Vitamin D and allergic airway disease shape the murine lung microbiome in a sex-specific manner

© 2016 The Author(s).Background: Vitamin D is under scrutiny as a potential regulator of the development of respiratory diseases characterised by chronic lung inflammation, including asthma and chronic obstructive pulmonary disease. It has anti-inflammatory effects; however, knowledge around the relationship between dietary vitamin D, inflammation and the microbiome in the lungs is limited. In our previous studies, we observed more inflammatory cells in the bronchoalveolar lavage fluid and increased bacterial load in the lungs of vitamin D-deficient male mice with allergic airway disease, suggesting that vitamin D might modulate the lung microbiome. In the current study, we examined in more depth the effects of vitamin D deficiency initiated early in life, and subsequent supplementation with dietary vitamin D on the composition of the lung microbiome and the extent of respiratory inflammation. Methods: BALB/c dams were fed a vitamin D-supplemented or -deficient diet throughout gestation and lactation, with offspring continued on this diet post-natally. Some initially deficient offspring were fed a supplemented diet from 8 weeks of age. The lungs of naïve adult male and female offspring were compared prior to the induction of allergic airway disease. In further experiments, offspring were sensitised and boosted with the experimental allergen, ovalbumin (OVA), and T helper type 2-skewing adjuvant, aluminium hydroxide, followed by a single respiratory challenge with OVA. Results: In mice fed a vitamin D-containing diet throughout life, a sex difference in the lung microbial community was observed, with increased levels of an Acinetobacter operational taxonomic unit (OTU) in female lungs compared to male lungs. This effect was not observed in vitamin D-deficient mice or initially deficient mice supplemented with vitamin D from early adulthood. In addition, serum 25-hydroxyvitamin D levels inversely correlated with total bacterial OTUs, and Pseudomonas OTUs in the lungs. Increased levels of the antimicrobial murine ß-