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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Другое 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.
• Другое 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.

Первичные конечные точки

• Change in Bloating Severity (VAS) [Срок оценки: Baseline to 2 weeks (End of Intervention)]

Вторичные конечные точки (12)

• Reduction in Global IBS Symptoms (IBS-SSS) [Срок оценки: Baseline to 2 weeks]
• Change in Abdominal Pain (VAS) [Срок оценки: Baseline to 2 weeks]
• Change in Stool Frequency and Consistency [Срок оценки: Baseline to 2 weeks]
• Changes in Gut Microbiota Composition [Срок оценки: Baseline to 2 weeks]
• Change in Hydrogen Gas Production (Lactulose Breath Test) [Срок оценки: Baseline to 2 weeks]
• Change in Methane Gas Production (Lactulose Breath Test) [Срок оценки: Baseline to 2 weeks]
• Use of Rescue Medications [Срок оценки: Baseline to 2 weeks]
• Change in Psychological Symptoms (DASS-21) [Срок оценки: Baseline to 2 weeks]
• Change in Quality of Life (IBS-QoL / PAC-QoL) [Срок оценки: Baseline to 2 weeks]
• Patient Satisfaction with Treatment [Срок оценки: Baseline to 2 weeks]
• Change in Patient-Reported Constipation Symptoms (PAC-SYM) [Срок оценки: Baseline to 2 weeks]
• Change in Short-Chain Fatty Acids (SCFAs) Levels [Срок оценки: Baseline to 2 weeks]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• 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. PMID 34808139
• 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. PMID 33651094
• 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. PMID 33644675
• 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. PMID 28244665
• 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. PMID 17625872

Идентификаторы

NCT: NCT06871748 · Si 148/2025

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗