The wild mammalian microbiome

野生哺乳动物微生物组

• 批准号: NE/L011867/1
• 负责人: Sarah Knowles
• 金额: $ 70.78万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=NE%2FL011867%2F1
• 关键词: wild; mammalian; microbiome

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.

脊椎动物的肠道中充满了巨大的、多样化的细菌群落，它们的数量至少比寄主细胞的数量多一个数量级，即所谓的肠道微生物区系。分子生物学的最新进展使对这些细菌群落的研究发生了革命性的变化，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，它们的巨大变异性也暴露了出来--随着时间的推移，它们在不同物种、不同个体之间以及个体内部都存在巨大差异。这种变异需要一个解释，然而我们目前对生态和进化过程的了解仍然有限。这方面的一个关键障碍是，到目前为止，微生物区系研究主要集中在两种模式生物上--人类和实验室小鼠，这使得人们对自然脊椎动物种群中肠道微生物群落的形成缺乏了解。我概述了一个解决这一需求的研究计划，通过开发野生小型哺乳动物作为微生物区系研究的新系统，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谱，随着时间的推移，是什么过程推动了这些群落在个体内部的变化？(2)肠道微生物和其他肠道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享空间的使用在这个过程中发挥了重要作用吗？(3)在它们肠道微生物区系中，哪些生态和进化过程是不同物种之间差异的基础？为了回答前两个问题，我将使用一种常见的英国啮齿动物--林鼠--作为一个模型研究系统。木鼠是实现这一目的的理想之选：在野外，可以在相对较小的区域内对大量个体进行独特的标记和一生的监测，对它们的肠道微生物区系进行重复采样，并对它们的当地栖息地进行精细的表征。此外，无论是在野外还是在圈养中，这种物种都有可能进行操控实验。为了回答第一个问题，我将结合详细的实地观察和对照实验来构建一幅塑造肠道微生物群落种群内变异的过程的综合图景。关于关键假设因素的观测数据，包括遗传相关性、饮食、栖息地、肠道寄生虫、年龄和生殖状况，将使我能够估计它们对个体内和个体之间微生物区系变化的相对贡献。我还将在野鼠身上进行一项大规模的药物治疗实验，直接测试另一组关键肠道居民--寄生蠕虫--的存在对微生物区系的影响。最后，我将在圈养的木质小鼠身上进行一项“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区系。为了回答第二个问题，我将在上面使用的同一野生林鼠种群中使用一种新的基于社交网络的方法，来研究动物的社交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，我将使用欧洲几种不同栖息地共存的野生小型哺乳动物(老鼠、田鼠和地鼠)进行一项多物种研究。这项研究将首次测试宿主的进化遗产或他们目前的环境条件(栖息地和饮食)是否主导了他们的微生物区系。这项研究将为影响哺乳动物肠道微生物区系的生态和进化过程提供基本的见解，从而促进我们对这些对宿主健康如此关键的群落在自然界中如何以及为什么发生变化的了解。它还将填补有关肠道微生物如何在动物之间传播的知识的一个重要空白，这与传染病的控制有关。

项目成果

The genome sequence of the wood mouse, Apodemus sylvaticus (Linnaeus, 1758)

木鼠Apodemus sylvaticus 的基因组序列（Linnaeus，1758）

• DOI: 10.12688/wellcomeopenres.20001.1
• 发表时间: 2023
• 期刊: Wellcome Open Research
• 作者: Knowles S

Gut microbiota of the critically endangered Saiga antelope across two wild populations in a year without mass mortality.

• DOI: 10.1038/s41598-023-44393-z
• 发表时间: 2023-10-11
• 期刊: SCIENTIFIC REPORTS
• 影响因子: 4.6
• 作者: Hanski, Eveliina;Khanyari, Munib;Li, Jingdi;Bates, Kieran A.;Zuther, Steffen;Maiden, Martin C. J.;Kock, Richard;Knowles, Sarah C. L.
• 通讯作者: Knowles, Sarah C. L.

Factors affecting woodland rodent growth

影响林地啮齿动物生长的因素

• DOI: 10.1111/jzo.12822
• 发表时间: 2020
• 期刊: Journal of Zoology
• 影响因子: 2
• 作者: Brouard M

The impact of albendazole treatment on the incidence of viral- and bacterial-induced diarrhea in school children in southern Vietnam: study protocol for a randomized controlled trial.

• DOI: 10.1186/s13063-016-1406-1
• 发表时间: 2016-06-06
• 期刊: Trials
• 影响因子: 2.5
• 作者: Leung JM;Hong CT;Trung NH;Thi HN;Minh CN;Thi TV;Hong DT;Man DN;Knowles SC;Wolbers M;Hoang Nle T;Thwaites G;Graham AL;Baker S
• 通讯作者: Baker S

Parasite-Microbiota Interactions With the Vertebrate Gut: Synthesis Through an Ecological Lens.

• DOI: 10.3389/fmicb.2018.00843
• 发表时间: 2018
• 期刊: Frontiers in microbiology
• 影响因子: 5.2
• 作者: Leung JM;Graham AL;Knowles SCL
• 通讯作者: Knowles SCL