Maturation of the gut microbiome during the first year of life contributes to the protective farm effect on childhood asthma

Martin Depner, Diana Hazard Taft, Pirkka V. Kirjavainen, Karen M. Kalanetra, Anne M. Karvonen, Stefanie Peschel, Elisabeth Schmausser-Hechfellner, Caroline Roduit, Remo Frei, Roger Lauener, Amandine Divaret-Chauveau, Jean-Charles Dalphin, Josef Riedler, Marjut Roponen, Michael Kabesch, Harald Renz, Juha Pekkanen, Freda Farquharson, Petra Louis, David MillsErika von Mutius, Markus J Ege

Research output: Contribution to journalArticle

Abstract

Growing up on a farm is associated with an asthma-protective effect, but the mechanisms underlying this effect are largely unknown. In the Protection against Allergy: Study in Rural Environments (PASTURE) birth cohort, we modeled maturation using 16S rRNA sequence data of the human gut microbiome in infants from 2 to 12 months of age. The estimated microbiome age (EMA) in 12-month-old infants was associated with previous farm exposure (β = 0.27 (0.12–0.43), P = 0.001, n = 618) and reduced risk of asthma at school age (odds ratio (OR) = 0.72 (0.56–0.93), P = 0.011). EMA mediated the protective farm effect by 19%. In a nested case–control sample (n = 138), we found inverse associations of asthma with the measured level of fecal butyrate (OR = 0.28 (0.09–0.91), P = 0.034), bacterial taxa that predict butyrate production (OR = 0.38 (0.17–0.84), P = 0.017) and the relative abundance of the gene encoding butyryl–coenzyme A (CoA):acetate–CoA-transferase, a major enzyme in butyrate metabolism (OR = 0.43 (0.19–0.97), P = 0.042). The gut microbiome may contribute to asthma protection through metabolites, supporting the concept of a gut–lung axis in humans.

Original languageEnglish
Pages (from-to)1766-1775
Number of pages10
JournalNature Medicine
Volume26
Issue number11
Early online date2 Nov 2020
DOIs
Publication statusPublished - Nov 2020

Keywords

  • asthma
  • epidemiology
  • microbiome
  • paediatrics
  • BACTERIA
  • ENVIRONMENTS
  • VARIANTS
  • SUSCEPTIBILITY
  • RISK
  • COLONIZATION
  • POLYMORPHISMS
  • DIVERSITY
  • ASSOCIATION
  • ATOPY

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