The microbiome of the helminth infected host: Implications for immunity and intestinal homeostasis

寄生虫(蠕虫)能够感染包括人类在内的多种动物的胃肠道。蠕虫感染通常与对受感染个体宿主的健康有显著影响有关。这种寄生虫的一个例子是感染全球10亿人的人类鞭虫。在小鼠体内存在一个类似的模型系统，它允许我们研究鞭虫与宿主-S免疫系统之间的相互作用，并了解宿主试图根除蠕虫的机制。鞭虫在大肠的感染部位是宿主S肠道菌群的栖息地，这些细菌对宿主S免疫反应的发育和维持以及对复杂膳食分子的消化都有重要作用。我们有数据表明，在小鼠慢性鞭虫感染中，受感染动物的肠道菌群发生了戏剧性的变化。在这项研究中，我们的目标是准确地定义鞭虫感染后肠道菌群的这些变化，然后了解这些变化对宿主的功能影响。具体地说，肠道菌群的变化是否为肠道中的新生态系统提供了更有利于蠕虫长期生存的生态系统？它们是否会损害感染者消化复杂碳水化合物的能力，从而导致长期的减肥？最后，肠道菌群的这些变化是否会对我们进行免疫反应的方式产生影响，例如对其他感染源的免疫反应，或者对自身免疫或过敏等免疫疾病的影响。

Worm parasites (helminthes) are capable of infecting the gastrointestinal tract of a broad range of animals including humans. Helminth infection is often associated with pronounced effects on the health of the infected individual host. An example of such a parasite is the human whipworm that infects 1 billion people worldwide. An analogous model system exists in the mouse that allows us to study the interaction between the whipworm and the host?s immune system and understand the mechanisms by which the host attempts to eradicate the worm. The site of whipworm infection in the large intestine is home to the host?s gut flora, these bacteria are important in the development and maintenance of the host?s immune response and in digesting complex dietary molecules. We have data showing that in a chronic whipworm infection in the mouse there are dramatic changes in the gut flora of the infected animal. In this research we aim to precisely define these changes in the gut flora following whipworm infection and then to understand the functional implications to the host as a result of these changes. Specifically, do the changes in gut flora provide a new ecosystem in the gut more beneficial to long term worm survival? Do they compromise the ability of the infected individual to digest complex carbohydrates thereby leading to long-term weight loss? Finally, do these changes in gut flora have implications on the way we mount immune responses e.g. to other infectious agents or in terms of immune disease such as autoimmunity or allergy.