Maturation of the gut microbiome during the first year of life contributes to the protective farm effect on childhood asthma.
Depner Martin, Taft Diana Hazard, Kirjavainen Pirkka V, Kalanetra Karen M, Karvonen Anne M, Peschel Stefanie, Schmausser-Hechfellner Elisabeth, Roduit Caroline, Frei Remo, Lauener Roger, Divaret-Chauveau Amandine, Dalphin Jean-Charles, Riedler Josef, Roponen Marjut, Kabesch Michael, Renz Harald, Pekkanen Juha, Farquharson Freda M, Louis Petra, Mills David A, von Mutius Erika, PASTURE study group, Ege Markus J
Nature medicine · 2020 · PMID 33139948 · 인용 372
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.