[22-EEID] Ecology and evolution of pathogen-microbiome-host interactions during population-level intermingling
Lead Research Organisation:
University of Liverpool
Department Name: Livestock and One Health
Abstract
Commingling events occur when unfamiliar animals or people come together in a defined space and time with intensive and sustained contact. Commingling is associated with increased infectious pathogen transmission risk with possible global consequences, as the COVID-19 pandemic has highlighted. Commingling events in humans include mass-gathering events, back-to-school, air travel, incarceration, and mass migration. In livestock production, commingling routinely occurs in beef finishing systems and may occur on a national level when farmers rebuild herds following depopulation events, such as the recent foot-and-mouth disease outbreaks in the U.K. Commingling induces multi-level ecosystem disruption including perturbed social structure, co-circulating viral variants, host immune and physiological dyscrasia, and unstable microbial dynamics. We hypothesize that these interrelated processes create opportunity for viral transmission via three distinct mechanisms: 1) exposure of hosts to previously unseen viral variants; 2) host physiologic stress, including increased inflammation and immune system perturbation; and 3) ecological and evolutionary shifts in the microbiome. To test these hypotheses, we will perform controlled commingling trials using cattle relative to bovine coronavirus (BCV) transmission as a model system and pathogen, respectively. Using unique calf populations and facilities in the US and UK, we will generate highly-resolved time series datasets for BCV variant behaviour, host immune-inflammatory responses, and microbiome dynamics during commingling. Microbiome and BCV data will be analysed at the nucleotide level to uncover temporal variant- and strain-level ecology and evolution during commingling. We will model host immune-inflammatory responses as a multi-component system using specific markers and transcriptome analysis. We will then use these data to populate two novel temporal models of virus behaviour: first, an epidemiological risk factor model for disease during commingling using dynamic Bayesian network analysis; and second, a spatiotemporal SEIR pathogen transmission model that incorporates parameters for host immune response and microbiome eco-evolutionary shifts during commingling events.
Intellectual Merit
The world is experiencing an inexorable trend towards increasingly frequent, intensive, large-scale commingling events among humans and animals. This has ramifications for viral transmission and variant evolution. There is an urgent need to understand the theoretical basis of virus dynamics specifically during these commingling events. A largely unexplored component of viral transmission during commingling is the host microbiome, which experiences dramatic shifts during commingling events. Our work has intellectual merit because it explicitly models these microbiome dynamics within a transmission and risk factor modelling framework. This will allow us to uncover organizing principles of viral transmission during commingling, which will advance theoretical understanding of virus behaviour at the variant level. Our work also improves and extends existing infectious disease modelling approaches by incorporating critical commingling and microbiome dynamics with temporal and host stochasticity. Finally, we would provide the scientific community with a highly-resolved empirical dataset as well as a novel study platform for future research on infectious disease dynamics during commingling events.
Broader Impacts
We propose to develop an integrated program that will train veterinary students in research experiences and advanced epidemiological methods that will help build the next generation of agricultural leaders and researchers. We also propose a series of Bioinformatics Workshops to engage agricultural researchers in primary analysis of genomic data. Our project outcomes will have immediate relevance to livestock husbandry practices.
Intellectual Merit
The world is experiencing an inexorable trend towards increasingly frequent, intensive, large-scale commingling events among humans and animals. This has ramifications for viral transmission and variant evolution. There is an urgent need to understand the theoretical basis of virus dynamics specifically during these commingling events. A largely unexplored component of viral transmission during commingling is the host microbiome, which experiences dramatic shifts during commingling events. Our work has intellectual merit because it explicitly models these microbiome dynamics within a transmission and risk factor modelling framework. This will allow us to uncover organizing principles of viral transmission during commingling, which will advance theoretical understanding of virus behaviour at the variant level. Our work also improves and extends existing infectious disease modelling approaches by incorporating critical commingling and microbiome dynamics with temporal and host stochasticity. Finally, we would provide the scientific community with a highly-resolved empirical dataset as well as a novel study platform for future research on infectious disease dynamics during commingling events.
Broader Impacts
We propose to develop an integrated program that will train veterinary students in research experiences and advanced epidemiological methods that will help build the next generation of agricultural leaders and researchers. We also propose a series of Bioinformatics Workshops to engage agricultural researchers in primary analysis of genomic data. Our project outcomes will have immediate relevance to livestock husbandry practices.
Technical Summary
The overall goal of this proposal is to understand the multi-level ecological processes that drive pathogen transmission during periods of intensive mixing of conspecifics with little contact history (i.e., "commingling"). Commingling events (e.g., the start of school, migration, air travel, or re-grouping of livestock animals) are long known to be associated with increased disease risk, much of which has been attributed to increased duration and frequency of host contact. Increasing evidence suggests, however, that these commingling events contain a hidden dimension - namely, the intensive mixing of heterogeneous holobionts, i.e., hosts and their associated microbiomes, which together represent a cohesive unit. Importantly, these host-associated microbiomes can contain potential pathogens, which under the appropriate conditions break out of their microbial milieu to translocate, replicate, transmit and invade. Indirect evidence suggests that commingling events create ideal conditions for this type of pathogen behaviour, and that instability within the holobiont is a major component of these "ideal" conditions. However, there is little direct observational data to support an appropriate model for how these different ecological dynamics impact pathogen transmission - specifically, interrelated dynamics at the population, host and microbiome levels. We hypothesize that commingling intensity drives host population structure and microbiome instability, which in turn modulate pathogen dynamics. To test this overarching hypothesis, we leverage calves on commercial farms (US) and controlled experimental facility (UK) as an optimal study system to generate highly-resolved data at the level of populations, hosts, and microbes. We use bovine coronavirus as an important respiratory and gastrointestinal pathogen that demonstrates similar epidemiological, immunological and genetics to SARS-CoV-2, a virus of immediate global importance.
People |
ORCID iD |
Joseph Neary (Principal Investigator) | |
Peers Davies (Co-Investigator) |
Description | University announcement of research award and collaboration |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | Announcement of the research award and collaboration with US institutions. |
Year(s) Of Engagement Activity | 2023 |
URL | https://news.liverpool.ac.uk/2023/11/03/uk-us-collaboration-to-study-viral-transmission-during-mass-... |