低聚木糖干预沙门氏菌粘附素和侵袭素表达抑制鸡肠黏膜损伤的机制

Chicken paratyphoid, a serious threat to bird septic infection is caused by Typhimurium. Our preliminary study showed that xylo-oligosaccharides regulate the expression of genes associated with adhesion and colonization of Salmonella, and effectively inhibit the damage of intestinal epithelial cells from bacterial. This project intends to isolate adhesin and invasive factors and screen key factors to construct Salmonella key adhesins and attenuated variants of Salmonella attacking enterocytes and SPF chickens. The key adhesion proteins and invasive elements of Salmonella and their pathogenic mechanisms were identified through the measurement of intestinal mucosal injury, metabolomics and immunological analysis. Xylo-oligosaccharide interferes with Salmonella proliferation, metabolism and the expression of virulence factors by metabolome and transcriptome studying on the expression and mechanism of xylo-oligosaccharides interfering with adhesion and invasive factors. Adhesins, invasive factors and their attenuated variants infect on chicken epithelial cells and SPF chickens. By testing the effects of cell and intestinal mucosal damage, and using metabolome and immunological assays to determine the differential expression of metabolic factors and immune factors associated with cell and intestinal mucosal damage, the host metabolism and immune mechanisms of chicken intestinal epithelial cells and mucosal lesions will be analyzed. The mechanism on xylo-oligosaccharides was based on the intervention of Salmonella adhesion and invasion to protect intestinal mucosa from injuring in chickens. This research has important academic value and practical significance for analysis of the mechanism of xylo-oligosaccharides in inhibiting the risk of Salmonella.

鸡副伤寒是鼠伤寒沙门氏菌引起、以肠炎和败血性为病症的传染病。项目组前期研究发现，低聚木糖调控与沙门氏菌粘附和定植肠黏膜相关基因表达，实现其对肠黏膜损伤的抑制。项目分离粘附素和侵袭素，筛选关键因子，构建鼠伤寒沙门氏菌关键粘附素和侵袭素减毒变异株，粘附素、侵袭素及减毒株攻毒肠上皮细胞和SPF鸡，通过肠黏膜损伤、代谢组和免疫组测定明确沙门氏菌关键粘附素和侵袭素及其致病机制。低聚木糖处理沙门氏菌，粘附素和侵袭素测定，代谢组和转录组研究低聚木糖干预粘附素和侵袭素表达及其机制；低聚木糖处理的沙门氏菌及其粘附素与侵袭素感染肠上皮细胞和SPF鸡，细胞和肠黏膜损伤效应测定，代谢组和免疫组测定细胞和肠黏膜损伤相关代谢因子和免疫因子差异表达，分析其损伤干预机制，解析低聚木糖干预沙门氏菌粘附素和侵袭素表达抑制鸡肠黏膜损伤的机制。研究结果对明确低聚木糖抑制沙门氏菌危害作用、解析其机制具有重要的学术价值和应用前景。

鸡副伤寒是鼠伤寒沙门氏菌引起，以肠炎和败血等为病症的传染病，呈世界性分布，死亡率可达10%-50%。低聚木糖调控与沙门氏菌粘附和定植肠黏膜相关基因表达，表现出肠黏膜损伤的抑制作用。为明确作用、解析机制，提升营养手段干预鸡鼠伤寒沙门氏菌疾病的效果，项目主要开展了以下几个方面的研究工作：（1）HtpG蛋白促进宿主NF-κB信号通路激活，刺激宿主肠上皮细胞炎症的发生，增加鼠伤寒沙门氏菌的感染效果； wzzE基因的缺失可导致其黏附、侵袭能力下降，但不会链式诱导肠道细胞炎症发生、破坏肠道屏障的降低；STM0306基因与细菌黏附、侵袭、促炎能力及致病能力相关，能够激活NF-κB信号通路并导致多种细胞炎症因子的表达。（2）不同聚合度的低聚木糖对鼠伤寒沙门氏菌增殖影响程度不同，它们均降低鼠伤寒沙门氏菌对肠道上皮细胞粘附，以木糖效果最显著，其次是木五糖和木六糖，木糖能显著抑制沙门氏菌增殖与粘附道上皮细胞，降低细胞的损伤，组学分析推测可能是通过改变其生长、粘附相关基因galk、speA、smpB表达来实现。另外，低聚木糖对鼠伤寒沙门氏菌碳水化合物、氨基酸的转运代谢相关基因有显著影响。木六糖可能通过靶向鼠伤寒沙门氏菌HtpG，下调鞭毛装配和感染等相关基因的表达，导致其运动性能力、生物被膜形成能力和黏附侵袭能力下降；低聚木糖复合物可能通过抑制鼠伤寒沙门氏菌STM0306表达，降低其生物被膜形成能力、黏附侵袭能力、细胞内增殖能力、促炎能力及致病能力（3）AHLase可通过改善免疫性能、肠道屏障和肠道菌群结构，提高感染鼠伤寒沙门氏菌后肉仔鸡的生长性能。项目研究的科学意义在于：（1）进一步补充沙门氏菌损伤鸡肠黏膜的机制。（2）初步建立低聚木糖干预沙门氏菌粘附素和侵袭素表达抑制鸡肠黏膜损伤的科学理论基础。科学理论的建立为提高肉鸡健康养殖效率、基于低聚木糖开发控制沙门氏菌危害的营养手段，展现了很好的应用前景。

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