Naomaitong ameliorates cerebral and intestinal injury in ischemia stroke via modulation of gut-brain axis interactions: Akkermansia muciniphila-mediated regulation of tryptophan-serotonin metabolic pathways.

Ischemic stroke (IS) is a major cause of disability and mortality, yet therapies targeting the gut-brain axis remain underdeveloped. Naomaitong (NMT), a traditional Chinese medicine, shows promise for IS treatment, but its mechanisms involving gut microbiota and metabolic pathways are unclear. This study investigates whether NMT enhances post-stroke recovery by modulating Akkermansia muciniphila (AKK) and the tryptophan-serotonin pathway. Using a middle cerebral artery occlusion/reperfusion (MCAO/R) rat model, we evaluated NMT's effects via TTC staining, neurological scoring, histopathology, and LC-MS metabolomics of cerebrospinal fluid (CSF), plasma, and colon. AKK abundance was quantified by qPCR, while ELISA and immunohistochemistry assessed 5-HT metabolites and enzymes. NMT significantly reduced cerebral infarct size ( p < 0.05), improved neurological function ( p < 0.01), and restored intestinal barrier integrity. Metabolomics revealed NMT's modulation of the tryptophan pathway: colonic 5-HT decreased (p < 0.01), while plasma and CSF 5-HT increased (p < 0.05). NMT enriched AKK abundance ( p < 0.05) and regulated 5-HT-related enzymes (MAO-A, SERT, TPH1). AKK supplementation replicated NMT's benefits, confirming its role in metabolic and functional recovery. NMT promotes post-stroke recovery by enriching AKK and optimizing tryptophan-serotonin metabolism, demonstrating dual protection against cerebral and intestinal injuries. This study is the first to link NMT's therapeutic effects to gut-brain axis modulation via microbiota-metabolite crosstalk.