Electroacupuncture ameliorates Autism Spectrum Disorder via modulating the gut-brain axis depending on the integrity of vagus nerve

Autism spectrum disorder (ASD) is a neurodevelopmental disease characterized by behavioral and neurological abnormalities. Numerous pieces of evidence indicate a strong association between ASD and neuroinflammation mediated by gut microbiota and microglial activation. Previous studies have shown that the therapeutic effects of an acupuncture protocol targeting the bacteria-gut-brain axis in a well-established ASD mouse model induced by prenatal exposure to valproic acid (VPA). We demonstrated that electroacupuncture significantly alleviates behavioral symptoms in VPA model. However, the precise mechanisms remain insufficiently elucidated. In this study, we confirmed that electroacupuncture markedly improved behavioral symptoms in ASD mice. We conducted gut microbiota transplantation from electroacupuncture-treated mice to untreated ASD mice, improving behavioral outcomes in untreated ASD mice. Conversely, by transplanting gut microbiota from ASD mice into electroacupuncture-treated mice, we successfully mitigated the beneficial behavioral effects of acupuncture. We analyzed inflammatory markers in the microglial activation from cerebral cortex and hippocampus tissues, revealing that acupuncture exerts robust anti-neuroinflammatory effects in ASD mice. To further validate the mechanism, we performed vagotomy in ASD mice, which abolished the therapeutic benefits of acupuncture. Our findings establish that the behavioral improvements observed in ASD mice are intricately linked to the diversity and abundance of gut microbiota. Furthermore, regulatory effects of electroacupuncture on ASD behaviors are mediated via bacteria-gut-brain axis, dependent on intact vagus nerve signaling. This study provides compelling evidence for the potential of acupuncture to modulate central neuroinflammation through vagus nerve-mediated gut microbiota regulation, offering novel avenue into its therapeutic application for neurodevelopmental disorders such as ASD.