Immunological Mechanisms of the Gut–brain–cardiovascular Axis in Coronary Heart Disease with Comorbid Anxiety and Depression

Abstract

Coronary heart disease (CHD) is frequently accompanied by anxiety and depression, conditions that markedly worsen cardiovascular outcomes. Increasing evidence indicates that immune dysregulation, driven by gut microbiota alterations, plays a central role in linking psychological disorders with cardiovascular pathology through the gut–brain–cardiovascular axis. This narrative review systematically summarizes recent advances in the immunological mechanisms underlying CHD complicated by anxiety and depression. We focus on gut microbiota–immune interactions, inflammatory signaling pathways, immune-related microbial metabolites, and neuroimmune communication that collectively shape cardiovascular and mental health. Relevant studies addressing immune biomarkers, cytokine profiles, intestinal barrier dysfunction, and immune-modulating therapeutic strategies were critically analyzed. Gut microbiota dysbiosis contributes to intestinal barrier impairment and translocation of microbial products, leading to activation of innate and adaptive immune responses. Elevated pro-inflammatory cytokines, including interleukin 6 and tumor necrosis factor α, serve as key mediators linking systemic inflammation with atherosclerosis and neuropsychiatric symptoms. Microbial metabolites, such as trimethylamine N-oxide, exacerbate immune-driven vascular inflammation, whereas short-chain fatty acids exert immunoregulatory and anti-inflammatory effects. Neuroimmune mechanisms, including hypothalamic–pituitary–adrenal (HPA) axis activation and immune modulation of autonomic function, further integrate psychological stress with cardiovascular immune injury. Immune dysregulation represents a unifying mechanism connecting gut microbiota imbalance, neuropsychiatric disorders, and coronary heart disease. Targeting immune–microbiota interactions within the gut–brain–cardiovascular axis may offer novel diagnostic biomarkers and immunomodulatory therapeutic strategies for CHD patients with comorbid anxiety and depression. This immunological perspective provides a translational framework for future research and integrated clinical management.