Does an unbalanced microbiota at age one lead to allergies at age five?
Delayed maturation of the gut microbiota in early childhood appears to be a universal sign of subsequent allergy development. Could the metabolites involved serve as markers for these allergies or even help prevent them?
About this article
Asthma, allergic rhinitis, food allergies, and atopic dermatitis are often studied on their own, despite having many similar mechanisms (inflammatory responses, immunoglobulin E). Could something else they have in common be the gut microbiota, which matures in parallel with the infant immune system? To find out, data from 1,115 children included in the vast (sidenote: https://childstudy.ca/ ) longitudinal study were used: 592 children diagnosed with one or more allergic disorders after the age of 5, and 523 children with no signs of allergic sensitization. Regression analysis revealed several risk factors, such as male gender, paternal or maternal history, and antibiotic use before the age of one. Breastfeeding up to six months of age and Caucasian ethnicity appear to be protective.
Less mature gut microbiota
An analysis of stool samples collected at three months and one year of age revealed a delay in microbiota diversification in the children who subsequently developed allergies. Whereas control children had age-appropriate gut flora at age one, future allergic children showed a delay in the maturation of their microbiota. Less maturation of the microbiota at age one seems to be associated with an increased risk of allergic disorders at age five, regardless of the allergy.
Gut microbiota dysbiosis
A gut dysbiosis at age one also characterizes future allergic children: depleted levels of four bacterial species that produce short-chain fatty acids (butyrate-producing Anaerostipes hadrus, Fusicatenibacter saccharivorans and Eubacterium hallii, and acetate-producing Blautia wexlerae) and an increased abundance of five bacteria generally considered pathogenic (Eggerthella lenta, Escherichia coli, Enterococcus faecalis, Clostridium innocuum, and Tyzzerella nexilis). Enrichment in C. innocuum and T. nexilis is correlated with antibiotic use; the abundance of C. innocuum, E. lenta, E. faecalis, and T. nexilis depends on whether or not the baby is breast-fed at six months; while the abundance of C. innocuum and E. lenta is correlated with paternal atopy, and so on.
Metabolites to predict or prevent?
In parallel, the researchers identified 11 metabolic pathways significantly altered in at least two of the allergy diagnoses: nine deleterious pathways correlated mainly with E. coli, while two protective pathways were linked to the bacteria B. wexlerae, F. saccharivorans, A. hadrus, and E. hallii.
A metabolite analysis led to associations with age predicted by the gut microbiota: elevated trace amines (phenylethylamine, tryptamine, and tyramine) promoted inflammation and reduced butyrate production. Thus, the association between altered microbiota maturation and allergies at age five appears to be mediated by these metabolites, which may represent first-choice targets for predicting and/or preventing the development of pediatric allergies.