The regulation of neurogenesis, the complex process of producing and differentiating new brain tissue cells, is influenced by a complex interaction of internal and external factors. Over the past decade, extensive research has been conducted on neurotrophins and their key role in adult neurogenesis, as well as their impact on diseases such as depression. Among neurotrophins, the brain-derived neurotrophic factor (BDNF) has been the subject of comprehensive studies on adult neurogenesis, and scientific evidence supports its necessity for neurogenesis in the subventricular zone of the hippocampus. A novel area of research is the emerging role of gut microbiota as a significant contributor to neurogenesis and neurotrophin production. Studies have shown that reduced BDNF levels can lead to mood disorders, which are observed in intestinal dysbiosis, characterized by an imbalance in the composition and quantity of the intestinal microbiota. There is evidence in the literature that there is a link between brain function and gut microbiota. Physical activity, and especially the regularity and intensity of exercise, is important in relation to the level of BDNF and the intestinal microbiota. Probiotics, prebiotics and physical activity may have a positive effect on the intestinal microbiota, and therefore also on the level of the brain-derived neurotrophic factor.

Background/Objectives: Vitamin D deficiency is prevalent in higher-latitude regions and among older adults, and has been linked to depressive symptoms and cognitive decline, although the neurobiological link remains unclear. Brain-derived neurotrophic factor (BDNF) may be a key modulator and mediator of vitamin D-related neuroprotection. Methods: Selected databases (2009–2025) were searched for specific studies reporting vitamin D exposure, BDNF, and mood or cognitive outcomes. Risk of bias was appraised with RoB 2, Newcastle–Ottawa Scale or SYRCLE. Results: Thirteen studies were included. High-dose vitamin D improves mood primarily when levels are low. Supplementation of at least 2000 IU/day for 12 weeks reduced BDI scores by 1.7–7.6 points and increased BDNF levels by ~7%. Each 1 ng/mL increase in 25(OH)D levels decreased the likelihood of depressive symptoms, especially when BDNF levels were high. In animal studies vitamin D increases hippocampal BDNF and reverses stress-induced depressive behavioral deficits. Adequate vitamin D intake is associated with improved cognitive performance and a dose-dependent increase in BDNF. Each 10 ng/mL increase in 25(OH)D was associated with a 0.6-point increase in MMSE scores and a 15% increase in serum BDNF. Low vitamin D status in children may predict cognitive decline. Animal studies have shown that supplementation with 500–10,000 IU/kg for at least 3 weeks increased hippocampal BDNF and improved biochemical markers of aging. Conclusions: Vitamin D supplementation may support mood and cognition via BDNF modulation, especially in people with insufficient vitamin D levels (<30 ng/mL), but long-term, adequately powered studies with objective tools are required.