Psychological stress and immune dysregulation: Insights from neuroimmunology and the gut-brain-immune axis

The interplay between mental health, immune function, and gut microbiota has garnered increasing attention in recent years, with mounting evidence indicating that psychological stress and depression are increasingly associated with alterations in immune responses and systemic health. Chronic stress and depression are closely associated with immune dysregulation and have been implicated in the onset and progression of autoimmune diseases, cardiovascular disorders, cancer, and other inflammation-related conditions，although these relationships are complex and not strictly causal. Emerging research highlights the gut-brain-immune axis as a critical mediator of these effects, where alterations in gut microbiota composition, microbial metabolites, and intestinal barrier integrity modulate systemic inflammation, immune cell function, and neural activity. This review examines the intricate relationship between depression, stress, immune dysregulation, and gut microbiota, focusing on how psychological states are associated with changes in immune markers, inflammatory pathways, and cellular immunity. We discuss the roles of key neural systems, including prefrontal-limbic circuits and brainstem-autonomic pathways, in shaping immune-related processes, the influence of neurotransmitters including serotonin and norepinephrine, and the impact of autonomic nervous system activity on immune modulation. Furthermore, we explore how gut microbial dysbiosis and microbial metabolites contribute to neuroimmune interactions, providing novel insights into the mechanisms linking psychological and immune health. By synthesizing current evidence, this review underscores the potential for integrated therapeutic strategies that simultaneously target mental health, immune function, and gut microbiota, and highlights avenues for future research in psychoneuroimmunology and clinical translation.