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, and Ege, Markus J.
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 (ß?=?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.