Acupuncture modulates the gut–brain axis in ischemic stroke: A narrative review of mechanisms and therapeutic potential

Ischemic stroke is one of the leading causes of mortality and disability worldwide, with limited therapeutic options due to the narrow therapeutic window and the risk of reperfusion injury. This narrative review presents a new perspective on how acupuncture, a core modality of traditional Chinese medicine, may facilitate stroke recovery by modulating the gut-brain axis (GBA). The GBA is emerging as a critical determinant of stroke pathogenesis, in which cerebral ischemia not only causes local injury but also triggers systemic disturbances, particularly in the gastrointestinal tract. Stroke rapidly induces intestinal dysbiosis, which in turn amplifies cerebral infarction and neuroinflammation through bidirectional gut-brain communication mechanisms.

The review proposes that acupuncture acts through four interconnected mechanistic pathways. First, it restores intestinal barrier integrity through targeted microbial reprogramming, enriching commensal bacteria such as Akkermansia and increasing the production of short-chain fatty acids (SCFAs), particularly butyrate, which serves as an energy substrate for enterocytes and as an epigenetic regulator. This modulation leads to increased tight junction proteins (ZO-1, occludin), strengthening the intestinal barrier and reducing bacterial translocation. Second, acupuncture rebalances neuroendocrine activity through activation of the anti-inflammatory vagal-adrenal reflex.

Stimulation at points such as ST-36 activates specific sensory neurons that express PROKR2-Cre, initiating a neural pathway that propagates through the nucleus of the solitary tract to the dorsal motor nucleus of the vagus, suppressing the release of systemic cytokines. Simultaneously, stimulation at cephalic points such as GV-20 modulates hyperactivity of the hypothalamic-pituitary-adrenal axis, reducing corticosteroid levels and restoring sympathetic-vagal balance. Third, acupuncture reprograms the gut-derived metabolic profile, increasing neuroprotective metabolites such as SCFAs and indole-3-propionic acid (IPA), while reducing neurotoxic compounds such as trimethylamine N-oxide (TMAO). IPA binds to melatonin receptors (MT1/MT2), activating mitochondrial protection pathways that attenuate oxidative stress and neuronal apoptosis.

Fourth, acupuncture restores immune homeostasis through modulation of peripheral-central immune crosstalk. Evidence shows that electroacupuncture suppresses the migration of gut-derived γδ T cells to meningeal compartments, while increasing the accumulation of regulatory T cells (Tregs) in both the brain parenchyma and the intestinal lamina propria, alleviating IL-17A-mediated disruption of the blood-brain barrier. The review highlights that these mechanisms operate not as sequential pathways but as components of a dynamic and adaptive network. Acupuncture acts as a systemic initiator, engaging these pathways in parallel or in rapid iterative cycles.

For example, vagal activation rapidly alters intestinal motility and secretion, shaping the microbial niche, while simultaneously, changes in microbial metabolites can directly modulate epithelial integrity, local immune cells, and even signal back to central circuits. From a clinical perspective, emerging evidence from stroke patients is encouraging. Studies in patients with post-stroke depression have shown that manual acupuncture modulates the intestinal microbiota and improves depression scores, potentially through regulation of the NLRP3 inflammasome. In addition, high-quality clinical evidence from other inflammatory conditions, such as Crohn's disease, strongly supports the capacity of acupuncture to restore intestinal homeostasis.

Despite the promising advances, significant limitations persist. Most of the current evidence is correlational and limited to preclinical models, with insufficient causal validation. Future studies should prioritize causal dissection through multimodal integration, combining optogenetic or chemogenetic manipulation of vagal and hypothalamic circuits with humanized microbiota models. Individual heterogeneity in microbiota composition, lesion topology, and pharmacological context represents a formidable obstacle to reproducibility in heterogeneous human populations.

Standardization of acupuncture parameters is emerging as a critical need, given that wide variation in stimulation frequency, intensity, waveform, duration, and combinations of acupoints makes it difficult to compare studies and translate findings clinically. This review establishes acupuncture as a systemic regulator capable of restoring GBA homeostasis after stroke, providing a mechanistic framework for precision and translational interventions. The knowledge synthesized not only elucidates the systemic mechanisms of acupuncture but also highlights its potential as a precision neuromodulatory therapy, guiding future translational research in integrative stroke care.