We will perform a randomized, double-blind, placebo-controlled trial to establish whether calcium butyrate relieves symptoms in children with irritable bowel syndrome (IBS). The direct effects of butyrate on inflammation and GI symptoms will be studied in children with IBS. The design used to study the effects of calcium butyrate will be a double blind randomized placebo-controlled parallel design.

Study plan 2-week run-in phase (weeks 1-2) followed by 8-week treatment period (weeks 3-10) and a 4- week follow-up phase (weeks 11-14).

Randomization Enrolled children will be randomly assigned, with the use of a computer-generated randomization list to receive either oral butyrate (500 mg) or oral placebo once (twice) per day. Placebo and butyrate had the same shape, the placebo's taste, dimension, indication, and appearance.

Data Collection A diary will be given to the parents; on a daily basis, patients will monitor and record the frequency/severity of symptoms and school absence on the diary. To assess the severity of pain, a combination of the self-reported visual analog scale (VAS) and the Faces Pain Scale (FPS) will be used. The 0- to 10-mm VAS scale (0, no pain; 10, worst possible pain) include a horizontal color gradient (green to red) plus a rating. Daily, when asked to evaluate pain, the child would point to a level and trace a line. Assessment will be done coupling the VAS with the FPS, which consists of 6 faces that range from a relaxed face to a face that shows intense pain (von Baeyer CL). GSRS Participants will be asked to fill out the GSRS every 2 weeks during running in, treatment, and follow up (Svedlund).

Compliance To ensure compliance, the investigator will contact the families every 4 weeks to monitor the process of the study.

Adherence will be assessed by counting the number of capsules returned; children who will miss taking more than 20% of the medication will be considered noncompliant.

Fecal Analysis Fecal samples for microbiological analysis will be collected before treatment and at week 10 (end of treatment) and week 14 (4 weeks after discontinuation). Urinary NMR Analysis Urinary samples for NMR analysis will be collected before treatment and at week 10 (end of treatment) and week 14 (4 weeks after discontinuation). This method is described by Lussu et al .

Fecal lactoferrin and calprotectin Fecal calprotectin will be measured using a commercial Fecal Calprotectin Immunoassay kit (Genova Diagnostics, Asheville, NC), respectively, following the manufacturers' instructions.

Sample size calculation To demonstrate an efficacy of butyrate, considering a placebo effect of 20% and a difference in response of at least 35%, keeping a power of the study of 80% and a p of 0,05 we need 23 patients for group that, considering a drop out of 10%, will became 25 per group.

Inclusion Criteria:

• Diagnosis of IBS according to the Rome IV diagnostic criteria

Exclusion Criteria:

• Presence of any chronic diseases
• Treatment with antibiotics/prebiotics/probiotic/postbiotic in the previous two months
• Diagnosis of another functional GI disease
• Growth failure or others alarming signs of organic conditions
• Previous abdominal surgery