Role of gut microbiota in intestinal inflammation caused by Toxoplasma gondii infection

Toxoplasma gondii can infect all warm blooded animals, causing severe zoonoticdiseases. At present, there is lack of safe and effective anti Toxoplasma drug.Oral infection of cysts is the main transmission route of Toxoplasma and cystsinfection will significantly alter the gut microbiota of host, which in turn willaffect the process of Toxoplasma infection. Recent studies have shown that the use of probiotics can effectively cure T. gondii infection. However, the currentresearch on the excavation and mechanism of anti Toxoplasma gut microbiota isquite limited. In our previous study, it was found that the severity of avirulent knockout and ME49 cyst infection was closely related to the gut microbiota by fecal transplantation. In addition, mice transplanted with the feces of mice infected with knockout cysts can resist Toxoplasma infection. Accordingly,we speculate that there may exist anti Toxoplasma gut microbiota in mice infectedwith knockout cysts. This project intends to further analyze and identify the gutmicrobiota associated with avirulent knockout cyst infection using a multi omicsapproach combining 16S rRNA genome, metagenomic and metabolomics. And we also try to elucidate the influence and mechanism of gut microbiota on T. gondii infection, which will provide important guiding significance for the development the drugs of anti Toxoplasma infection.

刚地弓形虫（Toxoplasma gondii）可感染所有温血动物，引发严重的人兽共患病。目前尚无安全有效的抗弓形虫药物。经囊胞的口部感染是弓形虫的主要传播途径，而囊胞感染会显著改变宿主肠道菌群，进而影响弓形虫的感染进程。近期研究显示，使用益生菌可有效治愈弓形虫感染，但当前针对抗弓形虫肠道菌群的挖掘及其作用机制的研究仍相当有限。我们前期研究通过粪便移植实验发现，无毒株敲除囊胞与ME49囊胞的感染严重程度与肠道菌群密切相关；此外，移植了敲除囊胞感染小鼠粪便的小鼠可抵抗弓形虫感染。据此我们推测，在敲除囊胞感染的小鼠体内可能存在抗弓形虫的肠道菌群。本项目拟采用结合16S rRNA基因组、宏基因组学与代谢组学的多组学方法，进一步分析并鉴定与无毒株敲除囊胞感染相关的肠道菌群，并尝试阐明肠道菌群对弓形虫感染的影响及其作用机制，这将为抗弓形虫感染药物的研发提供重要的指导意义。