Randomised clinical trial: gut microbiome biomarkers are associated with clinical response to a low <scp>FODMAP</scp> diet in children with the irritable bowel syndrome

<jats:title>Summary</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>A low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (<jats:styled-content style="fixed-case">FODMAP</jats:styled-content>) diet can ameliorate symptoms in adult irritable bowel syndrome (<jats:styled-content style="fixed-case">IBS</jats:styled-content>) within 48 h.</jats:p></jats:sec><jats:sec><jats:title>Aim</jats:title><jats:p>To determine the efficacy of a low <jats:styled-content style="fixed-case">FODMAP</jats:styled-content> diet in childhood <jats:styled-content style="fixed-case">IBS</jats:styled-content> and whether gut microbial composition and/or metabolic capacity are associated with its efficacy.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>In a double‐blind, crossover trial, children with Rome <jats:styled-content style="fixed-case">III IBS</jats:styled-content> completed a 1‐week baseline period. They then were randomised to a low <jats:styled-content style="fixed-case">FODMAP</jats:styled-content> diet or typical American childhood diet (<jats:styled-content style="fixed-case">TACD</jats:styled-content>), followed by a 5‐day washout period before crossing over to the other diet. <jats:styled-content style="fixed-case">GI</jats:styled-content> symptoms were assessed with abdominal pain frequency being the primary outcome. Baseline gut microbial composition (16S <jats:styled-content style="fixed-case">rRNA</jats:styled-content> sequencing) and metabolic capacity (<jats:styled-content style="fixed-case">PICRUS</jats:styled-content>t) were determined. Metagenomic biomarker discovery (<jats:styled-content style="fixed-case">LE</jats:styled-content>fSe) compared Responders (≥50% decrease in abdominal pain frequency on low <jats:styled-content style="fixed-case">FODMAP</jats:styled-content> diet only) vs. Nonresponders (no improvement during either intervention).</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Thirty‐three children completed the study. Less abdominal pain occurred during the low <jats:styled-content style="fixed-case">FODMAP</jats:styled-content> diet vs. <jats:styled-content style="fixed-case">TACD</jats:styled-content> [1.1 ± 0.2 (<jats:styled-content style="fixed-case">SEM</jats:styled-content>) episodes/day vs. 1.7 ± 0.4, <jats:italic>P</jats:italic> < 0.05]. Compared to baseline (1.4 ± 0.2), children had fewer daily abdominal pain episodes during the low <jats:styled-content style="fixed-case">FODMAP</jats:styled-content> diet (<jats:italic>P</jats:italic> < 0.01) but more episodes during the <jats:styled-content style="fixed-case">TACD</jats:styled-content> (<jats:italic>P</jats:italic> < 0.01). Responders were enriched at baseline in taxa with known greater saccharolytic metabolic capacity (e.g. <jats:italic>Bacteroides</jats:italic>,<jats:italic> Ruminococcaceae</jats:italic>,<jats:italic> Faecalibacterium prausnitzii</jats:italic>) and three Kyoto Encyclopedia of Genes and Genomes orthologues, of which two relate to carbohydrate metabolism.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>In childhood <jats:styled-content style="fixed-case">IBS</jats:styled-content>, a low <jats:styled-content style="fixed-case">FODMAP</jats:styled-content> diet decreases abdominal pain frequency. Gut microbiome biomarkers may be associated with low <jats:styled-content style="fixed-case">FODMAP</jats:styled-content> diet efficacy.</jats:p><jats:p><jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="http://ClinicalTrials.gov">ClinicalTrials.gov</jats:ext-link> identifier: <jats:styled-content style="fixed-case">NCT</jats:styled-content>01339117.</jats:p></jats:sec>