Zinc and Depression: From Neurobiological Functions to Gut–Brain Interactions

The global prevalence of depression and its profound burden on public health create an urgent need to explore novel interventions beyond conventional therapeutic strategies. Zinc, a key regulator in the central nervous system, exerts multiple biological functions beyond maintaining neurotransmitter homeostasis, including inhibiting neuroinflammation, restoring neuroplasticity, and modulating gut microenvironmental homeostasis. This review summarizes the evidence linking zinc deficiency to the onset and development of depression, with a specific focus on the role of gut microbiota. It also discusses different forms of zinc supplements, highlighting synergistic interventions that combine novel zinc complexes with probiotics. Together, these lines of evidence provide a theoretical basis for innovative adjunctive strategies for depression.