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 gut microbiota may exacerbate severity of cystic fibrosis (CF). Vitamin D deficiency 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 vitamin D3 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 vitamin D sufficient (n = 18). Subjects with vitamin D insufficiency were randomized to receive 50,000 IU of oral vitamin D3 or placebo weekly for 12 weeks. Sputum and 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 D-insufficient patients following 12 weeks treatment with placebo or vitamin D3 (permutation multivariate 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.

Trial registration: ClinicalTrials.gov NCT02589444.

Copyright © 2017 Endocrine Society

Figures

Figure 1.

CONSORT diagram showing recruitment and allocation of subjects. IBD, inflammatory bowel disease.

Figure 2.

Mean serum 25(OH)D in response to weekly vitamin D3 treatment or placebo in adults with CF and vitamin D insufficiency. Means with standard error bars of serum 25(OH)D concentrations between the placebo group (red; n = 10) and treatment group (blue; n = 10) at baseline and final visit at 12 weeks. Subjects who were randomized to oral vitamin D3 50,000 IU had higher serum 25(OH)D concentrations compared with the subjects randomized to placebo [P = 0.02 (β = 16.81)], and this remained significant when adjusted by baseline serum 25(OH)D (β = 17.08, P = 0.03).

Figure 3.

Differentially abundant taxa, according to vitamin D status of the subject at baseline. (A) LEfSE showing genera and species that were significantly altered in the stool samples of vitamin D-sufficient subjects (red) compared with vitamin D-insufficient subjects (green) at baseline. (B) Potentially pathogenic taxa belonging to the class Gammaproteobacteria were significantly more abundant in the stool samples of vitamin D-insufficient subjects compared with vitamin D-sufficient subjects at baseline (LDA score = 4.96).

Figure 4.

Principal coordinate (PC) analysis based on unweighted UniFrac distance matrices generated with stool 16S rRNA gene sequencing. Stool samples from adults with CF and vitamin D insufficiency [25(OH)D 3 (blue) were analyzed at (A) baseline and (B) the end of 12 weeks of intervention of weekly 50,000 IU of vitamin D3.

Figure 5.

Differentially abundant taxa in vitamin D-insufficient, randomized subjects based on treatment assignment. LEfSE showing genera and species substantially, differentially abundant in the stool samples from adults with CF and vitamin D insufficiency [25(OH)D 3 (green).