Gut–brain axis in neurological disorders: mechanistic links and regulatory role of Chinese herbal medicines

The gut–brain axis (GBA) is a bidirectional communication network integrating neural, immune, endocrine, and metabolic pathways that link the gastrointestinal tract and the central nervous system. Increasing evidence implicates gut microbiota dysbiosis in the pathogenesis of neurological disorders, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, autism spectrum disorders, depression, and schizophrenia. This review synthesizes preclinical and clinical evidence to elucidate GBA-mediated mechanisms of neurological dysfunction and critically evaluates the therapeutic potential of Traditional Chinese herbal medicines (TCHMs). We highlight how dysbiosis disrupts immune signaling, microbial metabolite production, intestinal and blood–brain barrier integrity, and neurotransmitter pathways involving serotonin, dopamine, γ-aminobutyric acid, and glutamate, thereby driving neuroinflammation, oxidative stress, and neuronal injury. Particular emphasis is placed on the ability of TCHMs to restore microbial homeostasis, enhance short-chain fatty acid production, strengthen gut barrier function, and regulate neuroendocrine pathways, notably the hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes. These multi-target actions are consistently associated with improved cognitive, behavioral, and neuroinflammatory outcomes across experimental models. The review further identifies emerging synergistic strategies combining TCHMs with microbiota-targeted interventions, such as probiotics and dietary modulation, which enhance correction of dysbiosis and attenuation of neuroinflammatory cascades. Nonetheless, heterogeneity in study design, herbal formulations, and microbiome profiling limits clinical translation. Future progress will require standardized methodologies, multi-omics integration, and precision-based approaches. Overall, this review positions Chinese herbal medicines as promising systems-level modulators of the gut–brain axis for neurological disease management. This graphical abstract illustrates the bidirectional communication between the gut and brain—known as the gut–brain axis and highlights how Chinese herbal medicines modulate this system to counteract neurological disorders. The central section depicts the gut microbiota, emphasizing beneficial bacterial genera such as Bifidobacterium , Lactobacillus , Akkermansia muciniphila , Faecalibacterium prausnitzii , Roseburia , and Prevotella , which play crucial roles in maintaining intestinal and neural homeostasis. Chinese herbal medicines act on the gut ecosystem by enhancing microbial diversity, promoting beneficial bacterial growth, and restoring metabolic balance. Under healthy conditions, these gut microbes contribute to gut barrier integrity, produce short-chain fatty acids (SCFAs), exert anti-inflammatory effects, and modulate neurotransmitter production and immune responses, all of which are essential for proper brain function. However, dysbiosis characterized by overgrowth of pathogenic bacteria such as Escherichia , Shigella , Helicobacter pylori , Akkermansia , and Clostridium leads to increased intestinal permeability (leaky gut), allowing bacterial endotoxins like lipopolysaccharides (LPS) to enter the bloodstream. This triggers neuroinflammation, altered microbial metabolite profiles, immune dysregulation, and neurotransmitter imbalance, contributing to the pathogenesis of neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's diseases.