Bolus weekly Vitamin D3 supplementation impacts gut and airway microbiota in adults with cystic fibrosis: A double-blind, randomized, placebo-controlled clinical trial

Abstract

Context: Disruption of gutmicrobiotamay exacerbate severity of cystic fibrosis (CF). VitaminDdeficiency is a common comorbidity in patients with CF that may influence composition of the gut microbiota. Objectives: Compare microbiota of Vitamin D-sufficient and -insufficient CF patients and assess impact of a weekly high-dose vitaminD3 bolus regimen on gut and airway microbiome in adults with CF and Vitamin D insufficiency (25-hydroxyVitamin D < 30 ng/mL). Design: Forty-one subjects with CF were classified into two groups: Vitamin D insufficient (n = 23) and vitaminDsufficient (n = 18). Subjectswith vitaminDinsufficiencywere randomizedto receive 50,000 IU of oral Vitamin D3 or placebo weekly for 12 weeks. Sputumand stool samples were obtained pre-And postintervention and 16S ribosomal RNA genes sequenced using Illumina MiSeq technology. Results: Gut microbiota differed significantly based on Vitamin D status with Gammaproteobacteria, which contain numerous, potentially pathogenic species enriched in the Vitamin D-insufficient group. Principal coordinates analysis showed differential gut microbiota composition within the Vitamin Dinsufficient patients following 12 weeks treatment with placebo or vitaminD3 (permutationmultivariate analysis of variance = 0.024), with Lactococcus significantly enriched in subjects treated with Vitamin D3, whereas Veillonella and Erysipelotrichaceae were significantly enriched in patients treated with placebo. Conclusion: This exploratory study suggests that Vitamin D insufficiency is associated with alterations in microbiota composition that may promote inflammation and that supplementation with Vitamin D has the potential to impact microbiota composition. Additional studies to determine the impact of Vitamin D on microbiota benefit clinical outcomes in CF are warranted.