Research Advances in Multimodal Framework-Based Identification and Therapeutic Management of Post-Stroke Depression via the Microbiota-Gut-Brain Axis

Patients with post-stroke depression typically present with psychosocial impairments, including depressed mood and pessimism, accompanied by behavioral manifestations such as social withdrawal. These symptoms significantly impede rehabilitation compliance while elevating risks of self-harm and suicidal ideation. Recent advances in microbiota-gut-brain axis research have elucidated bidirectional communication pathways between the gut microbiota-mediated neuroendocrine-immune network and the central nervous system. Dysregulation of microbiota-gut-brain axis homeostasis may precipitate neuroinflammatory cascades and NE metabolic disturbances, potentially driving post-stroke depression pathogenesis. This paper attempts to propose a multimodal precision diagnosis and treatment framework for post-stroke depression based on the microbiota-gut-brain axis mechanism, representing the first effort to integrate perspectives from neurobiology, gut microbiota, and Traditional Chinese Medicine with modern scientific interpretation to construct such a framework. The paper encompasses four levels: mechanism, integration, evidence, and application. At the mechanism level, it explores the bidirectional regulatory mechanisms of the microbiota-gut-brain axis in post-stroke depression to identify potential therapeutic targets. At the integration level, it refines core principles for constructing a multimodal system applicable to post-stroke depression and builds an microbiota-gut-brain axis based multimodal research framework for post-stroke depression. At the evidence level, by integrating neuroimaging, metabolomics, and microbiomics technologies, it discusses the potential of a multimodal identification system, which is expected to aid in identifying molecular-cellular-circuit mechanisms associated with post-stroke depression. At the application level, it reviews research progress in treating post-stroke depression using the central nervous system interventions, gut microbiota modulation, pharmaceuticals, complementary medicine, and lifestyle interventions, summarizing them into multimodal interventional strategies to inform clinical practice for comprehensive treatment. By incorporating the roles of gut microbiota and oxidative stress in stroke-related complications and neuroimmune pathologies, this review offers a more comprehensive theoretical basis for the precise treatment of post-stroke depression. Future research should rely on large-scale cohorts and artificial intelligence to clarify the dynamic interactive networks of multiple biomarkers within critical time windows, ultimately facilitating the translation of this multimodal framework from theory to clinical practice.