Gut microbiota influences low fermentable substrate diet efficacy in children with irritable bowel syndrome

Abstract

We sought to determine whether a low fermentable substrate diet (LFSD) decreases abdominal pain frequency in children with irritable bowel syndrome (IBS) and to identify potential microbial factors related to diet efficacy. Pain symptoms, stooling characteristics, breath hydrogen and methane, whole intestinal transit time, stool microbiome, and metabolite composition were collected and/or documented in eight children with IBS at baseline and during one week of an LFSD intervention. Pain frequency (P<0.05), pain severity (P<0.05), and pain-related interference with activities (P<0.05) decreased in the subjects while on the LFSD. Responders vs. non-responders: four children (50%) were identified as responders (> 50% decrease in abdominal pain frequency while on the LFSD). There were no differences between responders and non-responders with respect to hydrogen production, methane production, stooling characteristics, or gut transit time. Responders were characterized by increased pre-LFSD abundance of bacterial taxa belonging to the genera Sporobacter (P<0.05) and Subdoligranulum (P<0.02) and decreased abundance of taxa belonging to Bacteroides (P<0.05) relative to non-responders. In parallel, stool metabolites differed between responders and non-responders and were associated with differences in microbiome composition. These pilot study results suggest that an LFSD may be effective in decreasing GI symptoms in children with IBS. Microbial factors such as gut microbiome composition and stool metabolites while on the diet may relate to LFSD efficacy.

Keywords: FODMAPs; abdominal pain; irritable bowel syndrome; metabolites; microbiome; pediatric.

Figures

Figure 1. Trial flow sheet. LFSD, low fermentable substrate diet.

Figure 2. The gut microbiome (family-level) at baseline and during the low fermentable substrate diet by relative abundance. LFSD, low fermentable substrate diet.

Figure 3. (A) LEfSe analysis differences of baseline microbial composition between responders and non-responders at the OTU level. Positive linear discriminant analysis (LDA) scores represent OTUs that were enriched in responders, while negative LDA scores indicate OTUs that were enriched in non-responders. (B) Microbiomes of children with IBS who are responders segregate from that of non-responders to a low fermentable substrate diet. A partial responder (reduction in pain frequency >30% but not 50%) is identified. (C) Responder vs. non-responder segregation is particularly seen when only comparing those with IBS with constipation (IBS-C) predominance.

Figure 4. LEfSe analysis of differences in microbial composition during the low fermentable substrate diet between responders and non-responders at the OTU level. Positive linear discriminant analysis (LDA) scores represent OTUs that were enriched in responders, while negative LDA scores indicate OTUs that were enriched in non-responders.

Figure 5. Hive plot showing tripartite associations among microbial taxa, metabolites, and clinical response following a low fermentable substrate dietary intervention. Responders were defined as those with a ≥50% decrease in abdominal pain frequency during the intervention. Red lines indicate a negative correlation (OTU vs. metabolite) or relative depletion (OTU or metabolite vs. subjects), while black lines indicate positive correlations or enrichment. OTUs and metabolites are color coded by taxonomic affiliation or metabolite class, and OTUs and metabolites of specific interest are highlighted with labels. Positive correlations are shown with respect to subject correlations though the inverse (negative correlation) is present in the other subject group (responders vs. non-responders).