Modulation of the Brain–Gut–Microbiota Axis by Traditional Chinese Heat-Clearing and Bowel-Unblocking Therapy in Stroke-Associated Pneumonia: Pharmacological Mechanisms and Clinical Implications

Abstract

Stroke-associated pneumonia (SAP) is a common and potentially fatal complication of acute stroke that substantially increases morbidity, mortality, and healthcare burden. Traditionally attributed to aspiration and dysphagia, SAP is increasingly recognized as a systemic consequence of stroke-induced neuroimmune dysfunction involving the brain–gut–microbiota axis. Acute cerebral ischemia disrupts autonomic and neuroendocrine homeostasis, leading to intestinal dysmotility, impaired epithelial barrier integrity, and gut microbiota dysbiosis. Acute stroke induces neuroendocrine stress, intestinal dysbiosis, and immune suppression. These changes disrupt gut-derived immune cell trafficking, including Th17 cells, regulatory T cells, and innate lymphoid cells (ILC2s), leading to impaired pulmonary immune defense. Heat-clearing therapy attenuates systemic inflammation, restores intestinal homeostasis, and rebalances gut–lung immune communication, thereby lowering susceptibility to SAP. Traditional Chinese medicine (TCM), particularly heat-clearing and bowel-unblocking therapy, has long been applied in the treatment of acute stroke and severe pulmonary disorders based on the lung–large intestine interior–exterior relationship. Emerging experimental and clinical evidence suggests that this approach exerts multi-target regulatory effects on the brain–gut–lung axis. Pharmacological studies indicate that representative herbs, including Rheum palmatum, Scutellaria baicalensis, and Coptis chinensis, suppress excessive inflammatory signaling, restore intestinal barrier function, and promote microbiota modulation by restoring microbial composition and function. Multi-omics analyses further demonstrate enhanced short-chain fatty acid production, microbial metabolic rebalancing, and restoration of systemic immunity. Although high-quality randomized evidence remains limited, converging data from cohort studies and mechanistic research support the biological plausibility of gut-targeted TCM interventions for SAP prevention and treatment.