Lung microbial dysbiosis during early life promotes predisposition to allergic asthma.

Abstract

Abstract Background: Allergic asthma is associated with lung microbial dysbiosis. We hypothesized that the microbiome from the lungs of allergy-predisposed mouse pups is sufficient to predispose pups to development of allergy. Allergic inflammation in pups of allergic dams is blocked by α-tocopherol supplementation of the dam during gestation and nursing, but it is unknown whether α-tocopherol alters microbial composition of the lung. Methodology: Mouse pups were predisposed to allergy by inducing allergy in the mothers. Microbiome was separated from the bronchoalveolar lavage (BAL) of pups of allergic and non-allergic mothers and transferred intranasally at postnatal day 4. 16S rRNA sequencing was performed on the Illumina MiSeq platform. Results: Compared to pups born to non-allergic dams and dams administered with a-tocopherol supplementation, mouse pups born to allergic dams had elevated abundance of several genera of the γ-Proteobacteria, Firmicutes, and Verrucomicrobia (p<0.05). There was decreased abundance of genera from Bacteroides, Firmicutes, and α-Proteobacteria (p<0.05). Transfer of lung microbiome from neonates of allergic dams to neonates of non-allergic dams was sufficient to confer responsiveness to allergen in the recipient pups. Neonates of allergic dams were not protected from development of allergy by transfer of donor lung microbiome from neonates of non-allergic dams or neonates of αT-supplemented allergic dams. The donor microbiome from pups of allergic mothers colonized the pup lung, suggesting that early life detrimental bacterial species persists. Conclusion: The lung microbiome from allergy-predisposed pups is dominant and sufficient for enhanced neonate responsiveness to allergen. Supported by grants from NIH (R01AI127695)