The Impact of Metagenomic Surveillance of Wastewater-Driven Feedbacks on One Health Policy Effectiveness and Agricultural Sustainability: A Systematic Review

Background: Wastewater occupies a critical nexus at the confluence of human activity, environmental change, and microbial evolution. This review synthesizes the emerging role of wastewater as a mirror of community health and a driver of microbial and resistome restructuring across environmental compartments. Wastewater systems harbor diverse biological and chemical markers, including pathogens, antimicrobial resistance genes (ARGs), pharmaceuticals, and nutrients, reflecting dynamic population health, agricultural practices, and socioeconomic activities. Advanced metagenomic approaches reveal that wastewater treatment plants (WWTPs) are global hotspots for the selection and spread of resistant bacteria, mobile genetic elements, and opportunistic pathogens, even after secondary or tertiary treatment. Main Body: The reuse of treated wastewater for irrigation enhances soil fertility and crop yields, particularly in water-scarce regions, but also facilitates the introduction and persistence of ARGs and contaminants in soils, crops, and food animal microbiomes. Downstream, this microbial restructuring influences nutrient cycling, crop productivity, animal gut health, and economic resilience—ultimately affecting food safety, pharmaceutical efficacy, and international trade dynamics. The multilevel interactions highlighted in this review support a One Health framework, integrating human, animal, and environmental perspectives for comprehensive risk assessment and management. Wastewater-based surveillance now emerges as a valuable, cost-effective tool for early warning of antimicrobial resistance trends and for informing policy interventions beyond conventional clinical monitoring. However, balancing the resource benefits of wastewater reuse with the risks posed by microbial contaminants and resistance determinants remains a major challenge. Conclusion: This review advocates multi-faceted actions: optimizing WWTP operations and effluent quality; guiding agricultural and livestock practices using reclaimed-water profiles; implementing robust microbiome and resistome surveillance; and harmonizing policy frameworks at local and global scales. Collaborative efforts are needed to transform wastewater from a source of risk into a strategic resource for resilient agriculture, sustainable water management, and global public health in the face of escalating water scarcity and antimicrobial resistance. Bringing together mechanistic microbiome insights, quantitative risk modeling, and translational policy guidance, this synthesis highlights wastewater’s pivotal role in shaping environmental microbiomes and resilience within rapidly changing socioecological systems.