Impact of high-dose cholecalciferol (vitamin D3) and inulin prebiotic on intestinal and airway microbiota in adults with cystic fibrosis: A 2 × 2 randomized, placebo-controlled, double-blind pilot study

• Type of Material: Article
• Authors: Pichatorn Suppakitjanusant, Emory University; Yanling Wang, Georgia State University; Alisa K. Sivapiromrat, Emory University; Chengcheng Hu, Emory University; Jose Binongo, Emory University; William R. Hunt, Emory University; Samuel Weinstein, Emory University; Ishaan Jathal, Emory University; Jessica A. Alvarez, Emory University; Benoit Chassaing, Université Paris Cité; Thomas ziegler, Emory University; Andrew T. Gewirtz, Georgia State University; Vin Tangpricha, Emory University
• Language: English
• Date: 2024
• Publisher: Elsevier
• Publication Version: Final Published Version
• Copyright Statement: © 2024 Elsevier B.V., its licensors, and contributors. All rights are reserved, including those for text and data mining, AI training, and similar technologies.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): https://www.sciencedirect.com/science/article/pii/S2214623724000334
• Title of Journal or Parent Work: Journal of Clinical & Translational Endocrinology
• Volume: 37
• Start Page: 100362
• Grant/Funding Information: This study was supported by Cystic Fibrosis Foundation Awards TANGPR19A0 and CC002-AD (United States) and NIH awards P30DK125013 and 3UL1TR002378-05S2 (United States).
• Keywords: Vitamin D; Cholecalciferol; Cystic fibrosis; Prebiotics; Inulin; Microbiome; vitamin D deficiency
• Research Categories: Health Sciences, Nutrition

Abstract

Background Cystic fibrosis (CF) is a multi-organ disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). Individuals with CF often have gastrointestinal (GI) dysbiosis due to chronic inflammation and antibiotic use. Previous studies suggested a role for vitamin D in reversing the GI dysbiosis found in CF. Objective To explore the potential role of a combination of high-dose oral cholecalciferol (vitamin D3) and fermentable dietary fiber, inulin, to impact bacterial composition, richness, and diversity of intestinal and airway microbiota in adults with CF. Methods This was a 2 × 2 factorial, double-blinded, placebo-controlled, randomized, pilot clinical trial in which adults with CF received oral cholecalciferol (vitamin D3) (50,000 IU/week) and/or inulin (12 g/day) for 12 weeks. Thus, there were 4 study groups (n = 10 subjects per group); 1) placebo 2) vitamin D3 3) inulin 4) vitamin D3 plus inulin. Stool and sputum samples were collected at baseline (just before) and after the intervention and were analysed using 16S ribosomal RNA gene sequencing for gut and airway microbiota composition. Statistical analyses assessed alpha and beta diversity to evaluate microbial community changes. Results Of a total of 254 screened participants, 40 eligible participants were randomized to one of the 4 treatment arms. Participants receiving vitamin D3 plus inulin exhibited greater changes in microbiome indexes in both intestinal and airway relative to those in the other study groups. Specific taxonomic changes supported the potential beneficial influence of this combination to mitigate both intestinal and airway dysbiosis in adults with CF. Conclusion This pilot study established that the combination of oral vitamin D3 and the prebiotic inulin was well tolerated over 12 weeks in adults with CF and altered gut and airway bacterial communities. Future research appear warranted to define clinical outcomes and the role of microbiota changes therein with this approach.