Fecal virome at the human-animal interface: a one health perspective on an uncharted frontier

The exponential growth of the human population and associated intensifications in animal farming, pet ownership, and habitat anthropisation have dramatically increased human-animal interactions. Global livestock production now exceeds 24 billion animals annually, and pet ownership has risen to over 70% of households in many developed nations, creating unprecedented interfaces for viral exchange. This heightened contact has multiplied opportunities for zoonotic and reverse-zoonotic transmission, as tragically exemplified by the SARS-CoV-2 pandemic. The fecal virome—defined as the totality of viral nucleic acids in the gastrointestinal tract—represents a crucial, yet largely unexplored, pathway for such exchanges. While the bacterial microbiome’s role is increasingly recognized, the virome’s composition, dynamics, and transmissibility between co-habiting humans and animals remain poorly characterized. This review compiles current evidence on the fecal virome of key domestic animals (equines, livestock, pets) and their human contacts under the “One Health” framework. We critically evaluate methodological approaches—from targeted PCR to viral metagenomics—and highlight the discovery of novel viruses and identification of zoonotic agents through metagenomic approaches. Critically, we identify significant knowledge gaps, including the absence of definitive evidence for contemporary cross-species transmission versus shared ancestry or convergent evolution. We propose a strategic research agenda focused on longitudinal studies of human-animal cohorts, standardized metagenomic methodologies, and functional analyses of the virome. Elucidating the fecal virome at this interface is paramount for developing proactive surveillance strategies to predict and prevent the next emerging viral disease.