The wild mammalian microbiome
Lead Research Organisation:
Imperial College London
Department Name: Life Sciences
Abstract
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.
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.
Planned Impact
I identify four major groups that will benefit from this work.
(1) The academic community
As detailed in 'Academic Beneficiaries' this research will be of key interest to academic researchers from a range of disciplines, including microbial ecologists, infectious disease biologists and mammal ecologists. I will ensure my research achieves impact in these academic fields by publishing primary research in high impact journals (open access whenever possible), writing opinion pieces and commentaries, presenting my work at relevant conferences, and organising a workshop. The latter will facilitate the exchange of ideas and approaches between microbiota researchers working on both model and non-model organisms and forge new research directions capitalising on the strengths of different systems.
(2) Postgraduate and undergraduate students
I anticipate a significant student interest in my research. The wood mouse project I would use in objectives 1 and 2 has already proved popular among Imperial MSc and MRes students for research projects. Aurelio Malo has supervised 15 Master's projects on this system since setting it up, and I anticipate similar popularity going forward. I will engage postgraduate and undergraduate students to carry out their own research projects. Through their involvement, these students will benefit from training in microbial and disease ecology, field techniques and statistical analyses, as well as transferable skills in project and data management.
(3) The general public
Gut microbes and parasites/pathogens pervade everyone's lives, with vast numbers colonizing all animals including humans. With continual revelations about the complexity of these communities and their diverse effects on host biology, our symbiotic communities certainly capture the public's interest. Other aspects of this work are also likely to stimulate public interest, including insight into the social lives of familiar wild species, and how social interactions affect pathogen spread (currently a hot topic, for example with recent media spotlight on bovine TB). Through actively pursuing media coverage of published work, having an accessible website and blog, as well as outreach activities at public science events, I will maximise the impact my research has on public understanding and enjoyment of science.
(4) Disease control community
This work is relevant to and has potential to inform public health programmes. Millions of pounds are spent each year on deworming as part of disease control programmes in humans and livestock. The Neglected Tropical Disease (NTD) community has set ambitious goals (e.g. the London Declaration on NTDs) to control or eliminate helminths from human populations, largely through mass treatment programmes. Current strategies essentially ignore within-host community ecology: there is little consideration of how deworming may alter these communities, and the potential implications for successful disease control. Part of this proposal addresses exactly this question using wild mice as a model system, and the results will provide a test case on this key issue. I will ensure my research broadens awareness in this area by (i) communicating results at conferences attended by end-users in disease control, (ii) organising a symposium focusing on these issues at one such conference, and (iii) writing commentaries that highlight key questions and findings in this area, with collaborators in the human NTD world established through my current position.
(1) The academic community
As detailed in 'Academic Beneficiaries' this research will be of key interest to academic researchers from a range of disciplines, including microbial ecologists, infectious disease biologists and mammal ecologists. I will ensure my research achieves impact in these academic fields by publishing primary research in high impact journals (open access whenever possible), writing opinion pieces and commentaries, presenting my work at relevant conferences, and organising a workshop. The latter will facilitate the exchange of ideas and approaches between microbiota researchers working on both model and non-model organisms and forge new research directions capitalising on the strengths of different systems.
(2) Postgraduate and undergraduate students
I anticipate a significant student interest in my research. The wood mouse project I would use in objectives 1 and 2 has already proved popular among Imperial MSc and MRes students for research projects. Aurelio Malo has supervised 15 Master's projects on this system since setting it up, and I anticipate similar popularity going forward. I will engage postgraduate and undergraduate students to carry out their own research projects. Through their involvement, these students will benefit from training in microbial and disease ecology, field techniques and statistical analyses, as well as transferable skills in project and data management.
(3) The general public
Gut microbes and parasites/pathogens pervade everyone's lives, with vast numbers colonizing all animals including humans. With continual revelations about the complexity of these communities and their diverse effects on host biology, our symbiotic communities certainly capture the public's interest. Other aspects of this work are also likely to stimulate public interest, including insight into the social lives of familiar wild species, and how social interactions affect pathogen spread (currently a hot topic, for example with recent media spotlight on bovine TB). Through actively pursuing media coverage of published work, having an accessible website and blog, as well as outreach activities at public science events, I will maximise the impact my research has on public understanding and enjoyment of science.
(4) Disease control community
This work is relevant to and has potential to inform public health programmes. Millions of pounds are spent each year on deworming as part of disease control programmes in humans and livestock. The Neglected Tropical Disease (NTD) community has set ambitious goals (e.g. the London Declaration on NTDs) to control or eliminate helminths from human populations, largely through mass treatment programmes. Current strategies essentially ignore within-host community ecology: there is little consideration of how deworming may alter these communities, and the potential implications for successful disease control. Part of this proposal addresses exactly this question using wild mice as a model system, and the results will provide a test case on this key issue. I will ensure my research broadens awareness in this area by (i) communicating results at conferences attended by end-users in disease control, (ii) organising a symposium focusing on these issues at one such conference, and (iii) writing commentaries that highlight key questions and findings in this area, with collaborators in the human NTD world established through my current position.
Organisations
- Imperial College London (Lead Research Organisation)
- UNIVERSITY OF OXFORD (Collaboration)
- UNIVERSITY OF EDINBURGH (Collaboration)
- Princeton University (Collaboration)
- University of Manchester (Collaboration)
- UNIVERSITY OF NOTTINGHAM (Collaboration)
- Royal Veterinary College (RVC) (Collaboration)
- University of Queensland (Collaboration)
- University of East Anglia (Collaboration)
- University of Alberta (Collaboration)
- University of Oxford (Fellow)
People |
ORCID iD |
Sarah Knowles (Principal Investigator / Fellow) |
Publications
Kujawska M
(2022)
Bifidobacterium castoris strains isolated from wild mice show evidence of frequent host switching and diverse carbohydrate metabolism potential
in ISME Communications
Bowerman K
(2021)
Effects of laboratory domestication on the rodent gut microbiome
in ISME Communications
Brouard M
(2020)
Factors affecting woodland rodent growth
in Journal of Zoology
Hanski E
(2023)
Gut microbiota of the critically endangered Saiga antelope across two wild populations in a year without mass mortality.
in Scientific reports
Vargas-Pellicer P
(2019)
How should we store avian faecal samples for microbiota analyses? Comparing efficacy and cost-effectiveness
in Journal of Microbiological Methods
Davidson GL
(2020)
Identifying Microbiome-Mediated Behaviour in Wild Vertebrates.
in Trends in ecology & evolution
Maurice CF
(2015)
Marked seasonal variation in the wild mouse gut microbiota.
in The ISME journal
Wanelik KM
(2023)
Maternal transmission gives way to social transmission during gut microbiota assembly in wild mice.
in Animal microbiome
Webster J
(2016)
One health - an ecological and evolutionary framework for tackling Neglected Zoonotic Diseases
in Evolutionary Applications
Leung JM
(2018)
Parasite-Microbiota Interactions With the Vertebrate Gut: Synthesis Through an Ecological Lens.
in Frontiers in microbiology
Raghwani J
(2023)
Seasonal dynamics of the wild rodent faecal virome.
in Molecular ecology
Raulo A
(2021)
Social networks strongly predict the gut microbiota of wild mice.
in The ISME journal
Knowles SCL
(2019)
Species identity dominates over environment in shaping the microbiota of small mammals.
in Ecology letters
Marsh KJ
(2022)
Synchronous Seasonality in the Gut Microbiota of Wild Mouse Populations.
in Frontiers in microbiology
Lin XB
(2018)
The evolution of ecological facilitation within mixed-species biofilms in the mouse gastrointestinal tract.
in The ISME journal
Knowles S
(2023)
The genome sequence of the wood mouse, Apodemus sylvaticus (Linnaeus, 1758)
in Wellcome Open Research
Ortu G
(2016)
The impact of an 8-year mass drug administration programme on prevalence, intensity and co-infections of soil-transmitted helminthiases in Burundi.
in Parasites & vectors
Description | This award is split into 3 as I moved institution twice during my fellowship. The key findings are reported in the third and final one (based at Oxford). |
Exploitation Route | n/a see above - reported elsewhere |
Sectors | Agriculture, Food and Drink,Environment,Other |
Description | BES Large Grant |
Amount | £20,000 (GBP) |
Funding ID | 5304 / 6346 |
Organisation | British Ecological Society |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 03/2015 |
End | 01/2018 |
Description | NBAF pilot scheme |
Amount | £13,836 (GBP) |
Funding ID | NBAF969 |
Organisation | Natural Environment Research Council |
Department | NERC Biomolecular Analysis Facility (NBAF) |
Sector | Public |
Country | United Kingdom |
Start | 06/2016 |
End | 07/2017 |
Description | NC3Rs Project Grant |
Amount | £284,634 (GBP) |
Funding ID | NC/R001103/1 |
Organisation | National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) |
Sector | Public |
Country | United Kingdom |
Start | 09/2017 |
End | 04/2019 |
Description | NERC |
Amount | £42,040 (GBP) |
Funding ID | BRIS/100/05/17 |
Organisation | Natural Environment Research Council |
Sector | Public |
Country | United Kingdom |
Start | 12/2017 |
End | 07/2018 |
Description | RVC Internal PhD studentship scheme |
Amount | £63,000 (GBP) |
Organisation | Royal Veterinary College (RVC) |
Sector | Academic/University |
Country | United Kingdom |
Start | 01/2017 |
End | 01/2020 |
Title | Comparative rodent microbiota dataset |
Description | I have collected samples from a range of rodent species in Lithuania and sequenced the microbiome using 16S sequencing, for the third objective of my fellowship proposal. The dataset awaits analysis. |
Type Of Material | Database/Collection of data |
Year Produced | 2015 |
Provided To Others? | No |
Impact | F1000 recommended article in Ecology Letters, see publications; dataset in European Research Archive: PRJEB30121 |
Title | Diet shift-microbiome dataset |
Description | A complete set of data on how diet shifts influence the microbiome of wood mice in captivity |
Type Of Material | Database/Collection of data |
Year Produced | 2018 |
Provided To Others? | No |
Impact | None yet |
Title | Wild mice microbiome and social network dataset |
Description | I collected a full year of faecal samples from fortnightly trapping a wild wood mouse population at Silwood Park, along with detailed meta-data on this population, including data of high spatiotemporal resolution on individual space use that can be used to generate a social network for the population. The samples have been used to characterise gut parasite infection status, and are ready to have the microbiome sequenced for a key objective in my fellowship research. |
Type Of Material | Database/Collection of data |
Provided To Others? | No |
Impact | None yet |
Title | Wild rodent trapping, tracking and sampling for genetics and gut microbiome, Silwood Park, Berkshire, November 2014 to November 2015 |
Description | This data set is a combination of trapping data, tracking data and data on the genetic relatedness and gut microbiome composition of wild rodents caught in 2.3 ha study site in Nash's Copse, Silwood Park, from November 2014 to November 2015. As part of a longer-term capture-mark-recapture study, three species of rodents were trapped with Sherman live-traps fortnightly for 12 months: wood mouse (Apodemus sylvaticus), yellow-necked mouse (Apodemus flavicollis) and bank vole (Myodes glaerolus). Upon capture, they were measured, weighted, sexed, aged and a tissue sample and a faecal sample were collected from all mouse individuals for genetic and microbiome analyses. All rodents were released to their location of capture. First time each individual was captured, they were injected with a permanent subcutaneous identification Radio-Frequency Identification(RFID)-tag (Passive Integrated Transponde-tag). The tagged rodents were subsequently tracked with a set of custom-made tracking devices (loggers). Loggers produced dense time-stamped occurrence data suitable for inferring spatio-temporal activity patterns of rodents, such as temporal niches, home ranges and social networks. Tissue samples were used to genotype the wood mouse population and bacterial DNA extracted from faecal samples were used to profile their gut microbiome composition. This work was funded by a NERC independent Research Fellowship to Sarah Knowles (NE/L011867/1) |
Type Of Material | Database/Collection of data |
Year Produced | 2022 |
Provided To Others? | Yes |
URL | https://catalogue.ceh.ac.uk/id/c67fde7f-a1c8-4cb4-a76e-0c6d21c82222 |
Title | Wytham wild rodent ecology and microbiome dataset |
Description | We are building a long-term dataset of wild mouse ecology (longitudinal sampling every fortnight since 2015) and microbiome samples, to address questions in my NERC fellowship. The first 2 years of sampling and data are now complete. |
Type Of Material | Database/Collection of data |
Year Produced | 2017 |
Provided To Others? | No |
Impact | None yet |
Description | Collaboration with Alan Wilson - zebra microbiome |
Organisation | Royal Veterinary College (RVC) |
Department | Structure and Motion Laboratory |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | I have sequenced a pilot set of faecal samples from Plains Zebra, in order to characterise their gut microbiome. We are both developing ideas for grant applications on this new system. |
Collaborator Contribution | Alan's group conducted fieldwork to collect samples from Zebra in Botswana |
Impact | None yet. Collaboration is multi-disciplinary - involving engineers, biomathematicians/biophysicists and ecologists. |
Start Year | 2017 |
Description | Collaboration with Amy Pedersen and Adrian Smith: Helminth-microbiota interactions |
Organisation | University of Edinburgh |
Department | School of Biology |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | I am collaborating with Amy and her PhD student, as well as Adrian Smith at Oxford to characterise gut microbiome changes in response to helminth infection in the wood mouse. I am contributing financially and in terms of expertise for the microbiome sequencing. |
Collaborator Contribution | Amy's group performed the experiments, using the captive wood mouse colony she runs in Edinburgh, is carrying out the lab work, and paid for DNA extractions. Adrian's group contribute in terms of expertise, particularly in library preparations for NGS. |
Impact | None yet - samples being processed |
Start Year | 2016 |
Description | Collaboration with Amy Pedersen and Adrian Smith: Helminth-microbiota interactions |
Organisation | University of Oxford |
Department | Department of Zoology |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | I am collaborating with Amy and her PhD student, as well as Adrian Smith at Oxford to characterise gut microbiome changes in response to helminth infection in the wood mouse. I am contributing financially and in terms of expertise for the microbiome sequencing. |
Collaborator Contribution | Amy's group performed the experiments, using the captive wood mouse colony she runs in Edinburgh, is carrying out the lab work, and paid for DNA extractions. Adrian's group contribute in terms of expertise, particularly in library preparations for NGS. |
Impact | None yet - samples being processed |
Start Year | 2016 |
Description | Collaboration with Andrea Graham and Jackie Leung, Princeton |
Organisation | Princeton University |
Country | United States |
Sector | Academic/University |
PI Contribution | We have written a review article together. Myself and Jackie researched and wrote the paper, Andrea provided critical comment |
Collaborator Contribution | Jackie helped prepare and write the paper, both contributed intellectually and Andrea comments on drafts |
Impact | Review article published in Frontiers Microbiol |
Start Year | 2015 |
Description | Collaboration with Jens Walter |
Organisation | University of Alberta |
Country | Canada |
Sector | Academic/University |
PI Contribution | Jens used some samples from my comparative rodent microbiome project for his studies of Lactobacillus reuteri biology in rodents, leading to publication of a paper "The evolution of ecological facilitation within mixed-species biofilms in the mouse gastrointestinal tract" in ISME J. |
Collaborator Contribution | Jens received samples, isolated bacteria and characterised their genotype to assess Lactobacillus reuteri diversity across rodent species, and their in vivo interactions. His group drove the project and wrote the paper, which I commented on and edited. |
Impact | One paper published in ISME Journal "The evolution of ecological facilitation within mixed-species biofilms in the mouse gastrointestinal tract" |
Start Year | 2015 |
Description | Collaboration with Lindsay Hall: wild rodent Bifidobacteria |
Organisation | University of East Anglia |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Lindsay, her PhD student and I initiated a collaboration to characterise whole genomes of Bifidobacteria strains from wild rodents. We supply faecal samples from fieldwork and intellectual input. |
Collaborator Contribution | Lindsay's group perform lab work to grow the bacteria, sequence the genomes and analyse them, and fund this side of the collaboration. |
Impact | Paper just published in 2022: https://doi.org/10.1038/s43705-022-00102-x |
Start Year | 2017 |
Description | Wild rodent gut microbe genome characterisation |
Organisation | University of Manchester |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | To date, my input has been intellectual, scientific expertise and samples. I contacted Philip and Kate Bowerman to collaborate and investigate bacterial metagenomics within some of my wild rodent faecal samples. I had found an interesting result that a particular group of bacteria he works on (family S24-7) were driving host species-specificity in the comparative rodent microbiome dataset associated with this award, and so we collaborated to sequence some genomes from these samples to explore these taxa further. |
Collaborator Contribution | Kate and Philip have characterised gut bacterial genomes from a set of the samples I collected. |
Impact | ISME Communications publication in 2022: https://doi.org/10.1038/s43705-021-00053-9 |
Start Year | 2018 |
Description | Wild rodent gut microbe genome characterisation |
Organisation | University of Nottingham |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | To date, my input has been intellectual, scientific expertise and samples. I contacted Philip and Kate Bowerman to collaborate and investigate bacterial metagenomics within some of my wild rodent faecal samples. I had found an interesting result that a particular group of bacteria he works on (family S24-7) were driving host species-specificity in the comparative rodent microbiome dataset associated with this award, and so we collaborated to sequence some genomes from these samples to explore these taxa further. |
Collaborator Contribution | Kate and Philip have characterised gut bacterial genomes from a set of the samples I collected. |
Impact | ISME Communications publication in 2022: https://doi.org/10.1038/s43705-021-00053-9 |
Start Year | 2018 |
Description | Wild rodent gut microbe genome characterisation |
Organisation | University of Queensland |
Department | School of Chemistry and Molecular Biosciences |
Country | Australia |
Sector | Academic/University |
PI Contribution | To date, my input has been intellectual, scientific expertise and samples. I contacted Philip and Kate Bowerman to collaborate and investigate bacterial metagenomics within some of my wild rodent faecal samples. I had found an interesting result that a particular group of bacteria he works on (family S24-7) were driving host species-specificity in the comparative rodent microbiome dataset associated with this award, and so we collaborated to sequence some genomes from these samples to explore these taxa further. |
Collaborator Contribution | Kate and Philip have characterised gut bacterial genomes from a set of the samples I collected. |
Impact | ISME Communications publication in 2022: https://doi.org/10.1038/s43705-021-00053-9 |
Start Year | 2018 |
Description | Curiosity Carnival |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | I talked about small mammal research at the Wytham Woods Curiosity Carnival, telling members of the General Public what we do |
Year(s) Of Engagement Activity | 2017 |