Maternal ß-glucosylceramides alter neonate lung microbiota and lung allergic inflammation.

Allergic asthma is associated with lung microbial dysbiosis. ß-glucosylceramides (ßGlcCers) are lipids elevated in the serum of allergic mothers and are necessary and sufficient for allergen hyperresponsiveness in neonates. When we transfer lung microbiota from pups born to allergic mothers, allergen hypersensitivity was induced in recipient neonates. The mechanism of lung microbial dysbiosis in neonates is unknown. Since maternal ßGlcCers cross the placenta, we hypothesized that maternal ßGlcCers are sufficient to alter the pup lung microbiota. Pregnant mice received subcutaneous injections of ßGlcCers daily during gestation and nursing. Mother and pup lung microbiota were analyzed via 16S sequencing. PCA of maternal BAL microbiota revealed distinct clustering between mothers injected with ßGlcCers and vehicle control. Mothers injected with ßGlcCers had BAL enriched with the class-level clades Verrucomicrobiae, Gammaproteobacteria, Erysipelotrichia and Clostridia as compared mothers injected with vehicle control. Within distinct clusters of microbiota, pups born to mothers injected with ßGlcCers were enriched with Coriobacteria while pups born to control mothers were enriched with Bacteroidia. In conclusion, maternal ßGlcCers altered the lung microbiota in both mothers and pups. Ongoing analysis employs metabolic modeling to determine the capacity of the lung microbiota to convert ßGlcCers.