脑-肠轴功能稳态的维持是机体发挥正常生理功能的基础，该轴功能紊乱或失衡将导致多器官和多系统功能障碍，然而有关肠-脑轴的研究报道较少。研究表明不良环境因素刺激将影响脑-肠轴双向调节功能稳态，不但诱发重大脑部疾病，还导致胃肠功能紊乱，为此，明确肠-脑轴稳态维持机制并探讨其失衡分子机制具有重大战略意义。前期我们发现新生期不良刺激导致外周神经敏化、慢性内脏痛和肠道菌群紊乱。本项目拟在此基础上研究肠道菌群紊乱所致肠-脑轴稳态失衡在慢性痛中枢敏化中的作用，验证前扣带皮层-杏仁核神经环路功能增强是慢性痛中枢敏化的重要机制，深入研究DNA甲基化稳态失衡是环境-基因相互作用导致肠-脑轴稳态失衡和慢性痛的表观调控机制。本课题的顺利实施有助于阐明肠-脑轴双向调控稳态与功能性胃肠疾病和中枢敏化之间的关系，明确肠道菌群和相关脑区作为功能性胃肠疾病早期诊断标志物或药物靶标的潜在应用价值，为后续转化医学研究奠定基础。

The maintenance of the Brain-Gut Axis (BGA) homeostasis is the basis of the normal physiological function of the body. The dysfunction or imbalance of the axis will lead to malfunction or diseases of multiple organs and/or multi-systems. However, researches on the Gut-Brain Axis (GBA) are relatively few. A growing body of research evidence shows that the severe external environmental stressors will seriously affect bidirectional regulations of the brain-gut axis homeostasis, which not only causes serious brain diseases, but also leads to gastrointestinal dysfunction. Therefore, to investigate the molecular mechanisms underlying the GBA homeostasis and its imbalance has great strategic significance. We have previously demonstrated that stress or colorectal inflammatory stimulation during neonatal period of life led to peripheral nerve sensitization, chronic visceral pain and alteration in gut microbiota distribution. Based on our preliminary work, the present project aims to study the effect of intestinal flora disorder on the gut-brain axis function and to verify roles of central nervous system - anterior cingulate cortex (ACC) and the basal lateral amygdala (BLA) neural circuitry in the development and maintenance of chronic visceral pain induced by neonatal chronic stress or colonic inflammation. This project will also investigate the roles of DNA methylation and demethylation homeostasis, which is induced by the environment-gene interactions, in controlling the structure and function of neural circuitry of the central nervous system. Through the implementation of this project, we will try to define the bidirectional regulation of the GBA and BGA homeostasis between functional gastrointestinal diseases and central nerve sensitization. In particular, we will try to unveil the mechanisms by which gut microbiota affects the gut-brain axis in modulation of chronic visceral hypersensitivity induced by neonatal adverse environmental stimulation. The long-term goal is to develop novel drugs to relieve chronic pain by targeting the intestinal flora and related brain areas, which might lay the foundation for further research of translational medicine.