Effect of Vitamin D Supplementation on Human Gut Microbiota: A Systematic Review of Randomized Controlled Trials

Abstract

Context: Studies findings have suggested that vitamin D plays a critical role in maintaining overall health, including having a potential impact on gut microbiota composition, which influences various physiological processes.

Objectives: To examine the effects of vitamin D supplementation on human gut microbiota composition and diversity by analyzing findings from randomized controlled trials (RCTs).

Data sources: A comprehensive search of the MEDLINE, Web of Science, Scopus, and the Cochrane Library electronic databases was conducted to identify relevant studies published from January 1, 2015, to November 30, 2024. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement was followed.

Data extraction: Inclusion criteria were RCTs investigating the impact of vitamin D supplementation on gut microbiota, with outcomes measured using high-throughput sequencing techniques. This review included 14 RCTs encompassing a total of 1458 participants of varying health status and supplementation regimens.

Data analysis: Findings demonstrated that vitamin D supplementation modulates gut microbiota composition, with significant increases observed in bacterial taxa associated with anti-inflammatory and gut health-promoting properties, such as Bifidobacterium and Lactobacillus, as well as an increase in the Bacteroidetes to Firmicutes ratio. Some trials reported enhanced microbial diversity (α and β diversity), and others highlighted variability based on dosage, duration, and baseline vitamin D status. Additionally, specific alterations in microbial biomarkers such as calprotectin and trimethylamine N-oxide, which is linked to vitamin D metabolism, were noted.

Conclusions: Although promising, the findings underscore the heterogeneity in study designs and methodologies, emphasizing the need for standardized approaches to assess causality and clinical relevance. This review provides valuable insights into the interplay between vitamin D and gut microbiota, offering a foundation for personalized nutritional strategies targeting microbiome modulation. Future research should explore the long-term effects of vitamin D supplementation on gut microbiota and its implications for health outcomes in diverse populations.

Systematic review registration: PROSPERO registration no. CRD42024628080.

Keywords: human gut microbiota; immune regulation; microbial diversity; randomized controlled trials; systematic review; vitamin D supplementation.