慢性应激状态下肠菌Fusobacterium nucleatum与claudin-2互作致微肠漏的机制研究

批准号:
82000487
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
罗清清
依托单位:
学科分类:
消化道内环境紊乱、黏膜屏障障碍及相关疾病
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
罗清清
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中文摘要
微“肠漏”是肠黏膜屏障障碍,致腔内有害因素侵袭,引发各类肠病的关键病生环节。研究证实应激是微“肠漏”的触发因素。但具体机制不明。我们的预实验发现慢性应激大鼠:①迷走神经主导的肠黏膜上皮细胞M受体乙酰胆碱(ACh)的效应下调;伴随②黏液质和量改变、粪便中Fusobacterium nucleatum (F. nucleatum)丰度增加;和③上皮细胞促“漏”蛋白claudin-2高表达。故推测:慢性应激致迷走在肠黏膜上皮细胞M受体作用下调,黏膜屏障削弱,使F. nucleatum定殖增加,固有淋巴细胞ILC2产生IL-13增加,进而诱导促“漏”蛋白claudin-2高表达。本项目拟阐明应激-肠上皮迷走胆碱能M受体联动的条件致病菌F. nucleatum-IL-13- claudin-2与微“肠漏”的恶性循环机制细节。项目将对应激致“肠漏综合征”相关临床问题的理解和干预提供新思路。
英文摘要
Micro-leaky gut is the key pathophysiological process of functional and mechanical bowel diseases with compromised mucosal barrier and enhanced invasion of deterious factors. Researches have proven that stress is an important trigger of micro-leaky gut. However, the specific mechanism hasn’t been demonstrated yet. Our preliminary experiments revealed that in chronic stressed rats, i) the effect of acetylcholine of vagus nerve on muscarinic acetylcholine receptors (mAChRs) of intestinal epithelial cells decreased; accompanied by ii) altered amount as well as the content of the mucus and increased abundance of Fusobacterium nucleatum (F. nucleatum) in the feces; and iii) up-regulated expression of claudin-2, a pro-leaky protein, in the epithelial cells. Thus, we postulated that under chronic stress the compromised effect of vagus nerve on mAChR led to impaired mucosal barrier. The dysfunction of mucosal barrier caused expanded colonization of F. nucleatum, which further activated the innate immune cell, ILC2, to synthesize IL-13. In turn, IL-13 promoted the expression of claudin-2. This project endeavors to demonstrate the concrete mechanisms of vicious circle of opportunistic pathogen F. nucleatum, IL-13, claudin-2 and micro-leaky gut, triggered by decreased effect of acetylcholine on mAChR under stress circumstance. Implementation of the project will provide with new idea of understandment and intervention of leaky gut syndrome associated clinical situation contributed by stress.
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专利列表
DOI:10.1111/nmo.14718
发表时间:2023-11-27
期刊:NEUROGASTROENTEROLOGY AND MOTILITY
影响因子:3.5
作者:Luo,Qing-Qing;Cheng,Li;Chen,Sheng-Liang
通讯作者:Chen,Sheng-Liang
DOI:10.1155/2022/7294775
发表时间:2022
期刊:Gastroenterology research and practice
影响因子:2
作者:
通讯作者:
国内基金
海外基金
