IBS-Oriented CDED Versus Low FODMAP Diet for Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction characterized by chronic gastrointestinal symptoms in the absence of structural disease. Increasing evidence suggests that, particularly in non-constipated IBS (IBS-D and IBS-M), impaired intestinal barrier function, gut microbiota dysbiosis, mucosal immune activation, and low-grade inflammation contribute to symptom generation. These findings have shifted the focus of research toward dietary strategies that target underlying biological mechanisms rather than symptom reduction alone.

The low FODMAP diet is currently the most extensively studied dietary intervention for IBS and is recommended by international guidelines. However, despite its effectiveness in reducing gastrointestinal symptoms, concerns remain regarding its potential adverse effects on gut microbial diversity and the lack of evidence for improvement in intestinal inflammation or barrier integrity.

The Crohn's Disease Exclusion Diet (CDED) was originally developed for patients with Crohn's disease and has demonstrated favorable effects on intestinal inflammation, epithelial barrier function, and gut microbiota composition. Because several of these biological pathways are also implicated in IBS pathophysiology, an adapted version of the CDED may provide clinical benefits while simultaneously targeting disease mechanisms that are not addressed by current dietary approaches.

This study will evaluate, for the first time, an IBS-oriented adaptation of the CDED that excludes the enteral formula component used in Crohn's disease. In addition to evaluating clinical efficacy, the study will investigate potential biological mechanisms through serial assessment of fecal inflammatory markers, intestinal permeability markers, and gut microbiota composition. By integrating clinical, psychological, and biological outcomes, the study aims to determine whether this dietary intervention represents a mechanism-based alternative to the current dietary standard of care for patients with non-constipated IBS.

Inclusion criteria

• Adults, men, and women (≥18 years) are diagnosed with IBS-D or IBS-M according to Rome IV criteria.
• Moderate-to-severe symptoms (IBS-SSS score ≥175).
• Stable use of any IBS-related medications for ≥6 weeks before study enrollment, except for antibiotics

Exclusion criteria

• Coexisting GI diseases [e.g., Crohn's disease, ulcerative colitis, SIBO, celiac disease [positive transglutaminase (TTG) serology].
• Disease that could explain or influence symptoms or GI function, including diabetes, thyroid disease [abnormal Thyroid-Stimulating Hormone (TSH)], and bariatric surgery.
• Recent intestinal resection.
• Pregnancy or breastfeeding.
• Known food allergies.
• Current active eating disorder
• Participants already following a restrictive diet, including diets that overlap with the interventions in this study, will be excluded to prevent confounding effects on gut microbiota composition and gastrointestinal symptoms, and to ensure consistent baseline conditions. However, individuals who have discontinued such diets at least two to four weeks prior to enrollment may be eligible, allowing for a sufficient dietary washout period to minimize residual effects on the gut microbiota.
• Currently under obesity management medication treatment.
• Vegans
• Use of antibiotics within the 4 weeks prior to enrollment or during the study period.
• Abnormal hemoglobin levels (for women<11.5 gr/dl, for men<13 gr/dl)29
• Baseline CRP≥5