2026-07-28 ミュンヘン大学（LMU）
＜関連情報＞
- https://www.lmu.de/en/newsroom/news-overview/news/immune-system-the-farm-effect-clearer-than-ever-de3abdfb.html
- https://evidence.nejm.org/doi/full/10.1056/EVIDoa2500271
グラム陽性菌と、農場での曝露と小児喘息との逆相関関係 Gram-Positive Bacteria and the Inverse Association between Farm Exposure and Childhood Asthma
Giulia Pagani, Ph.D., Georg Loss, Ph.D., Sonali Pechlivanis, Ph.D., Martin Depner, Ph.D., Constanze Müller, Ph.D., Jinlong Ru, Ph.D., Christine Strunz-Lehner, M.P.H., +16 , for the GABRIELA and PASTURE study groups
NEJM Evidence Published: July 28, 2026
DOI: 10.1056/EVIDoa2500271
Abstract
Background
The inverse association of farm exposure with asthma and atopic conditions has been attributed to the diversity of environmental bacteria and fungi, but the specific taxa and the underlying mechanisms remain elusive.
Methods
We performed sequencing of the bacterial 16S ribosomal ribonucleic acid (16S rRNA) gene in mattress dust samples from 1018 schoolchildren from two German populations of the cross-sectional GABRIELA (Multidisciplinary Study to Identify the Genetic and Environmental Causes of Asthma in the European Community [GABRIEL] Advanced Study) survey. Bacterial metabolic pathways and enzymes were assessed bioinformatically, and metabolites were measured by using mass spectrometry. Statistical methods included network, interaction, and mediation analyses.
Results
Within the highly diverse microbial exposure in a farm environment, the study identified nine gram-positive environmental bacterial genera, whose composite score explained two thirds of the inverse association of farm exposure and asthma in a mediation analysis. The effect was independent of gram-negative farm-associated bacteria. A PICRUSt2 (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) analysis revealed nine pathways, whose enzymes were encoded by the identified genera and whose metabolites were detected in cowshed dust by using mass spectrometry. The metabolites included ligands of the human aryl hydrocarbon receptor (kynurenine and xanthine) and the peroxisome proliferator-activated receptor-γ (α-linoleic and stearidonic acid). Single nucleotide polymorphisms of the corresponding human receptor genes interacted with the composite score of the bacterial genera for asthma. Fungi and bacteriophages co-occurred with the beneficial bacteria but did not carry the protective effect. All results were replicated in independent populations.
Conclusions
In this analysis, the inverse association of childhood asthma and farm exposure was largely mediated by exposure to gram-positive bacterial genera. Gene–environment interactions of a compound score of these bacteria with human receptors recognizing bacterial metabolites suggest novel approaches to asthma prevention.
