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Delayed gut microbiota maturation in the first year of life is a hallmark of pediatric allergic disease.

Courtney HoskinsonDarlene L Y DaiKate L Del BelAllan B BeckerTheo J MoraesPiushkumar J MandhaneB Brett FinlayElinor SimonsAnita L KozyrskyjMeghan B AzadPadmaja SubbaraoCharisse PetersenStuart E Turvey
Published in: Nature communications (2023)
Allergic diseases affect millions of people worldwide. An increase in their prevalence has been associated with alterations in the gut microbiome, i.e., the microorganisms and their genes within the gastrointestinal tract. Maturation of the infant immune system and gut microbiota occur in parallel; thus, the conformation of the microbiome may determine if tolerant immune programming arises within the infant. Here we show, using deeply phenotyped participants in the CHILD birth cohort (n = 1115), that there are early-life influences and microbiome features which are uniformly associated with four distinct allergic diagnoses at 5 years: atopic dermatitis (AD, n = 367), asthma (As, n = 165), food allergy (FA, n = 136), and allergic rhinitis (AR, n = 187). In a subset with shotgun metagenomic and metabolomic profiling (n = 589), we discover that impaired 1-year microbiota maturation may be universal to pediatric allergies (AD p = 0.000014; As p = 0.0073; FA p = 0.00083; and AR p = 0.0021). Extending this, we find a core set of functional and metabolic imbalances characterized by compromised mucous integrity, elevated oxidative activity, decreased secondary fermentation, and elevated trace amines, to be a significant mediator between microbiota maturation at age 1 year and allergic diagnoses at age 5 years (β indirect  = -2.28; p = 0.0020). Microbiota maturation thus provides a focal point to identify deviations from normative development to predict and prevent allergic disease.
Keyphrases
  • allergic rhinitis
  • atopic dermatitis
  • early life
  • mental health
  • single cell
  • genome wide
  • young adults
  • dna methylation
  • cystic fibrosis
  • transcription factor
  • air pollution