The wild mammalian microbiome

脊椎动物的肠道中充满了庞大而多样的细菌群落，它们的数量至少比宿主的细胞多一个数量级，即所谓的肠道微生物群。分子生物学的最新进展彻底改变了对这些细菌群落的研究，并证明了它们对宿主生物学、健康和疾病的普遍影响。与此同时，它们巨大的可变性已经被揭示出来——它们在物种之间、个体之间以及个体内部随着时间的推移而变化巨大。这种变化需要解释，但我们目前对生态和进化过程的理解仍然有限。这方面的一个关键障碍是，到目前为止，微生物群的研究主要集中在两种模式生物上——人类和实验室小鼠，这在自然脊椎动物种群中形成肠道微生物群落的知识方面留下了空白。我概述了一项研究计划，通过开发野生小型哺乳动物作为微生物群研究的新系统，并利用它们来解决我们目前知之甚少的几个关键问题：(1)为什么单个种群中的个体表现出不同的肠道微生物特征，以及随着时间的推移，是什么过程驱动了个体体内这些群落的变化？(2)肠道微生物和其他肠道微生物究竟是如何在种群内的宿主之间传播的——它们的社会互动或共同使用空间在这一过程中是否起着重要作用？(3)不同物种肠道菌群差异背后的生态和进化过程是什么？为了回答前两个问题，我将使用一种常见的英国啮齿动物——木鼠——作为模型研究系统。木鼠是这一目的的理想选择：在野外，大量的个体可以在一个相对较小的区域内进行独特的标记和监测，反复采样它们的肠道微生物群，并对它们的当地栖息地进行精细的描述。此外，在野外和圈养中都可以对这个物种进行操纵实验。为了解决第一个问题，我将结合详细的实地观察和对照实验来建立肠道微生物群落群体内变化形成过程的全面图景。关于关键假设因素的观察数据，包括遗传相关性、饮食、栖息地、肠道寄生虫、年龄和生殖状态，将使我能够估计它们对个体内部和个体之间微生物群变异的相对贡献。我还将在野生小鼠身上进行大规模药物治疗实验，直接测试另一组关键肠道居民——寄生蠕虫——的存在如何影响微生物群。最后，我将在圈养的木鼠身上进行“饮食转变”实验，以测试天然食物组的变化如何塑造肠道微生物群。为了解决第二个问题，我将在上述相同的野生木鼠种群中使用一种新颖的基于“社会网络”的方法，来研究动物的社会接触和空间使用如何驱动肠道微生物和肠道寄生虫的传播。最后，为了回答第三个问题，我将使用野生小型哺乳动物（老鼠、田鼠和鼩鼱）进行一项多物种研究，这些哺乳动物共同出现在欧洲几种不同的栖息地类型中。这项研究将首次测试宿主的进化遗产或其当前的环境条件（栖息地和饮食）是否在塑造其微生物群方面起主导作用。这项研究将为影响哺乳动物肠道微生物群的生态和进化过程提供基本见解，从而提高我们对这些对宿主健康至关重要的群落如何以及为什么在性质上发生变化的认识。它还将填补关于肠道生物如何在动物之间传播的知识方面的重要空白，这与传染病的控制有关。

The vertebrate gut teems with a vast, diverse community of bacteria that outnumber the cells of their host by at least an order of magnitude, the so-called gut microbiota. Recent advances in molecular biology have revolutionised research into these bacterial communities, and demonstrated their pervasive effects on host biology, health and disease. At the same time, their tremendous variability has come to light - they vary enormously across species, among individuals, and within individuals over time. Such variation demands an explanation, yet our current understanding of the ecological and evolutionary processes responsible remains limited. A key obstacle in this respect is that so far, microbiota research has focused heavily on just two model organisms - humans and laboratory mice, leaving a gap in knowledge about what shapes gut microbial communities in natural vertebrate populations. I outline a research programme that addresses this need, by developing wild small mammals as a novel system for microbiota research, and using them to address several key questions about which we currently know rather little: (1) Why do individuals within a single population show distinct gut microbial profiles, and what processes drive changes in these communities over time within individuals? (2) How exactly are gut microbes and other gut-dwelling organisms transmitted among hosts within a population - do their social interactions or shared use of space play a significant role in this process? (3) What ecological and evolutionary processes underlie variation across species in their gut microbiota?To address the first two questions, I will use a common British rodent - the wood mouse - as a model study system. Wood mice are ideal for this purpose: in the wild, a large number of individuals can be uniquely marked and monitored throughout their lives in a relatively small area, with repeated sampling of their gut microbiota and fine-scale characterisation of their local habitat. Also, manipulative experiments both in the wild and in captivity are possible with this species. To address the first question, I will use a combination of detailed field observations and controlled experiments to build a comprehensive picture of the processes shaping within-population variation in gut microbial communities. Observational data on key hypothesized factors including genetic relatedness, diet, habitat, gut parasites, age and reproductive status will allow me to estimate their relative contribution to microbiota variation within and among individuals. I will also use a large-scale drug treatment experiment in wild mice to directly test how the presence of another key group of gut inhabitants - parasitic helminths, affects the microbiota. Finally, I will perform a "diet shift" experiment in captive wood mice, to test how changes in natural food groups shape the gut microbiota. To address the second question, I will use a novel 'social network' based approach in the same wild wood mouse population used above, to examine how animal social contacts and space use drive the transmission of gut microbes and gut parasites. Finally, to answer the third question, I will perform a multi-species study using wild small mammals (mice, voles and shrews) that co-occur across several different habitat types in Europe. This study will test for the first time whether a host's evolutionary heritage or their current environmental conditions (habitat and diet), dominate in shaping their microbiota. This research will provide fundamental insight into the ecological and evolutionary processes affecting the mammalian gut microbiota, and thereby advance our knowledge about how and why these communities, which are so critical to host health, vary in nature. It will also fill an important gap in knowledge about how gut-dwelling organisms are transmitted among animals, with relevance to the control of infectious disease.