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身体活动的变化如何影响哺乳动物模式生物（如大鼠和小鼠）的新陈代谢。虽然已知这两个因素是重要的，但关于其他可能导致或促成代谢疾病的条件的信息很少。可患代谢性疾病的动物种类也不清楚。研究人员最近证明，糖尿病和肥胖并不是哺乳动物所特有的，它们在蜻蜓的自然种群中也会发生，这是一种原生动物寄生虫肠道感染的结果。初步数据表明，蜻蜓所栖息的水体的酸度水平是蜻蜓感染率的一个强有力的预测指标，因此，蜻蜓物种的代谢疾病。在任何动物系统中，感染在代谢性疾病发展中的作用都知之甚少。该项目提供了一个独特的机会，提供新的生态和生理见解，并将允许对这一问题进行深入研究。该综合项目将通过实验将水酸度、蜻蜓肠道微生物组成和寄生虫感染易感性的自然变化与蜻蜓的代谢和其他性能表型联系起来。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）和对人类具有经济重要性的物种（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，感染在代谢性疾病（如肥胖）发展中的致病作用都知之甚少。该项目建议开展实验，以扩展先前对这种蜻蜓宿主-寄生虫相互作用的研究，并为昆虫感染相关代谢疾病的生态生理学提供新的见解。基于该系统的新的生态和生理数据，这些研究将检验环境pH和寄生虫与肠道微生物群的化学相互作用是蜻蜓宿主对感染易感性的重要驱动因素，并将其升级为代谢性疾病和适应性降低。研究者将1)使用全因子处理设计来检查环境（水）pH值和暴露于感染性孢子对幼虫和宿主肠道微生物组组成和寄生虫负荷的影响，2)确定感染对飞行肌肉性能和高强度飞行行为期间燃料使用的影响（现场高速摄像、原位工作回路和呼吸商测定）。3)通过检查健康和受感染成人的全身免疫，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.