一种潜在的人兽共患人五毛滴虫对小鼠肠道致病性研究

长期以来人五毛滴虫被认为是一种哺乳动物肠道的非致病性原虫。然而，越来越多的研究显示其可能是一种潜在的人兽共患病原。申请者前期研究率先发现人五毛滴虫感染与临床消化道肿瘤存在明显的相关性，但其原因不清楚。为此，本研究拟从人五毛滴虫对小鼠的感染性和致病性入手，确定人源人五毛滴虫对不同免疫状态小鼠的感染性和感染剂量，探究人五毛滴虫感染对不同免疫状态小鼠肠道黏膜组织以及细胞增生、凋亡和炎性细胞因子等变化的影响，明确人五毛滴虫感染是否引起肿瘤相关的病变。另外，通过对人五毛滴虫感染小鼠肠道黏膜组织转录组学分析与验证，观察人五毛滴虫感染小鼠肠道致病相关细胞信号通路的变化，以期揭示人五毛滴虫的致病性这一关键科学问题。本研究结果可为下一步深入研究人五毛滴虫与宿主以及消化道癌症的关系及其防控等提供重要的基础和前提。

Pentatrichomonas hominis has long been considered as a non-pathogenic protozoan in mammalian gut.However, more and more studies have shown that it may be a potential zoonotic pathogen.The applicant has first found out there was a significant correlation between Pentatrichomonas hominis infection and clinical digestive tract tumor in the previous study,but the reason was not clear.Therefore,this study will be started with the infectivity and pathogenicity of Pentatrichomonas hominis in mice.The infectivity and infective dose of Pentatrichomonas hominis in mice with different immune status will be determined.The effect of Pentatrichomonas hominis isolated from human on intestinal mucosa tissue and cell proliferation, apoptosis and inflammatory cytokines in mice with different immune status will be observed.And we will determine whether tumor related lesions could be caused by Pentatrichomonas hominis.In addition,we will investigate the changes of cellular signaling pathways related to intestinal pathogenicity in mice infected with Pentatrichomonas hominis by analyzing and verifying the transcriptome of intestinal mucosa tissue.And then it will be revealed the key question on pathogenicity of Pentatrichomonas hominis.The results of this study can provide important basis and premise for further study on the relationship between Pentatrichomonas hominis infection and host along with digestive tract cancer, as well as its prevention and control.