Sustained fecal-oral human-to-human transmission following a zoonotic event

•Pathogens that transmit via the fecal-oral route are generally very stable.•Different pathogens have similar requirements to become human-to-human transmissible.•Research strategies for zoonotic pathogens should include mechanisms of transmission. Bacterial, viral and parasitic zoonotic pathogens that transmit via the fecal-oral route have a major impact on global health. However, the mechanisms underlying the emergence of such pathogens from the animal reservoir and their persistence in the human population are poorly understood. Here, we present a framework of human-to-human transmission of zoonotic pathogens that considers the factors relevant for fecal-oral human-to-human transmission route at the levels of host, pathogen, and environment. We discuss current data gaps and propose future research directions.