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Depner, M. ; Taft, D.H.* ; Kirjavainen, P.V.* ; Kalanetra, K.M.* ; Karvonen, A.M.* ; Peschel, S. ; Schmaußer-Hechfellner, E. ; Roduit, C.* ; Frei, R.* ; Lauener, R.* ; Divaret-Chauveau, A.* ; Dalphin, J.C.* ; Riedler, J.* ; Roponen, M.* ; Kabesch, M.* ; Renz, H.* ; Pekkanen, J.* ; Farquharson, F.M.* ; Louis, P.* ; Mills, D.A.* ; PASTURE Study Group (Illi, S. ; von Mutius, E.) ; Ege, M.J.*

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

Nat. Med. 26, 1766-1775 (2020)

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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 (beta = 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.Growing up in the rich microbial environment of a farm strongly influences the maturation of the gut microbiome in the first year of life, which helps protect against the development of asthma in children.

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