Collaborative Research: Linking Causes of Variation in the Amphibian Skin Microbiome with Consequences for Disease Risk

动物体内和体表都有微生物群落（细菌、病毒、真菌）。这些微生物群落被称为共生微生物群落或微生物组。共生微生物群落越来越被认为是人类和动物健康的重要参与者。共生微生物可能通过影响宿主对致病生物体（病原体）的反应而对动物（宿主）健康很重要。该项目旨在了解微生物组如何影响抗病性，同时研究壶菌病，这是一种由病原体Batrachochytrium dendrobatium（缩写为Bd）引起的两栖动物（青蛙，蟾蜍和蝾螈）的毁灭性疾病。Bd是一种感染两栖动物皮肤的真菌，可导致潜在致命的壶菌病。内华达州黄腿蛙（Rana sierleg）正处于灭绝的危险之中，Bd是对这种蛙最严重的威胁之一。Bd已经导致了整个R种群的大规模死亡。先生然而，某些种群的R. Serratis似乎对致死性壶菌病有一定抗性。了解为什么这些耐药种群能够生存，尽管Bd感染可能是至关重要的努力，以保护物种。皮肤微生物组可能有助于抵抗疾病，但缺乏确切的证据。本研究将探讨三个核心问题：（1）R。皮肤微生物群有助于抵抗疾病？(2)微生物组组成（即，组成微生物组的微生物物种）影响微生物组的稳定性，当青蛙感染Bd？这对于理解当宿主受到传染病威胁时微生物组的持续功能可能很重要。(3)宿主和环境差异如何影响微生物组组装？换句话说，是什么力量导致不同青蛙或种群的微生物组差异，或者在不同时间的单个青蛙中？这可能揭示了形成归因于微生物组的功能变异的根本原因，例如抗病性的差异。总之，这项工作将促进对宿主和环境如何决定微生物组组成的理解，以及这反过来又如何塑造微生物组功能和稳定性。了解这些过程是相关的战略，保护受威胁的两栖动物。更广泛地说，理解R。共生微生物群落与Bd相互作用的研究可以为了解微生物-病原体相互作用以及其他动物和人类的传染病管理提供新的视角。共生微生物群落越来越被认为是多细胞生物发育和健康的重要角色。一些研究发现，由病原微生物引起的疾病与宿主微生物组的组成与健康个体的微生物相比较的变化有关，但通常很难确定因果关系：观察到的相关性可能表明特定的微生物组组合赋予抗病性，或者病原体感染破坏和改变了微生物组。 该项目旨在了解两栖动物皮肤相关细菌群落（皮肤微生物组）在介导对真菌病原体Batrachochytrium dendrobatim的抗性中的作用。该项目将测试抗病和易感宿主之间是否存在微生物组差异，暗示自然界中的保护作用。 重要的是，这项工作将通过测试微生物组的实验性改变是否会导致抗病性的变化，或者病原体感染是否会改变微生物组，进一步阐明病原体和微生物组之间的因果关系。这项研究还旨在了解是什么决定了微生物组的系统发育和功能组成，这是了解微生物组相关抗病差异的根本问题。 现场调查将用于量化宿主遗传变异和环境因素与野生青蛙皮肤微生物组的系统发育和功能组成相关的程度，而实验操作将清楚地显示这些关系中的因果关系。 将开发数学模型，以确定潜在驱动微生物群落组成变化的生态机制。 最后，将开发干扰条件下（如病原体感染）微生物群落动态的预测模型，整合群落组装和抗病性概念。

Animals have communities of microbes (bacteria, viruses, fungi) living in and on their bodies. These microbial communities are referred to as symbiotic microbial communities, or the microbiome. Symbiotic microbial communities are increasingly recognized as important players in the health of humans and animals. Symbiotic microbes may be important to animal (host) health by affecting host response to disease-causing organisms (pathogens). This project aims to understand how the microbiome affects disease resistance while studying chytridiomycosis, a devastating disease of amphibians (frogs, toads and salamanders) caused by the pathogen Batrachochytrium dendrobatidis (abbreviated Bd). Bd is a fungus that infects the skin of amphibians and can cause potentially-lethal chytridiomycosis. The Sierra Nevada yellow-legged frog (Rana sierrae) is in danger of extinction and Bd is one of the most serious threats to this frog. Bd has caused massive die-offs of entire populations of R. sierrae. However, certain populations of R. sierrae appear to be somewhat resistant to lethal chytridiomycosis. Understanding why these resistant populations are able to survive despite Bd infection may be critical for efforts to conserve the species. It is possible that the skin microbiome contributes to disease resistance, however definitive evidence is lacking. This project will address three core questions: (1) To what extent does the R. sierrae skin microbiome contribute to disease resistance? (2) Does microbiome composition (i.e., the microbial species that make up the microbiome) affect the stability of the microbiome when frogs become infected with Bd? This may be important to understanding continued functionality of the microbiome when the host is threatened by infectious diseases. (3) How do host and environmental differences affect microbiome assembly? In other words, what are the forces that lead to differences in the microbiome of different frogs or populations, or within an individual frog at different times? This may reveal underlying causes that shape functional variation attributed to the microbiome, such as differences in disease resistance. In summary, this work will advance understanding of how host and environment determine microbiome composition and how this in turn may shape microbiome function and stability. Understanding of these processes is relevant to strategies for protecting threatened amphibians. More broadly, understanding how the R. sierrae microbiome interacts with Bd can provide insights into microbiome-pathogen interactions and management of infectious disease in other animals and humans.Symbiotic microbial communities are increasingly recognized as important players in the development and health of multicellular organisms. Several studies have found that disease caused by pathogenic microbes is associated with changes in the composition of the microbiome of the host compared with the microflora of healthy individuals, but it has often been difficult to determine cause and effect: the observed correlation may indicate that particular microbiome assemblages confer disease resistance, or that pathogen infection disrupts and alters the microbiome. This project aims to understand the role of the amphibian skin-associated bacterial community (skin microbiome) in mediating resistance to the fungal pathogen Batrachochytrium dendrobatidis. The project will test if microbiome differences exist between disease-resistant and -susceptible hosts, suggestive of a protective role in nature. Importantly, this work will further clarify the causal relationship between pathogen and microbiome by testing if experimental alteration of the microbiome leads to changes in disease resistance, or if instead pathogen infection alters the microbiome. This study also aims to understand what determines the phylogenetic and functional composition of the microbiome, a question that is fundamental to understanding the root of microbiome-associated differences in disease resistance. Field surveys will be used to quantify the degree to which host genetic variation and environmental factors are associated with the phylogenetic and functional composition of the skin microbiome sampled from wild frogs, while experimental manipulations will clearly show cause and effect in these relationships. Mathematical models will be developed to identify ecological mechanisms that potentially drive variation in microbial community composition. Finally, predictive models of microbial community dynamics under conditions of disturbance (such as pathogen infection) will be developed, integrating community assembly and disease resistance concepts.