Plant chemistry and microbes as drivers of microbiome-mediated resistance to parasitism in a butterfly herbivore

地球上的大多数动物都是食草动物，以植物为食物。植物已经进化出各种各样的有毒化学物质来保护自己不被吃掉。作为回报，许多食草动物已经进化出对毒素的抵抗力，有些甚至能够使用植物毒素来保护自己免受自己的敌人，包括捕食者和寄生虫。帝王蝶就是这样一种食草动物，它的幼虫以马利筋为食，马利筋中含有一种叫做强心草内酯的毒素。先前的研究表明，帝王蝶不仅将有毒的马利筋作为食物，还将其作为对抗衰弱寄生虫的药物。然而，仍然不清楚Cardenolides是否直接杀死寄生虫，或者它们是否改变了帝王蝶肠道微生物组（形成昆虫肠道植物群的所有微生物），以便特定的细菌或真菌杀死寄生虫。在这个项目中，研究人员将进行一系列实验，以找出有毒的乳草如何为帝王蝶提供药物。他们的毒素像毒品一样吗？它们会使肠道植物群不适合寄生虫吗？还是乳草本身为帝王蝶提供了益生菌，使它们能够抵御感染？作为研究的一部分，研究人员将培训博士后和本科生，并与亚特兰大的Fernbank科学中心合作，为五年级的公立学校学生制定课程计划。课程计划将集中在饮食如何改变动物肠道植物群，从而改变对疾病的易感性。鉴于许多动物肠道微生物群落和疾病病理的复杂性质，实验验证饮食质量、肠道群落组成和传染病之间的间接联系已被证明具有挑战性。在这个项目中，研究人员将利用帝王蝶及其原生动物寄生虫作为宿主-寄生虫相互作用的焦点，以研究宿主植物化学物质与微生物、食草动物肠道微生物组和寄生虫抗性之间的相互作用。该项目提供了一个理想的机会，将这些相互关联的宿主生态与疾病结果完全联系起来。在测试这些预测时，该提案还将扩大我们对药物代谢物如何与“益生菌”肠道微生物群落相互作用以影响感染的理解。研究人员将致力于以下具体目标：（1）确定植物化学和植物微生物在塑造肠道微生物群落向抗寄生虫状态组装中的作用;（2）确定微生物群落的关键特征，这些特征对肠道微生物保护免受寄生虫感染至关重要;（3）确定肠道微生物群落的空间和化学属性在多大程度上提高了对寄生虫的抵抗力。在初步结果的基础上，研究人员预测：（i）由于有毒次级代谢产物和植物微生物的高度多样性，选择了更多样化的肠道微生物群落;以及（ii）一个更加多样化的微生物群落通过寄生虫的物理和化学干扰为宿主提供了免受感染的保护。该奖项反映了NSF的法定使命，并通过使用基金会的学术价值和更广泛的影响审查标准。

Most animals on our planet are herbivores, using plants as their food. Plants have evolved a wide variety of toxic chemicals to protect themselves from being eaten. In return, many herbivores have evolved resistance to toxins, and some are even able to use plant toxins to protect themselves against their own enemies, including predators and parasites. One such herbivore is the monarch butterfly, whose caterpillars feed on milkweeds, which contain toxins called cardenolides. Previous work has shown that monarchs do not only use toxic milkweed as food, but also as medicine against a debilitating parasite. However, it remains unknown whether cardenolides directly kill parasites, or whether they change the monarch gut microbiome (all the micro-organisms that form the insect’s gut flora) so that specific bacteria or fungi kill the parasite. In this project, the researchers will carry out a series of experiments to find out how toxic milkweeds provide medicine to monarch butterflies. Do their toxins act like drugs? Do they make the gut flora inhospitable to parasites? Or do the milkweeds themselves provide probiotic bacteria to the monarch so they can withstand infection? As part of the research, the researchers will train a postdoc and undergraduate students, and work with the Fernbank Science Center in Atlanta to develop lesson plans for fifth grade public school students. Lesson plans will focus on the question how diet can change the gut flora of animals and thereby change susceptibility to disease. Experimentally validating the indirect link between diet quality, gut community composition, and infectious disease has proven challenging given the complex nature of many animal gut microbial communities and disease pathologies. In this project, the researchers will use monarch butterflies and their protozoan parasites as a focal host-parasite interaction to investigate the interplay between host plant chemicals and microbes, herbivore gut microbiomes and parasite resistance. This project provides an ideal opportunity to fully connect these interrelated pieces of host ecology to disease outcomes. In testing these predictions, the proposal will also expand our understanding of how medicinal metabolites interact with “probiotic” gut microbial communities to influence infection. The researchers will address the following specific aims: (1) Determine the role of phytochemistry and plant microbes in shaping the assembly of gut microbial communities towards an anti-parasitic state; (2) identify key traits of the microbial communities that are critical to gut microbial protection against parasitic infection; (3) determine the extent to which spatial and chemical attributes of gut microbial communities increase resistance to parasitism. Building upon preliminary results, the researchers predict that: (i) ingesting a high diversity of toxic secondary metabolites and plant microbes selects for a more diverse gut microbial community; and (ii) a more diverse microbial community provides hosts protection from infection through both physical and chemical interference of parasites.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.