A Gut‐Protective <scp>TRPV1</scp> ‐Neuroepithelial Axis: Electroacupuncture Reverses Intestinal Damage in Diet‐Induced Obesity

AIM: Obesity impairs the colonic mucus layer and disrupts intestinal barrier function, leading to chronic inflammation. This study explores whether electroacupuncture can restore intestinal barrier integrity and alleviate chronic intestinal inflammation by promoting goblet cell mucus secretion via the TRPV1-CGRP-RAMP1 axis. It also examines the underlying mechanisms of sensory neuron. Epithelial cell crosstalk in this process, with the goal of providing a new interventional strategy for treating obesity-related intestinal barrier damage and metabolic inflammation. MATERIALS AND METHODS: In a high-fat diet (HFD)-induced obesity model using C57BL/6J mice, we employed tissue-clearing techniques to examine the expression of TRPV1 and CGRP in intact colon tissue. The expression of RAMP1 in goblet cells was assessed by immunohistochemistry. Colon pathology was evaluated using immunofluorescence, haematoxylin and eosin (H&E) staining, and Alcian blue-periodic acid-Schiff (AB-PAS) staining. Furthermore, western blot analysis was performed to measure the expression levels of tight junction proteins and proinflammatory cytokines in the colon tissue. RESULTS: HFD feeding resulted in increased intestinal permeability and aggravation of intestinal inflammation. Notably, electroacupuncture intervention reversed HFD-induced intestinal pathologies. Through targeted ablation of TRPV1 and administration of the RAMP1 antagonist BIBN4096, we further established the essential roles of TRPV1 signalling and the CGRP receptor RAMP1 in maintaining mucus layer thickness and intestinal homeostasis. Under these conditions, the therapeutic efficacy of electroacupuncture was abolished. CONCLUSIONS: We demonstrated that electroacupuncture may promote mucus secretion from goblet cells via the TRPV1-CGRP-RAMP1 axis, thereby suppressing intestinal inflammation. This provides a feasible interventional strategy for treating obesity-related intestinal barrier damage.