Calcium butyrate efficacy in pediatric irritable bowel syndrome: Randomized placebo-controlled multiomics-based clinical trial.

Abstract

Objective: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders, and treatment involves nonpharmacological and pharmacological therapies, even if there is no optimal therapy. This randomized, placebo-controlled, double-blind trial aimed to evaluate the efficacy of calcium butyrate supplementation in reducing IBS symptoms and to assess its effects on gut microbiota composition and relative metabolic profiles through a multiomics approach.

Methods: Children aged 4-17 years with IBS diagnosed according to the Rome IV criteria were randomized to receive either a formulation based on calcium butyrate (500 mg/day) or placebo for 8 weeks, followed by a 4-week follow-up period. Clinical assessments included the visual analogue scale (VAS) and gastrointestinal symptom rating scale (GSRS). Fecal samples were analyzed via 16S metataxonomics and targeted/untargeted metabolomics. The primary outcome was an ≥50% reduction in the VAS scores. Secondary outcomes included microbiota composition changes and metabolite profile alterations.

Results: Fifty-one children were enrolled. Treatment success was significantly higher in the butyrate group (73% vs. 3.8%, p < 0.0001). VAS and GSRS scores were significantly reduced in butyrate-treated patients at the end of treatment and postwashout. Metataxonomic analysis revealed increased short chain fatty acids-producing bacteria, including Lachnospiraceae and Ruminococcus gauvreauii, while pro-inflammatory taxa such as Ruminococcus gnavus decreased. Metabolomics confirmed significant changes in SCFA and VOCs, supporting microbiota modulation.

Discussion: Calcium butyrate supplementation effectively reduced IBS symptoms and induced beneficial microbiota and metabolic shifts in pediatric patients. These findings support butyrate as a potential therapy in pediatric IBS, warranting further large-scale investigations to confirm efficacy and optimize dosing strategies.

Clinical trial identification number: Study registered on: https://ClinicalTrials.gov. Number of registration: NCT04566679 Date of registration: 28/09/2020. Date of first enrollment of patients: 01/05/2021.