Vitamin D in Gut and Systemic Immune Tolerance and in Infections’ Risk: An International Evidence-Based Consensus Statement

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.