Journal
NATURE MEDICINE
Volume 26, Issue 11, Pages 1766-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41591-020-1095-x
Keywords
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Funding
- European Commission [QLK4-CT-2001-00250, FOOD-CT-2006-31708, KBBE-2007-2-2-06]
- European Research Council [250268]
- German Federal Ministry of Education and Research (BMBF
- project German Center for Lung Research (DZL))
- Scottish Government's Rural and Environment Sciences and Analytical Services Division (RESAS)
- European Research Council (ERC) [250268] Funding Source: European Research Council (ERC)
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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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