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

Respiratory Research, Sep 2016

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-defensin-2 were detected in the bronchoalveolar lavage fluid of male and female mice fed a vitamin D-containing diet. The induction of OVA-induced allergic airway disease itself had a profound affect on the OTUs identified in the lung microbiome, which was accompanied by substantially more respiratory inflammation than that induced by vitamin D deficiency alone. Conclusion These data support the notion that maintaining sufficient vitamin D is necessary for optimal lung health, and that vitamin D may modulate the lung microbiome in a sex-specific fashion. Furthermore, our data suggest that the magnitude of the pro-inflammatory and microbiome-modifying effects of vitamin D deficiency were substantially less than that of allergic airway disease, and that there is an important interplay between respiratory inflammation and the lung microbiome.

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

Roggenbuck et al. Respiratory Research Vitamin D and allergic airway disease shape the murine lung microbiome in a sex- specific manner Michael Roggenbuck 2 Denise Anderson 0 Kenneth Klingenberg Barfod 1 Martin Feelisch 3 Sian Geldenhuys 0 Søren J. Sørensen 2 Clare E. Weeden 0 Prue H. Hart 0 Shelley Gorman 0 0 Telethon Kids Institute, University of Western Australia , 100 Roberts Rd, Subiaco, WA 6008 , Australia 1 The National Research Centre for the Working Environment , Copenhagen , Denmark 2 Section of Microbiology, Department of Biology, University of Copenhagen , Copenhagen , Denmark 3 Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton General Hospital , Southampton , UK 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-defensin-2 were detected in the bronchoalveolar lavage fluid of male and female mice fed a vitamin D-containing diet. The induction of OVAinduced allergic airway disease itself had a profound affect on the OTUs identified in the lung microbiome, which was accompanied by substantially more respiratory inflammation than that induced by vitamin D deficiency alone. Conclusion: These data support the notion that maintaining sufficient vitamin D is necessary for optimal lung health, and that vitamin D may modulate the lung microbiome in a sex-specific fashion. Furthermore, our data suggest that the magnitude of the pro-inflammatory and microbiome-modifying effects of vitamin D deficiency were substantially less than that of allergic airway disease, and that there is an important interplay between respiratory inflammation and the lung microbiome. Vitamin D; Lung; Allergic airway disease; Inflammation; Microbiome; Sex differences; Acinetobacter Background Vitamin D has been proposed as an important regulator of both inflammation [ 1 ] and the microbiome [ 2, 3 ]. Indeed, it is hypothesised that there is a protective role for vitamin D in regulating the gut microbiome, which may shape predisposition for the development of inflammatory autoimmune and allergic diseases [ 2–4 ]. Vitamin D is commonly acquired through skin exposure to ultraviolet B radiation found in sunlight and through the diet. Circulating 25-hydroxyvitamin D (25(OH)D) is typically used as a measure of vitamin D status, although 1,25dihydroxyvitamin D (1,25(OH)2D) is the most active vitamin D metabolite. Our understanding of the effects of vitamin D on the microbiome and its associations with reduced tissue inflammation is currently limited to the gastrointestinal tract. Colitis severity and bacterial numbers in the colons of mice were increased during vitamin D deficiency [ 5 ]. Dietary-induced vitamin D deficiency altered the composition of the fecal microbiome of C57Bl/6 mice, which had increased relative quantities of Bacteroidetes, Firmicutes, Actinobacteria, and Gammaproteobacteria [ 6 ]. These mice also had increased colonic injury in comparison to mice fed a vitamin D-sufficient diet, but exhibited signs of hypocalcemia [ (...truncated)


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Michael Roggenbuck, Denise Anderson, Kenneth Barfod, Martin Feelisch, Sian Geldenhuys, Søren Sørensen, Clare Weeden, Prue Hart, Shelley Gorman. Vitamin D and allergic airway disease shape the murine lung microbiome in a sex-specific manner, Respiratory Research, 2016, pp. 116, 17, DOI: 10.1186/s12931-016-0435-3