赭曲霉毒素A（OTA），具有肠毒性，可能通过母体效应导致子代肠道损伤。我们前期的研究结果发现，OTA可改变肠道微生物的组成比例，激活TLR4信号通路，破坏肠道屏障。肠道微生物对TLR4启动子区甲基化起着关键调控作用，肠道微生物介导的甲基化是否介导OTA导致的肠道损伤仍需研究。因此，本项目选取对OTA最为敏感的鸭作为试验对象，采用母代自然饲喂、胚蛋注射、子代饲养等方式，分别研究OTA在胚胎组织中的沉积规律、母源OTA对胚胎及子代肠道屏障的影响、TLR4通路在OTA致鸭胚肠道损伤中所起的作用以及肠道微生物介导的TLR4甲基化在OTA致鸭肠道损伤中的作用。项目旨在阐明肠道微生物介导的TLR4甲基化在母源性OTA致鸭胚及子代肠道损伤的分子机制，以期在霉菌毒素污染情况下，以母代营养为靶点，通过调控肠道微生物或者肠道完整性，改善家禽肠道健康。

Ochratoxin A (OTA) is a widespread mycotoxin and induces intestinal injury to human and various species of animals. And OTA may lead intestinal injury in offspring due to the the maternal effect. Our previous studies presented that OTA treatment in ducks altered the intestinal microbiota composition and structure, induced the accumulation of LPS and activited the TLR4 signaling pathway, and destroy the intestinal injury. The intestinal microbiota has critical importance in methylation of TLR4 promoter. However, it remains to know whether intestinal microbiota mediates the methylation of TLR4 in intestinal injury induced by OTA. Here, the ducks most sensitive to OTA are selected as experimental animals in this project. Natural feeding was carried out to study the deposition of OTA in embryonic tissue and the effect of maternal OTA on the intestinal barrier function of embryo and offspring. The role of TLR4 signaling pathway in OTA induced intestinal injury of duck embryo were studied by embryo egg injection. The effect of intestinal microbial mediated TLR4 methylation on OTA induced intestinal injury in duck embryo was studied by means of embryo egg injection and intestinal microbial clearance of offspring. The aim of this project is to elucidate the molecular mechanism of intestinal tract damage induced by maternal ochratoxin A in duck embryo and offspring and explore effective measures to alleviate the intestinal toxicity of OTA by targetting to the marternal nutrition through regulating the intestinal microbiota or preserving intestinal integrity, in case of mycotoxin pollution.