Electroacupuncture suppresses motor impairments via microbiota-metabolized LPS/NLRP3 signaling in 6-OHDA induced Parkinson's disease rats

Emerging evidence indicates that electroacupuncture (EA) exerts significant therapeutic effects on Parkinson's disease (PD)-related symptoms, with the immune mechanisms of the gut-brain axis playing a pivotal role in PD pathophysiology. This study aimed to explore whether EA mitigated PD-related symptoms and conferred neuroprotection to dopaminergic neurons in a 6-hydroxydopamine (6-OHDA) rat model by modulating the microbiota-metabolized lipopolysaccharide (LPS)/NLRP3 pathway. EA treatment ameliorated motor and anxiety symptoms in 6-OHDA rats and elevated the levels of TH. Metabolomic analysis indicated that the therapeutic effects of EA are associated with the gut microbiota and the NOD-like receptor signaling pathway. 16S rRNA sequencing demonstrated that EA significantly modified the composition of the gut microbiota, evidenced by alterations in the relative abundance of 16 genera, and led to the downregulation of the LPS and NOD-like receptor signaling pathways. Additionally, EA was found to attenuate intestinal inflammation, decrease serum inflammatory markers, reduce neuroinflammation, and suppress the overexpression of microglia and astrocytes, while concurrently preserving the integrity of the intestinal and blood-brain barriers. Fecal microbiota transplantation experiments further substantiated the pivotal role of gut microbiota in mediating the anti-PD effects of EA. In summary, EA has the potential to alleviate PD-related symptoms and safeguard dopaminergic neurons by rectifying gut microbiota dysbiosis and downregulating the LPS/NLRP3 immune pathway along the gut-brain axis in PD rat models.