pharmacological treatments.

The low FODMAP diet has been widely studied as a dietary approach to alleviate IBS symptoms. FODMAPs (Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols) are poorly absorbed short-chain carbohydrates that increase osmolarity, promote intestinal gas production, and alter gut microbiota, leading to bloating and discomfort. Although studies support the effectiveness of the low FODMAP diet, existing research lacks controlled, blinded trials assessing its impact on bloating-specific symptoms and related physiological markers.

This study addresses these gaps by using a double-blind, controlled design with rigorously standardized meals containing well-defined FODMAP content. It will assess clinical outcomes, gut microbiota composition, gas production, and metabolomic changes to elucidate the mechanisms underlying the diet's effects.

Study Design This is a randomized, double-blind, controlled trial conducted at a single center. Participants will be assigned to receive either a low FODMAP or a high FODMAP diet for two weeks.

Participants:

Adults ≥18 years diagnosed with IBS or FC with persistent bloating based on Rome IV criteria.

Intervention:

Standardized meal plans containing either low FODMAP or high FODMAP content.

Randomization:

Computer-generated block randomization (block of 4)

Blinding:

Investigators, study staff, and participants will remain blinded to the dietary allocation.

Primary Outcome:

≥30% reduction in bloating severity on the VAS scale.

Secondary Outcomes:

Changes in global IBS symptoms (IBS-SSS) or constipation symptoms (PAC-Sym) Abdominal pain (VAS) stool frequency, and consistency (Bristol Stool Form Scale). Gut microbiota diversity and composition (16S rRNA sequencing). Intestinal gas production (hydrogen/methane breath test). Metabolomic analysis (short-chain fatty acids, urine histamine, azelaic acid). Use of rescue medications for symptom relief.

Study Procedures

Baseline Assessment:

Demographic data, medical history, and dietary habits (7-day food diary). Baseline bloating severity, stool consistency, and quality of life (IBS-QoL, PAC-QoL).

Microbiota, breath test, and metabolomic sampling.

Intervention Phase (2 Weeks):

Participants consume standardized low or high FODMAP meals (3 main meals + 1 snack/day).

Daily recording of symptoms, bowel movements, and use of rescue medications.

Follow-up Assessments:

Week 1: Phone follow-up to assess adherence and symptom progression. Week 2: Final clinical and laboratory assessments (identical to baseline). Data collection for statistical analysis comparing treatment effects.

Statistical Analysis Primary endpoint (bloating reduction) analyzed using Chi-square/Fisher's exact test.

Secondary outcomes analyzed with paired t-tests, Mann-Whitney U tests, and logistic regression.

Microbiota diversity assessed using Shannon index, beta diversity, and PERMANOVA testing.

Significance and Impact This study will provide high-quality evidence on the effectiveness of the low FODMAP diet for bloating-predominant IBS and FC, addressing critical knowledge gaps. By integrating clinical, microbiota, and metabolomic data, it will enhance understanding of diet-microbiota interactions and their role in symptom modulation.

• Study Type: Interventional
• Enrollment (Estimated): 34
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Monthira Maneerattanaporn, MD; Phone Number: 662419777; Email: monthira.man@mahidol.ac.th
• Study Contact Backup: Name: Tanawat Geeratragool, MD; Phone Number: 66823430096; Email: tanawat.grtg@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 years
• Diagnosed with Irritable Bowel Syndrome (IBS) or Functional Constipation (FC) based on Rome IV criteria
• Persistent bloating affecting daily life, with a bloating VAS score ≥4
• Stable bowel habits with Bristol Stool Form Scale (BSFS) type 3-5
• History of prior treatment with antispasmodics and/or prokinetics (allowed if dose remains stable)
• Able to comply with dietary intervention and study procedures

Exclusion Criteria:

• Prior gastrointestinal surgery (except appendectomy or cholecystectomy)
• Use of antibiotics, proton pump inhibitors (PPIs), probiotics, NSAIDs, lactulose, or metformin within the past 4 weeks
• Presence of systemic diseases affecting gut microbiota (e.g., liver cirrhosis, uncontrolled diabetes, end-stage renal disease, obesity, cancer, psychiatric disorders)
• Inability to consume study meals or follow dietary restrictions

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low FODMAP Diet; Participants will follow a low FODMAP diet for two weeks, consuming standardized meals with minimal fermentable carbohydrates. Meals match the high FODMAP diet in appearance to maintain blinding.	Other: Low FODMAP Diet; A standardized diet containing low levels of fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs), designed to reduce bloating and gastrointestinal symptoms. Meals are pre-prepared, calorie-matched, and visually identical to those in the high FODMAP group to maintain blinding. Participants will consume three main meals and one snack daily for two weeks, with adherence monitored through food diaries and photos.
Active Comparator: High FODMAP Diet; Participants will follow a high FODMAP diet for two weeks, consuming standardized meals with high fermentable carbohydrates. Meals match the low FODMAP diet in appearance to maintain blinding.	Other: High FODMAP Diet; A standardized diet containing high levels of fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) to assess its impact on bloating and gastrointestinal symptoms. Meals are calorie-matched and visually identical to those in the low FODMAP group to maintain blinding. Participants will consume three main meals and one snack daily for two weeks, with adherence tracked through food diaries and photos.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Bloating Severity (VAS)	The primary outcome is the change in bloating severity, measured using the Visual Analog Scale (VAS). The VAS score ranges from 0 (no bloating) to 10 (severe bloating), with higher scores indicating worse bloating symptoms. Participants will record daily bloating scores throughout the intervention period. The proportion of participants achieving a ≥30% decrease in bloating severity from baseline will be analyzed.	Baseline to 2 weeks (End of Intervention)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction in Global IBS Symptoms (IBS-SSS)	Change in IBS Symptom Severity Score (IBS-SSS) from baseline, assessing overall IBS symptom burden, abdominal pain, bloating, and bowel habit changes. The IBS-SSS scale ranges from 0 to 500, with higher scores indicating more severe IBS symptoms.	Baseline to 2 weeks
Change in Abdominal Pain (VAS)	Change in abdominal pain severity, measured using the Visual Analog Scale (VAS). The VAS scale ranges from 0 (no pain) to 10 (severe pain), with higher scores indicating worse pain severity. Participants will record daily pain scores, and the difference between baseline and post-intervention scores will be analyzed.	Baseline to 2 weeks
Change in Stool Frequency and Consistency	Change in bowel movement frequency and stool consistency, assessed using the Bristol Stool Form Scale (BSFS). Stool frequency will be recorded as the number of bowel movements per day. Stool consistency will be graded using the BSFS scale (1-7): 1-2: Hard stools (constipation) 3-4: Normal stools 5-7: Loose stools (diarrhea) Higher BSFS scores indicate looser stool consistency. The difference between baseline and post-intervention values will be analyzed.	Baseline to 2 weeks
Changes in Gut Microbiota Composition	Alterations in gut microbiota diversity and abundance (16S rRNA sequencing).	Baseline to 2 weeks
Change in Hydrogen Gas Production (Lactulose Breath Test)	Change in exhaled hydrogen (H₂) levels, measured via lactulose breath test in parts per million (ppm). Higher hydrogen levels indicate increased fermentation by colonic microbiota.	Baseline to 2 weeks
Change in Methane Gas Production (Lactulose Breath Test)	Change in exhaled methane (CH₄) levels, measured via lactulose breath test in parts per million (ppm). Elevated methane levels are associated with slow colonic transit and constipation.	Baseline to 2 weeks
Use of Rescue Medications	Frequency and dosage of antispasmodics, prokinetics, or laxatives used for symptom relief.	Baseline to 2 weeks
Change in Psychological Symptoms (DASS-21)	Change in Depression, Anxiety, and Stress Scores (DASS-21), a validated self-reported scale measuring psychological distress. The DASS-21 consists of three subscales: Depression (0-21) Anxiety (0-21) Stress (0-21) Each subscale score ranges from 0 (normal) to 21 (severe symptoms), with higher scores indicating greater psychological distress. The total score is calculated by summing individual subscale scores.	Baseline to 2 weeks
Change in Quality of Life (IBS-QoL / PAC-QoL)	Change in IBS-specific Quality of Life (IBS-QoL) score, which assesses the impact of IBS on daily activities, emotional well-being, and social functioning. The IBS-QoL score ranges from 0 to 100, with higher scores indicating better quality of life.	Baseline to 2 weeks
Patient Satisfaction with Treatment	Overall treatment satisfaction, measured using a Visual Analog Scale (VAS) ranging from 0 to 10: 0 = Completely Dissatisfied 10 = Completely Satisfied Higher scores indicate greater satisfaction with treatment. The difference between baseline and post-intervention scores will be analyzed.	Baseline to 2 weeks
Change in Patient-Reported Constipation Symptoms (PAC-SYM)	Change in Patient Assessment of Constipation-Symptoms (PAC-SYM) score, evaluating constipation-related symptoms, including stool consistency, discomfort, and straining. The PAC-SYM scale ranges from 0 to 48, with higher scores indicating worse constipation symptoms.	Baseline to 2 weeks
Change in Short-Chain Fatty Acids (SCFAs) Levels	Change in fecal short-chain fatty acids (SCFAs), including acetic acid, propionic acid, and butyric acid, measured in μmol/g stool. Higher SCFA levels indicate greater microbial fermentation activity.	Baseline to 2 weeks
Change in Urine Histamine Levels	Change in urine histamine concentration, measured in μg/mL urine, assessing histamine metabolism related to gut inflammation and microbiota activity. Higher levels indicate increased histamine production.	Baseline to 2 weeks
Change in Urine Azelaic Acid Levels	Change in urine azelaic acid concentration, measured in μg/mL urine, assessing microbial metabolic changes associated with gut dysbiosis and inflammation. Higher levels indicate altered microbial metabolism.	Baseline to 2 weeks
Change in Constipation-Specific Quality of Life (PAC-QoL)	Change in Patient Assessment of Constipation-Quality of Life (PAC-QoL) score, evaluating the impact of constipation on daily life, physical discomfort, psychological well-being, and social aspects. The PAC-QoL score ranges from 0 to 100, with higher scores indicating better quality of life.	Baseline to 2 weeks

Collaborators and Investigators

• Sponsor: Mahidol University
• Investigators: Study Director: Monthira Maneerattanaporn, MD, Mahidol University Faculty of Medicine Siriraj Hospital; Principal Investigator: Tanawat Geeratragool, MD, Mahidol University Faculty of Medicine Siriraj Hospital; Study Chair: Somchai Leelakusolvong, MD, Mahidol University Faculty of Medicine Siriraj Hospital

Publications and helpful links

General Publications

• Varney J, Barrett J, Scarlata K, Catsos P, Gibson PR, Muir JG. FODMAPs: food composition, defining cutoff values and international application. J Gastroenterol Hepatol. 2017 Mar;32 Suppl 1:53-61. doi: 10.1111/jgh.13698.
• Drossman DA, Tack J. Rome Foundation Clinical Diagnostic Criteria for Disorders of Gut-Brain Interaction. Gastroenterology. 2022 Mar;162(3):675-679. doi: 10.1053/j.gastro.2021.11.019. Epub 2021 Nov 19. No abstract available.
• Camilleri M. Diagnosis and Treatment of Irritable Bowel Syndrome: A Review. JAMA. 2021 Mar 2;325(9):865-877. doi: 10.1001/jama.2020.22532. Erratum In: JAMA. 2021 Apr 20;325(15):1568. doi: 10.1001/jama.2021.4833.
• Andrews CN, Sidani S, Marshall JK. Clinical Management of the Microbiome in Irritable Bowel Syndrome. J Can Assoc Gastroenterol. 2020 Jan 4;4(1):36-43. doi: 10.1093/jcag/gwz037. eCollection 2021 Feb.
• Muir JG, Shepherd SJ, Rosella O, Rose R, Barrett JS, Gibson PR. Fructan and free fructose content of common Australian vegetables and fruit. J Agric Food Chem. 2007 Aug 8;55(16):6619-27. doi: 10.1021/jf070623x. Epub 2007 Jul 11.

Study record dates

Study Major Dates

• Study Start (Estimated): March 15, 2025
• Primary Completion (Estimated): March 15, 2026
• Study Completion (Estimated): July 31, 2026

Study Registration Dates

• First Submitted: February 28, 2025
• First Submitted That Met QC Criteria: March 6, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 6, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Microbiota; Irritable Bowel Syndrome (IBS); FODMAP; Functional Constipation
• 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; Constipation
• Other Study ID Numbers: Si 148/2025

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
• product manufactured in and exported from the U.S.: No