Summary:
Vitamin D is best known for its role in bone health, but growing evidence suggests that it may also affect the immune system, gut function, and the body’s response to infection. Researchers are increasingly interested in these broader effects because low vitamin D levels are common and have been linked to a wide range of health problems. The active form of vitamin D works through receptors found throughout the body and helps regulate processes such as immune balance, barrier protection, and inflammatory control. This study is a review based on expert evaluation of research on vitamin D beyond the skeleton, with a focus on gut health, infection, and immune-related disease. This study reviewed findings from observational studies, mechanistic research, and clinical trials to assess where the evidence is strong and where it remains uncertain. This study found that low vitamin D status is consistently associated with disrupted gut barrier function, changes in the microbiome, greater infection risk, and altered immune regulation, including in autoimmune conditions. However, intervention studies showed more mixed results, with outcomes depending on factors such as baseline vitamin D level, dose, formulation, timing, and disease context. Overall, this study suggests that checking for and correcting vitamin D deficiency may be a practical and low-risk strategy for people at higher skeletal or immune risk, although more large, well-designed trials are still needed to define the best treatment approach and the most appropriate target levels.
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Abstract:
Vitamin D, classically linked to calcium-phosphate metabolism and skeletal health, is increasingly recognized as a pleiotropic hormone with effects on gastrointestinal and systemic immune functions. This International Consensus aims to critically evaluate the role of vitamin D in gastrointestinal homeostasis, infection prevention, and immune regulation. A multidisciplinary panel of experts conducted a comprehensive review of the literature, distinguishing between associative evidence from observational studies and causal inferences derived from interventional trials addressing gut barrier integrity, dysbiosis, intestinal cancer prevention, respiratory infections, and autoimmune diseases. While vitamin D deficiency has been consistently associated with alterations in gut microbiota composition, increased intestinal permeability, impaired immune tolerance, and increased susceptibility to infections and autoimmune conditions, evidence from interventional studies remains more variable. Clinical outcomes are influenced by baseline 25(OH)D status, supplementation dose and formulation, timing of intervention, and disease context. Vitamin D supplementation has shown potential benefits in selected settings (i.e., autoimmune diseases and acute respiratory infections), and particularly in cases of documented deficiency. Given its pleiotropic role and favourable safety profile, appropriate screening and optimization of vitamin D represent a low-cost and potentially impactful strategy to support gut barrier function and immune competence. While further research is needed to define these therapeutic applications, maintaining vitamin D concentrations above 20 or 30 ng/mL in individuals at skeletal or immunological risk emerges as a reasonable clinical target. This Consensus Panel supports the integration of vitamin D assessment and correction into routine care for at-risk populations and calls for greater awareness of its extra-skeletal relevance.
Article Publication Date: 26/03/2026
DOI: 10.1007/s11154-026-10026-9
