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

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.

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.

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.

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.

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.