Zoonoses are the main source of emerging infectious diseases globally, and as highlighted by the COVID-19 pandemic, they can have extreme impacts on human and animal health, the economy, and the environment. As a result, there has been a renewed interest in the prediction, prevention, and mitigation of zoonotic emergence events globally, at both the scientific and policy levels. Traditionally, zoonotic disease emergence has been studied using a single pathogen model, whereby the evolutionary and epidemiological dynamics of a zoonotic pathogen are explored in the reservoir host and/or people to identify risk factors and drivers associated with spillover. While this approach can be useful for understanding individual emergence events, it has not led to the identification of unifying biological ‘rules’ or patterns that underly zoonotic spillover more broadly. Thus, our ability to proactively reduce or mitigate the impacts of zoonotic spillover at human-animal interfaces remains limited by this pathogen-focused approach.
Here, we argue that recent advances in metagenomic sequencing have ushered in a new era for zoonotic disease research that can only be fully realized through the integration and development of ecological theory. Using case studies from various high-risk human-animal interfaces previously associated with zoonotic spillover (e.g., wildlife farms in Viet Nam, urban environments in Borneo and Cambodia), we demonstrate the power of using metagenomic data to quantify and measure changes to virus community composition over time, space, or host species, including during ecosystem-wide perturbations such as land-use change, agricultural intensification, and climate change. We further suggest that co-opting tools and techniques from community ecology (e.g., trait-based approaches, network theory) to understanding the structure and function of the virome in different contexts will be critical if we are to maximize the promise of metagenomics, and progress towards understanding the key biological and ecological drivers of zoonotic diseases emergence.