Altered fecal microbiota composition associated with food allergy in infants

Abstract

Increasing evidence suggests that perturbations in the intestinal microbiota composition of infants are implicated in the pathogenesis of food allergy (FA), while the actual structure and composition of the intestinal microbiota in human beings with FA remain unclear. Microbial diversity and composition were analyzed with parallel barcoded 454 pyrosequencing targeting the 16S rRNA gene hypervariable V1-V3 regions in the feces of 34 infants with FA (17 IgE mediated and 17 non-IgE mediated) and 45 healthy controls. Here, we showed that several key FA-associated bacterial phylotypes, but not the overall microbiota diversity, significantly changed in infancy fecal microbiota with FA and were associated with the development of FA. The proportion of abundant Bacteroidetes, Proteobacteria, and Actinobacteria phyla were significantly reduced, while the Firmicutes phylum was highly enriched in the FA group (P < 0.05). Abundant Clostridiaceae 1 organisms were prevalent in infants with FA at the family level (P = 0.016). FA-enriched phylotypes negatively correlated with interleukin-10, for example, the genera Enterococcus and Staphylococcus. Despite profound interindividual variability, levels of 20 predominant genera were significantly different between the FA and healthy control groups (P < 0.05). Infants with IgE-mediated FA had increased levels of Clostridium sensu stricto and Anaerobacter and decreased levels of Bacteroides and Clostridium XVIII (P < 0.05). A positive correlation was observed between Clostridium sensu stricto and serum-specific IgE (R = 0.655, P < 0.001). The specific microbiota signature could distinguish infants with IgE-mediated FA from non-IgE-mediated ones. Detailed microbiota analysis of a well-characterized cohort of infants with FA showed that dysbiosis of fecal microbiota with several FA-associated key phylotypes may play a pathogenic role in FA.

FIG 1

Comparison of relative abundance at the bacterial family level between infants with food allergy and healthy controls. (A) Asterisks indicate P < 0.05. Correlation between interleukin-10 and the relative abundance of the genera Enterococcus (B) and Staphylococcus (C). The Spearman rank correlation (R) and probability (P) were used to evaluate statistical importance. (D) Linear discriminant analysis (LDA) coupled with effect size measurements identifies the most differentially abundant taxons between infants with food allergy and healthy controls. Healthy control-enriched taxa are indicated with a positive LDA score (green), and taxa enriched in food allergy have a negative score (red). Only taxa meeting an LDA significant threshold of >2 are shown. (E) A cladogram representation of data shown in panel A. Red, food allergy-enriched taxa; green, taxa enriched in healthy controls. The brightness of each dot is proportional to its effect size.

FIG 2

LEfSe identifies the most differentially abundant taxons between IgE-mediated food allergy infants and non-IgE-mediated food allergy ones. Non-IgE-mediated food allergy-enriched taxa are indicated with a positive LDA score (green), and taxa enriched in IgE-mediated food allergy have a negative score (red). (A) Only taxa meeting an LDA significant threshold of >2 are shown. (B) A cladogram representation of data shown in panel A. Red, IgE-mediated food allergy-enriched taxa; green, taxa enriched in non-IgE-mediated food allergy infants. The brightness of each dot is proportional to its effect size. (C) The relative abundance of different genera obtained in fecal microbiota from IgE-mediated and non-IgE-mediated food allergy infants. The Mann-Whitney test was used to evaluate the two groups. *, P < 0.05; **, P < 0.01. (D) Correlation between specific serum IgE and the relative abundance of Clostridium sensu stricto. The Spearman rank correlation (R) and probability (P) were used to evaluate statistical importance. KU/L, kilo-international units per liter.