Vitamin D₃ as an antimicrobial and antiviral immunonutrient in aquaculture

Bacterial and viral diseases continue to remain major problem in aquaculture, and the growing limitations on the use of antibiotics have intensified a growing focus on host-directed nutrition-based disease management strategies. While vitamin D₃ (VD₃) has been recognized for its role in calcium-phosphorus metabolism, it is now increasingly recognized to exert an immunonutrient role in fish, which includes modulation of antimicrobial peptide production, inflammatory regulation, epithelial barrier integrity, oxidative homeostasis, microbiota-associated immune interactions, and antiviral signaling. This review critically synthesizes current knowledge on VD₃ metabolism and vitamin D receptor (VDR)-mediated signaling in relation to disease resilience in cultured aquatic species, with particular emphasis on antibacterial, antiviral, and functional-feed applications. Across experimental studies, VD₃ supplementation has frequently been associated with enhanced phagocytic activity, lysozyme and complement function, antimicrobial peptide induction, cytokine modulation, and improved mucosal stability. Emerging evidence further implicates VD₃ in type I interferon and JAK-STAT-associated antiviral pathways. However, these responses remain highly variable across species, supplementation doses, developmental stages, and environmental conditions, reflecting substantial biological and methodological heterogeneity. Importantly, the current evidence base is still frequently composed of transcriptomic and short-term laboratory studies with comparatively few studies demonstrating functional validity in form of pathogen-load reduction, histopathological protection, improvement of survival, or production level. The translation value for VD₃ is still not fully understood, although it holds promise for use in integrated functional feed systems. Overall, effective application will depend on species-specific dose optimization, long-term safety assessment, and stronger field-scale validation across diverse aquaculture systems. KEY POINTS: • Vitamin D₃ modulate antimicrobial peptides and innate and antibacterial immunity in fish. • VD₃ activates interferon pathways and strengthens antiviral defenses. • Optimal VD₃ dosing improves resilience; field validation is needed in aquaculture.