Wastewater Proteomics for One Health Surveillance: Progress, Challenges, and Opportunities

Wastewater-based surveillance enables population-level monitoring of chemical exposures, pathogens, and antimicrobial resistance. Proteomics could extend this framework by providing direct information on biological function through proteins derived from human excreta and microbial communities. Although only a few untargeted wastewater proteomics studies have been reported, they show that characterizing the wastewater proteome is technically feasible and that clinically relevant human proteins are consistently detected despite the complexity of the matrix. In this review, we examine the current state of wastewater proteomics and evaluate its potential for One Health surveillance. We summarize insights on the composition of the wastewater proteome and discuss methodological considerations spanning sampling, protein recovery, mass spectrometry, and bioinformatics, drawing on established practices from wastewater-based surveillance, clinical proteomics, and environmental metaproteomics. We then discuss applications, including biomarker discovery for human disease surveillance, microbial community function and antimicrobial resistance, and outline key challenges and future directions. The available evidence, though still limited, indicates that wastewater proteomics is moving from proof of concept toward methodological optimization and biological validation. Future progress will depend on standardized analytical workflows, longitudinal validation studies, dedicated wastewater protein reference databases, and governance frameworks that develop in parallel with technical advances.