Nodose ganglion vagal afferents promote electroacupuncture efficacy in the gut-brain axis via proteasome restoration and CXCL10 suppression.

Abstract

Abstract: Electroacupuncture is a potent neuromodulatory strategy for mitigating intestinal pathologies. Nevertheless, the role of primary visceral sensory apparatuses in transducing somatosensory acupuncture signals remains unclear. Here, we sought to delineate the neuroanatomical necessity and cell type-specific molecular reprogramming within the nodose ganglion, the primary sensory relay of vagal afferents, underlying electroacupuncture-mediated intestinal homeostasis. Retrograde tracing confirmed a direct neuroanatomical conduit between the distal colon and nodose ganglion sensory neurons. Under pathological conditions, the nodose ganglion dynamically sensed colonic inflammation, manifesting as profound transcriptomic shifts. Electroacupuncture at Zusanli (ST36) significantly attenuated UC severity, suppressed systemic inflammation, and restored both physical (zonula occludens-1 and claudin-1) and chemical (Muc2 and Tff3) mucosal barriers. Crucially, targeted ablation of nodose ganglion vagal afferents completely abolished these macroscopic and molecular protective effects, along with the blockade of electroacupuncture-evoked cervical vagal discharge and colonic motility reflexes. Multomic deconvolution revealed that colitis triggered severe proteasome dysregulation and aberrant Cxcl10-mediated satellite glia/macrophage-to-neuron crosstalk within the nodose ganglion. Remarkably, electroacupuncture precisely reversed this pathological reprogramming by upregulating the expression of core proteasome-associated hub genes (Psma2, Psmd14, and Eif2s1) and potently quenching Cxcl10-induced neuroimmune hypersensitivity. These findings suggest that vagal sensory afferents within the nodose ganglion function as indispensable anatomical bottlenecks and functional responders for electroacupuncture-mediated colitis remission. By expanding the classic "acupoint-organ-center" paradigm, these findings demonstrate that disease-state sensory ganglia actively gate neuromodulatory therapy, providing a high-resolution molecular foundation for the clinical translation of electroacupuncture in treating intestinal disease.