Intestinal microbiome modulation by roundworms and consequences for the metabolome

蛔虫对肠道微生物组的调节及其对代谢组的影响

• 批准号: 421365943
• 负责人: Professorin Dr. Christina Strube, Ph.D.
• 金额: --
• 依托单位: Institut für Parasitologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/421365943?language=en
• 关键词: Intestinal; microbiome; modulation; roundworms; consequences

Infections with the closely related roundworms Ascaris lumbricoides and Ascaris suum, respectively, are of considerable importance for human as well as porcine health. These infections lead to nutrient deficiency, probably caused primarily by an impairment of the intestinal nutrient transport. Nevertheless, the intestinal microbiota may also contribute to metabolic deficiencies. Since roundworms and the intestinal microbiota share the same ecological niche, it seems obvious that they exert influences on each other. An effect of nematode infections on the intestinal microbiota has already been shown in several studies in humans as well as in animals. Preliminary insights regarding A. suum infections in swine exist; however, these are limited to microbial alterations in the proximal colon, which were studied at two time points post infection only. Insights regarding the influence of human A. lumbricoides infections on the intestinal microbiota are limited to faecal samples, which only allow drawing conclusions regarding processes in the distal parts of the large intestine. Furthermore, so far no knowledge exists regarding the parasitic life stages and products which may influence the microbiota, as well as regarding the question whether a single infection has the same effect as a more natural, repeated exposure. Thus, the aim of this study is a comprehensive characterization of the microbial alterations in different intestinal compartments over the course of the A. suum infection in pigs. To this end, the study will take advantage of several experiments which will be carried out in the frame of a project analyzing the intestinal nutrient transport in A. suum-infected pigs. In addition to the analysis of weekly faecal samples, the dissection of one infection group each at three defined time points post infection also allows analysing the microbiota in different intestinal compartments. To additionally draw conclusions regarding functional aspects of the microbiota, corresponding samples of intestinal content as well as serum samples will also be analysed with regard to the metabolome. The question whether a single infection with A. suum eggs has comparable effects to a continuous exposure will be answered in another experiment. Finally, the planned project will offer insights regarding the question whether only the contact with adult roundworms or their excretory-secretory or somatic antigens, respectively, may be causative for the observed effects. In combination with a current project on the intestinal nutrient transport, this research proposal allows a comprehensive characterization of the parasite-microbiota-host relationship which can be regarded as causative for the nutrient deficiencies in the course of porcine as well as human ascariosis.

感染关系密切的蛔虫分别是蛔虫和猪蛔虫，对人类和猪的健康都有相当重要的意义。这些感染导致营养缺乏，可能主要是由于肠道营养物质运输的障碍造成的。然而，肠道微生物区系也可能导致代谢缺陷。由于蛔虫和肠道微生物区系共享相同的生态位，显然它们相互影响。线虫感染对肠道微生物区系的影响已经在人类和动物的几项研究中得到证明。关于猪的猪链霉菌感染的初步认识是存在的；然而，这些认识仅限于近端结肠的微生物改变，仅在感染后的两个时间点进行了研究。关于人类蛔虫感染对肠道微生物区系影响的见解仅限于粪便样本，这些样本只允许得出关于大肠末端过程的结论。此外，到目前为止，还没有关于寄生生活阶段和可能影响微生物区系的产品的知识，以及关于单一感染是否与更自然的反复暴露具有相同效果的问题。因此，这项研究的目的是全面描述猪链霉菌感染过程中不同肠室的微生物变化。为此，本研究将利用将在一个分析感染猪链霉菌的猪的肠道养分运输的项目框架内进行的几个实验。除了每周对粪便样本进行分析外，在感染后的三个特定时间点对每个感染组进行解剖也可以分析不同肠道间的微生物区系。此外，为了得出关于微生物区系功能方面的结论，还将分析相应的肠道内容物样本以及血清样本的代谢物。一次感染猪链霉卵是否具有与持续接触类似的效果的问题将在另一项实验中得到解答。最后，计划中的项目将提供关于以下问题的见解：是否只有与成虫或它们的排泄物分泌或体细胞抗原的接触可能是观察到的影响的原因。结合目前一个有关肠道营养物质转运的项目，这项研究建议可以全面描述寄生虫-微生物-宿主之间的关系，这种关系可以被认为是导致猪和人类蛔虫病过程中营养缺乏的原因。