Gut Microbiome Biomarkers Are Associated With Clinical Response to a Low FODMAP Diet in Children With the Irritable Bowel Syndrome

Randomised Clinical Trial

B. P. Chumpitazi; J. L. Cope; E. B. Hollister; C. M. Tsai; A. R. McMeans; R. A. Luna; J. Versalovic; R. J. Shulman

Disclosures

Aliment Pharmacol Ther. 2015;42(4):418-427. 

In This Article

Abstract and Introduction

Abstract

Background A low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet can ameliorate symptoms in adult irritable bowel syndrome (IBS) within 48 h.

Aim To determine the efficacy of a low FODMAP diet in childhood IBS and whether gut microbial composition and/or metabolic capacity are associated with its efficacy.

Methods In a double-blind, crossover trial, children with Rome III IBS completed a 1-week baseline period. They then were randomised to a low FODMAP diet or typical American childhood diet (TACD), followed by a 5-day washout period before crossing over to the other diet. GI symptoms were assessed with abdominal pain frequency being the primary outcome. Baseline gut microbial composition (16S rRNA sequencing) and metabolic capacity (PICRUSt) were determined. Metagenomic biomarker discovery (LEfSe) compared Responders (≥50% decrease in abdominal pain frequency on low FODMAP diet only) vs. Nonresponders (no improvement during either intervention).

Results Thirty-three children completed the study. Less abdominal pain occurred during the low FODMAP diet vs. TACD [1.1 ± 0.2 (SEM) episodes/day vs. 1.7 ± 0.4, P < 0.05]. Compared to baseline (1.4 ± 0.2), children had fewer daily abdominal pain episodes during the low FODMAP diet (P < 0.01) but more episodes during the TACD (P < 0.01). Responders were enriched at baseline in taxa with known greater saccharolytic metabolic capacity (e.g. Bacteroides,Ruminococcaceae,Faecalibacterium prausnitzii) and three Kyoto Encyclopedia of Genes and Genomes orthologues, of which two relate to carbohydrate metabolism.

Conclusions In childhood IBS, a low FODMAP diet decreases abdominal pain frequency. Gut microbiome biomarkers may be associated with low FODMAP diet efficacy. ClinicalTrials.gov identifier: NCT01339117.

Introduction

Childhood irritable bowel syndrome (IBS) is a common functional gastrointestinal (GI) disorder affecting up to 20% of school-aged children and characterised by abdominal discomfort associated with defecation, or changes in stool frequency or stool form.[1] Children with functional GI disorders frequently attribute some of their symptoms to specific foods, which negatively affect their quality of life.[2]

Fermentable carbohydrates such as lactose and fructose may be difficult to absorb and have been blamed for causing symptoms in children with chronic abdominal pain.[3] The onset of these symptoms may be rapid, with an increase in GI symptoms in lactose intolerant adults with IBS occurring within 3 h following a lactose challenge.[4] The potential role of fermentable carbohydrates becomes more intriguing given their ever increasing consumption in the typical American childhood diet (TACD).[5] However, controlled carbohydrate restriction dietary intervention trials in children with IBS have not demonstrated clear efficacy to date but primarily have focused on the restriction of only one (e.g. lactose) substrate at a time.[6] Recently, the low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) diet, which comprehensively lowers the intake of several fermentable carbohydrates concurrently, has been shown to decrease GI symptoms in adults with IBS.[7] The length of time needed for GI symptom amelioration on a low FODMAP diet in adult IBS is as little as 48 h.[8] A randomised controlled trial of a low FODMAP diet has not been conducted to date in children with IBS.

Despite the evidence supporting low FODMAP diet efficacy, ≥25% of adult IBS subjects do not improve on the diet.[9] Although compliance may contribute to low FODMAP efficacy,[10] there is little information regarding other factors which may play a role. The hypothesised mechanism of action of a low FODMAP diet is related to decreased microbial fermentation of dietary carbohydrate leading to lower luminal osmolality and gas (e.g. hydrogen) generation.[11] Several adult IBS studies have reported changes in specific stool bacterial composition while on the low FODMAP diet.[12,13] However, none of the studies have determined whether baseline gut microbiome composition may relate to low FODMAP diet efficacy or have completed comprehensive metagenomic evaluations of gut microbiome composition. Being able to predict who will respond to a low FODMAP diet may help avoid beginning this relatively challenging diet in those unlikely to respond.[14]

In a small, open label, pilot study, we previously demonstrated the potential benefit of a low FODMAP diet in children with IBS.[15] Those who responded robustly to the diet were found to have a different microbiome composition as compared to those who did not. Given these results, in a separate group of children, we carried out a randomised, double-blind, crossover trial to determine the effectiveness of a low FODMAP diet in childhood IBS. We hypothesised that a low FODMAP diet would decrease abdominal pain frequency and that children who responded to the diet would have a different microbiome composition and associated microbial metabolic capacity as compared to those who did not respond.

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....