Vitamin D improves the Gut Microbiota - review July 2025

Effect of Vitamin D Supplementation on Human Gut Microbiota - July 2025

Effect of Vitamin D Supplementation on Human Gut Microbiota: A Systematic Review of Randomized Controlled Trials
Nutr Rev. 2025 Jul 17:nuaf120. doi: 10.1093/nutrit/nuaf120
Falak Zeb 1, Tareq Osaili 1 2 3, Mona Hashim 1 2, Nadia Alkalbani 1 2, Dimitrios Papandreou 1 2, Leila Cheikh Ismail 1 2 4, Farah Naja 1 2 5, Hadia Radwan 1 2, Hayder Hasan 1 2, Reyad Shakir Obaid 1 2, Ioannis Savvaidis 1 6, Sharifa AlBlooshi 7, Iftikhar Alam 8

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.

Perplexity AI review of the study (pdf was not available)

This systematic review, published in July 2025 by Falak Zeb and colleagues, represents a comprehensive analysis of 14 randomized controlled trials (RCTs) examining the effects of vitamin D supplementation on human gut microbiota composition1. The study analyzed data from 1,458 participants across various health conditions and supplementation protocols to provide evidence-based insights into the relationship between vitamin D and gut microbiome health.
The systematic review followed the PRISMA guidelines and included studies published between January 2015 and November 20241. The research team searched multiple databases including MEDLINE, Web of Science, Scopus, and the Cochrane Library to identify relevant RCTs1.
The inclusion criteria required studies to:

Be randomized controlled trials
Investigate vitamin D supplementation effects on gut microbiota
Use high-throughput sequencing techniques for microbiome analysis
Include outcomes related to microbial abundance, composition, and diversity1

The study was registered with PROSPERO (CRD42024628080) and encompassed participants with varying health statuses and different vitamin D supplementation regimens1.

Microbial Composition Changes

The review demonstrated that vitamin D supplementation significantly modulates gut microbiota composition1. The most notable changes observed across the analyzed studies included:
Beneficial Bacteria Enhancement: Vitamin D supplementation led to significant increases in bacterial taxa associated with anti-inflammatory and gut health-promoting properties, particularly Bifidobacterium and Lactobacillus1. These findings are consistent with multiple individual studies showing that vitamin D supplementation enriches members of the Bifidobacteriaceae family 2 3 4.
Phylum-Level Modifications: The supplementation resulted in an increased Bacteroidetes to Firmicutes ratio1, which is considered a marker of improved gut health. This finding aligns with research showing that vitamin D supplementation decreases the relative abundance of Firmicutes while increasing Bacteroidetes 4 5. A high Firmicutes to Bacteroidetes ratio has been associated with obesity and metabolic disorders 4.

Microbial Diversity Enhancement

Several trials within the systematic review reported enhanced microbial diversity, including both alpha and beta diversity measures1. This is particularly significant as increased gut microbial diversity is generally associated with better health outcomes 4 6. Studies have shown that vitamin D supplementation leads to increases in observed operational taxonomic units (OTUs) and Chao1 indices, indicating greater bacterial richness 4.

Dose-Response Relationships

The review identified variability in outcomes based on dosage, duration, and baseline vitamin D status1. Research demonstrates dose-dependent effects, with studies showing that higher doses of vitamin D supplementation (ranging from 4,000 to 10,000 IU daily) produce more pronounced changes in specific bacterial genera like Bacteroides and Parabacteroides 7 8.

Biomarker Alterations

The systematic review noted specific alterations in microbial biomarkers, including changes in calprotectin and trimethylamine N-oxide (TMAO)1. These biomarkers are linked to vitamin D metabolism and gut health. Additionally, studies have shown that vitamin D supplementation can enhance tetracosahexaenoic acid levels1.

Mechanisms of Action

Vitamin D Receptor (VDR) Pathway

The effects of vitamin D on gut microbiota are primarily mediated through the vitamin D receptor (VDR), which regulates intestinal barrier integrity and controls both innate and adaptive immunity in the gut 9 10. The VDR is expressed in intestinal epithelial cells and immune cells, where it influences antimicrobial peptide production and inflammatory responses 10.

Antimicrobial Peptide Regulation

Vitamin D supplementation induces the expression of antimicrobial peptides such as cathelicidin and β-defensins, which help maintain microbial balance and protect against pathogenic bacteria 11 10. This mechanism contributes to the observed reduction in opportunistic pathogens following vitamin D supplementation 11.

Metabolic Interactions

The review highlighted that vitamin D supplementation results in notable metabolic shifts and rewiring of gut microbial-metabolic associations1. Research shows that vitamin D affects amino acid metabolism, particularly pathways involving glycine, serine, and threonine 3 12.

Health Outcomes

The systematic review's findings suggest that vitamin D supplementation may contribute to improved gut health through several mechanisms:

Reduced Inflammation: The increase in anti-inflammatory bacterial species and improved Bacteroidetes to Firmicutes ratio may help reduce systemic inflammation1 4
Enhanced Immune Function: Changes in microbial composition support better immune regulation through VDR-mediated pathways 9 10
Metabolic Health: The observed microbial changes are associated with improved metabolic outcomes and reduced risk of metabolic syndrome 4

Disease Prevention

Research indicates that vitamin D supplementation may have protective effects against various conditions:

Inflammatory Bowel Disease: Studies show that vitamin D can reduce intestinal inflammation and improve symptoms in patients with active ulcerative colitis 13
Colorectal Cancer: The microbial changes induced by vitamin D supplementation may contribute to colorectal cancer prevention through enhanced beneficial bacteria and reduced inflammation 3 12

Study Heterogeneity

The systematic review acknowledges significant heterogeneity in study designs and methodologies across the included trials1. This variability makes it challenging to draw definitive conclusions about optimal dosing, duration, and patient populations.

Mechanistic Understanding

While the review establishes clear associations between vitamin D supplementation and gut microbiota changes, the underlying mechanisms remain incompletely understood1. The indirect effects of vitamin D on bacteria (since bacteria don't express VDR) suggest complex host-mediated pathways that require further investigation 9.

Individual Variation

The review noted substantial individual variation in response to vitamin D supplementation, with some participants showing more pronounced microbiota changes than others1. Research has identified specific bacterial species like Bacteroides acidifaciens that may serve as biomarkers for vitamin D responsiveness 4.

Standardization Needs

The systematic review emphasizes the critical need for standardized approaches to assess causality and clinical relevance in vitamin D-microbiota research1. This includes:

Standardized supplementation protocols
Consistent microbiome analysis methods
Uniform outcome measures
Appropriate control groups

Long-term Studies

Future research should explore the long-term effects of vitamin D supplementation on gut microbiota and subsequent health outcomes in diverse populations1. Most current studies focus on short-term interventions (8-12 weeks), limiting understanding of sustained effects.

Personalized Medicine

The review supports the development of personalized nutritional strategies targeting microbiome modulation based on individual baseline vitamin D status and gut microbiota composition1. This approach could optimize therapeutic outcomes while minimizing potential adverse effects.

Conclusion

This systematic review provides compelling evidence that vitamin D supplementation significantly modulates human gut microbiota composition, promoting beneficial bacterial species while enhancing microbial diversity1. The findings support the role of vitamin D in maintaining gut health through VDR-mediated pathways and suggest potential therapeutic applications for various inflammatory and metabolic conditions.
However, the heterogeneity in study designs and the complexity of vitamin D-microbiota interactions underscore the need for more rigorous, standardized research approaches1. As our understanding of these relationships deepens, vitamin D supplementation may become an increasingly important tool for precision medicine approaches targeting gut microbiome health.
The implications of this research extend beyond gut health, potentially influencing our understanding of vitamin D's role in immune regulation, metabolic health, and disease prevention through microbiome-mediated mechanisms1 9 10.
References

Vitamin D improves the Gut Microbiota - review July 2025

Effect of Vitamin D Supplementation on Human Gut Microbiota - July 2025

Perplexity AI review of the study (pdf was not available)

Microbial Composition Changes

Microbial Diversity Enhancement

Dose-Response Relationships

Biomarker Alterations

Mechanisms of Action

Vitamin D Receptor (VDR) Pathway

Antimicrobial Peptide Regulation

Metabolic Interactions

Health Outcomes

Disease Prevention

Study Heterogeneity

Mechanistic Understanding

Individual Variation

Standardization Needs

Long-term Studies

Personalized Medicine

Conclusion

Related items in Vitamin D Life

Health Problems and D

Vitamin D improves the Gut Microbiota - review July 2025

Effect of Vitamin D Supplementation on Human Gut Microbiota - July 2025

Perplexity AI review of the study (pdf was not available)

Microbial Composition Changes

Microbial Diversity Enhancement

Dose-Response Relationships

Biomarker Alterations

Mechanisms of Action

Vitamin D Receptor (VDR) Pathway

Antimicrobial Peptide Regulation

Metabolic Interactions

Health Outcomes

Disease Prevention

Study Heterogeneity

Mechanistic Understanding

Individual Variation

Standardization Needs

Long-term Studies

Personalized Medicine

Conclusion

Related items in Vitamin D Life

Page actions

Health Problems and D