Electroacupuncture Alleviates Brain Injury Through Vagus Nerve Activation and Gut Microbiota in a Rat Model of Ischemic Stroke

Nov 10, 2025Journal of the American Heart Association

Electroacupuncture may reduce brain damage after stroke by activating the vagus nerve and changing gut bacteria in rats

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Abstract

Electroacupuncture significantly reduced infarct volumes by 33% and improved survival rates by 30% in a rat stroke model.

Electroacupuncture improved neurological outcomes and reduced infarct volumes at 3 to 7 days post-stroke compared to controls.
The neuroprotective effects of electroacupuncture were abolished by vagotomy, indicating a vagus nerve-dependent mechanism.
Electroacupuncture restored gut barrier integrity through increased production of a specific sugar molecule (fucosylation).
Shifts in gut microbiota included an increase in beneficial bacteria and a decrease in harmful bacteria, which were reversed by vagotomy.
Fecal microbiota transplant from electroacupuncture-treated rats replicated neuroprotective effects in germ-free rats, while transplant from vagotomized rats showed no benefits.

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BACKGROUND: Emerging evidence implicates gut microbiota dysbiosis in exacerbating stroke pathogenesis via the gut-brain axis, suggesting novel therapeutic targets. While electroacupuncture (EA) demonstrates anti-inflammatory effects through vagus nerve activation, its neuroprotective mechanisms via vagus nerve-microbiota crosstalk remain unexplored.

METHODS: Rats with middle cerebral artery occlusion received daily ST36 (Acupoint Zusanli) EA for 1 to 7 days postischemia. Subdiaphragmatic vagotomy and fecal microbiota transplant were implemented to validate pathway specificity. Multimodal assessments included longitudinal neurological scoring, infarct volume, systemic/neuroinflammatory profiling (enzyme-linked immunosorbent assay, immunohistochemistry), intestinal fucosylation dynamics (quantitative polymerase chain reaction, lectin staining), and 16S ribosomal RNA sequencing of gut microbiota.

RESULTS: EA significantly improved neurological outcomes and reduced infarct volumes at 3 to 7 days after middle cerebral artery occlusion (versus controls), which was abolished by vagotomy. Mechanistically, EA restored gut barrier integrity through vagus-dependent upregulation of fucosyltransferase 2 (Fut2)-driven epithelial α1,2-fucosylation, enhancing mucin 2+ goblet cell density and tight junction protein expression (ZO-1/occludin/claudin-1). Concurrent microbiota shifts included Lactobacillales/Bacteroidales enrichment (linear discriminant analysis >4.0) and pathobiont suppression, which was reversed by vagotomy. Crucially, fecal microbiota transplant from EA-treated donors replicated neuroprotection in germ-free recipients, achieving 33% infarct reduction and 30% survival improvement (=0.012), whereas fecal microbiota transplant from vagotomized donors showed no therapeutic benefits. P

CONCLUSIONS: EA at ST36 produced neuroprotection through activating vagal efferent pathways to orchestrate intestinal mucosal repair via Fut2-mediated fucosylation, which reshape microbial ecosystems and attenuate neuroinflammation. These findings establish a previously unrecognized vagus nerve-gut-brain axis mechanism for stroke recovery, positioning microbiota-directed neuromodulation by EA as a translatable therapeutic strategy.

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Electroacupuncture Alleviates Brain Injury Through Vagus Nerve Activation and Gut Microbiota in a Rat Model of Ischemic Stroke

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