Colitis-associated gut–vagus–brain signaling integrates tumorigenesis and neuroinflammation: comparative regulation by vagotomy and atropine

作者：Duo Yun, Cong Yang, Xue Wang, Le Zhou, Mengzhen Jia, Jiarui Liang, Xinyu Hu, Liyuan Niu, Fengfeng Mo, Jiafeng Wang, Zheng Liu · 发表于：Journal of Neuroinflammation · 年份：2026 · DOI：10.1186/s12974-026-03752-z · 被引用次数：1 · 研究领域：Vagus Nerve Stimulation Research、Gut microbiota and health、Tryptophan and brain disorders

BACKGROUND: Colitis-associated cancer (CAC) is frequently accompanied by neuropsychiatric comorbidities, yet the underlying gut-brain signaling pathways remain elusive. Emerging evidence highlights the gut-brain axis, particularly the vagus nerve, as a pivotal mediator linking gastrointestinal pathology with neuropsychiatric dysfunction. This study aimed to dissect the dual roles of vagal signaling in a murine CAC model and to evaluate the therapeutic potential of the muscarinic antagonist atropine on CAC. METHODS: The azoxymethane/dextran sulfate sodium (AOM/DSS) was adopted to induce CAC mice model. We employed unilateral vagotomy and pharmacological intervention with atropine, a muscarinic antagonist, in CAC mice. We assessed colon tumorigenesis, intestinal inflammation, anxiety/depression-like behaviors, and neuroinflammation of CAC mice under vagotomy and atropine treatment. Vagotomy and retrograde viral tracing were used to verify the essential role of vagus nerve signaling in activating neurons in brain regions linked to inflammation-induced depression and anxiety, thereby clarifying the gut-neuro-brain circuit mechanism. RESULTS: The findings revealed that CAC progression was associated with depression- and anxiety-like behaviors. Vagotomy significantly alleviated these behaviors, reduced c-fos expression in the NTS and lateral habenula/ midbrain-hindbrain boundary (LHb/MHb), and retrograde tracing confirmed a functional gut–NTS–LHb/MHb circuit activated by intestinal...