Ecophysiology of a host-parasite interaction that causes metabolic disease

人类和其他哺乳动物患上糖尿病和肥胖症等代谢性疾病的原因和速度是复杂的。传统上，生物医学研究的重点是饮食和体力活动的变化如何影响大鼠和小鼠等哺乳动物模式生物的新陈代谢。虽然这两个因素被认为是重要的，但关于其他可能导致或促成代谢性疾病的疾病的信息很少。可患代谢性疾病的动物物种范围也是未知的。研究人员最近证明，糖尿病和肥胖症并不是哺乳动物独有的，而是由于原生动物寄生虫的肠道感染而在自然蜻蜓种群中发生的。初步数据表明，蜻蜓栖息的水体中的酸度水平是感染几率的有力预测因素，因此，蜻蜓物种中的代谢性疾病。在任何动物系统中，对感染在代谢性疾病发展中的作用都知之甚少。这个项目代表着一个独特的机会，可以提供新的生态和生理见解，并将使对这个问题的深入研究成为可能。这个综合项目将实验地将水酸度、蜻蜓肠道微生物群组成和寄生感染敏感性与蜻蜓代谢和其他表现表型的自然变化联系起来。这项工作将强调环境因素对代谢性疾病的重要性。鉴于引起人类疾病(如疟疾、弓形虫病)和对人类具有重要经济价值的物种(如蜜蜂、大黄蜂)的自然昆虫-原生动物寄生虫相互作用日益普遍，该项目也具有广泛的相关性。在任何动物系统中，对感染在肥胖等代谢性疾病发展中的致病作用都知之甚少。该项目提议进行实验，以扩展之前关于蜻蜓宿主-寄生虫相互作用的工作，并为昆虫感染相关代谢疾病的生态生理学提供新的见解。基于来自该系统的新的生态和生理数据，这些研究将检验以下假设：环境pH以及寄生虫和肠道微生物群的化学相互作用是导致蜻蜓易受感染、升级为代谢性疾病和降低蜻蜓宿主适合度的重要驱动因素。研究人员将1)使用全因素方差处理设计，检查环境(水)pH和接触感染孢子对幼虫和宿主肠道微生物组成和寄生虫负载的影响，2)确定感染对高强度飞行行为中飞行肌肉性能和燃料使用的影响(现场高速摄像、原位工作环和呼吸商测定)，以及3)通过检查健康和受感染成年人的系统免疫力，对寄生虫排泄/分泌产物和热灭活细菌培养的反应，评估寄生虫操纵宿主的程度。

The causes and rates at which humans and other mammals develop metabolic diseases such as diabetes and obesity are complex. Biomedical research has traditionally focused on how shifts in diet and physical activity affect metabolism in mammalian model organisms such as rats and mice. While these two factors are known to be significant, there is very little information on other conditions that can cause or contribute to metabolic disease. The range of animal species that can develop metabolic disease is also unknown. The investigators recently demonstrated that diabetes and obesity are not unique to mammals and occur in natural populations of dragonflies as a consequence of gut infection by a protozoan parasite. Preliminary data indicate that the level of acidity in water bodies that dragonflies inhabit is a strong predictor of rates of infection and therefore, metabolic disease in the dragonfly species. The role of infection in the development of metabolic disease is poorly understood in any animal system. This project represents a unique opportunity to provide new ecological and physiological insights and will allow in-depth studies on this problem. This integrative project will experimentally link natural variation in water acidity, dragonfly gut microbiome composition and parasitic infection susceptibility to dragonfly metabolic and other performance phenotypes. This work will underline the importance of environmental factors to metabolic disease. This project also has broad relevance given the growing prevalence of natural insect-protozoan parasite interactions that cause disease in humans (e.g. malaria, toxoplasmosis) and in species of economic importance (e.g. honey bees, bumblebees) to humans. The causative role of infection in the development of metabolic disease such as obesity is poorly understood in any animal system. The project proposes to conduct experiments that will extend previous work on this dragonfly host-parasite interaction and provide novel insights into the ecophysiology of infection-related metabolic disease in an insect. Based on new ecological and physiological data from this system, these studies will examine the hypotheses that both environmental pH and chemical interactions of parasite and gut microbiota are important drivers of susceptibility to infection, and its escalation into metabolic disease and reduced fitness in the dragonfly host. The investigator will 1) use full factorial treatment designs to examine effects of environmental (water) pH and exposure to infectious spores on larval and host gut microbiome composition and parasite load, 2) determine infection effects on flight muscle performance and fuel use during high intensity flight behavior (field high speed videography, in situ work loop and respiratory quotient assays), and 3) assess the extent of host manipulation by the parasite through examination of systemic immunity in healthy and infected adults, in response to parasite excretory/secretory products and to heat-inactivated bacterial cultures.