Bolus Weekly Vitamin D3 Supplementation Impacts Gut and Airway Microbiota in Adults With Cystic Fibrosis: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial

J Clin Endocrinol Metab. 2018 Feb 1;103(2):564-574. doi: 10.1210/jc.2017-01983.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cholecalciferol / administration & dosage*
  • Cystic Fibrosis / complications
  • Cystic Fibrosis / diet therapy*
  • Cystic Fibrosis / microbiology
  • Dietary Supplements
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Gastrointestinal Microbiome / drug effects*
  • Humans
  • Male
  • Microbiota / drug effects*
  • Middle Aged
  • Pilot Projects
  • Respiratory System / drug effects*
  • Respiratory System / microbiology*
  • Vitamin D Deficiency / complications
  • Vitamin D Deficiency / diet therapy*
  • Vitamin D Deficiency / microbiology
  • Young Adult

Substances

  • Cholecalciferol

Associated data

  • ClinicalTrials.gov/NCT02589444