外源核苷酸介导肠道菌群调控鱼类脂代谢分子机制研究

Dietary nucleotides can promote growth and enhance immunity in fish, which is one of the most promising alternatives for feed antibiotics in aquaculture. Previous studies have found that the nucleotide can promote growth through intestinal microbiota-mediated reducing standard metabolism of host. Moreover, intestinal microbiota regulate the lipid metabolism of fish. However, the molecular mechanism of intestinal microbiota-mediated regulation of fish lipid metabolism by exogenous nucleotides are not clear. This project is based on the zebrafish model to further verify the effect of exogenous nucleotides mediated intestinal microbiota on lipid metabolism in fish, the germ-free zebrafish model and morpholino gene knock down technology were used for analysis the effects of commensal bacteria and symbol strains on fish lipid metabolism related gene expression, explore exogenous nucleotides mediated intestinal bacteria regulate the pathway of lipid metabolism in fish, which reveals the exogenous nucleotide mediated molecular mechanism of intestinal microbiota regulation of lipid metabolism in fish. The results of this study will further clarify the growth promoting mechanism of exogenous nucleotides in fish, and drive the development and application of the regulation theory in fish digestive tract microbiota.

鱼类饲喂核苷酸表现促生长和增免疫效应，目前是水产养殖饲用抗生素的强有力替代品之一。申请人前期研究发现核苷酸通过肠道菌群下调宿主标准代谢促进鱼体生长，而且发现肠道菌群介导调控鱼体脂代谢。然而，外源核苷酸介导肠道菌群调控鱼类脂代谢的分子机制并不清楚。本项目以斑马鱼为模型，拟在进一步验证外源核苷酸介导肠道菌群影响鱼类脂代谢的基础上，结合无菌鱼模型和Morpholino基因敲降等技术平台，分析供体菌群及标志菌株对鱼体脂代谢相关基因表达的影响，探究外源核苷酸介导肠道菌群调控鱼类脂代谢路通，进而揭示外源核苷酸介导肠道菌群调控鱼类脂代谢的分子机制。该研究结果，将从肠道菌群角度深入阐明外源核苷酸对鱼类促生长机制，推进鱼类消化道菌群调控理论的发展与应用。

鱼类饲喂核苷酸表现促生长和增免疫效应，目前是水产养殖饲用抗生素的强有力替代品之一。前期研究发现核苷酸通过肠道菌群下调宿主标准代谢促进鱼体生长，而且发现肠道菌群介导调控鱼体脂代谢。然而，外源核苷酸介导肠道菌群调控鱼类脂代谢的分子机制并不清楚。.本项目以斑马鱼为模型进一步验证外源核苷酸介导肠道菌群影响鱼类脂代谢的基础上，结合无菌鱼模型和肠道菌群移植等技术方法，分析供体菌群及标志菌株对鱼体脂代谢相关基因表达的影响。研究结果表明，饲料中添加0.1%的外源核苷酸可降低斑马鱼肝脏脂肪含量，而增加肌肉组织的脂肪蓄积；通过组织切片观察和脂肪代谢相关基因检测均验证了上述表型；同时，0.1%的外源核苷酸改变斑马鱼肠道菌群丰度；通过无菌斑马鱼和肠道菌群移植方法并结合分子水平检测发现，外源核苷酸介导的肠道菌群可调控斑马鱼脂肪代谢；另外，对主要标志菌株的Cetobacterium somerae进行了无菌斑马鱼脂代谢基因检测发现，该菌株可下调斑马鱼Fiaf基因的表达，然而对脂肪代谢相关基因表达无显著影响，后续需进一步研究。.本研究通过对外源核苷酸介导肠道菌群调控鱼类脂代谢路通的分析，揭示了外源核苷酸介导肠道菌群调控鱼类脂代谢的分子机制。该研究结果，从肠道菌群角度深入阐明外源核苷酸对鱼类促生长机制，对水产养殖中鱼类营养型脂肪肝的预防和调控提供了新的思路。