Absolute quantitative metagenomic profiling reveals divergent antimicrobial resistance and pathogen hazards in urban and rural aging community wastewater

Bacterial infections pose a significant threat to vulnerable populations, particularly where traditional clinical surveillance is inadequate. Here, we conducted a six-month wastewater-based surveillance (WBS) in urban and rural communities of Xi’an, China, integrating absolute quantitative metagenomic sequencing (AQMS) and whole-genome sequencing (WGS). Our AQMS profiling revealed distinct spatio-temporal dynamics across four major pathogen categories: human respiratory, livestock-related, waterborne, and poultry-related pathogens. Crucially, cross-validation with local epidemiological records demonstrated that quantitative surges in wastewater pathogen loads (e.g., Streptococcus pneumoniae , Vibrio parahaemolyticus ) closely tracked, and in some instances preceded, the peaks of clinical pneumonia and acute diarrhea outpatient visits. Furthermore, WGS of environmental and clinical isolates illuminated a stark epidemiological dichotomy. Urban wastewater was characterized by a diverse array of human-adapted, multidrug-resistant (MDR) high-risk clones, including Escherichia coli ST182 and Klebsiella pneumoniae ST6853 (a variant of the epidemic ST11), which clustered phylogenetically with local clinical strains. Conversely, rural wastewater was predominantly shaped by agricultural runoff and patterns consistent with zoonotic spillover, evidenced by the emergence of livestock-associated lineages such as E. coli ST316, K. pneumoniae ST37, Salmonella ST10, a cattle-derived Bacillus paranthracis , and Streptococcus suis ST7. By establishing a robust etiological link between environmental signals and actual human infections, this study demonstrates that community-level WBS serves as an accurate, real-time mirror of the circulating clinical resistome. Ultimately, this integrated framework provides actionable decision support for implementing environment-specific interventions, ranging from dynamic adjustments in urban wastewater treatment to targeted on-farm biosecurity protocols in rural areas.