Global wastewater microbiome reveals core bacterial community and viral diversity with regional antibiotic resistance patterns.

Municipal wastewater treatment plants (WWTPs) serve as global repositories for diverse and dynamic microbial communities, reflecting the complex interplay of human activities, environmental conditions, and public health challenges. Despite their importance, a comprehensive understanding of the global distribution, composition, and functional roles of these microbial ecosystems has remained elusive. Here, we present a comprehensive analysis of bacterial and viral diversities in global wastewater systems by examining 575 sampling sites across 74 cities in 60 countries. Through metagenomic analysis, we reconstructed 12,758 non-redundant bacterial metagenome-assembled genomes (MAGs) spanning 70 phyla, with 4,499 MAGs representing novel species. Despite considerable regional variation, we identified a consistent core microbiome present across 70% of global samples predominantly comprising Proteobacteria. We further assembled 1.7 million viral genomes, revealing unprecedented viral diversity with over 1.5 million species-level viral operational taxonomic units (vOTUs). Network analysis demonstrated that transport proteins play crucial roles in maintaining WWTP functional resilience against disturbances. Machine learning approaches effectively predicted continental origins of wastewater samples based on microbial signatures, confirming that microbial communities reflect local environmental and socioeconomic conditions while maintaining functional conservation. We observed significant variation in the antibiotic resistance gene (ARG) distribution, with elevated prevalence in certain African and Asian regions compared to Europe and North America. Our results establish wastewater microbiomes as important indicators of human activity and provide critical insights for advancing environmental monitoring, antimicrobial resistance surveillance, and wastewater-based epidemiology.IMPORTANCEIntensifying urbanization and human activities have dramatically increased global wastewater generation, creating complex microbial ecosystems that significantly impact environmental and public health. This study presents the first large-scale, comprehensive characterization of bacterial and viral communities in wastewater treatment systems worldwide. By analyzing samples from diverse geographical, climatic, and socioeconomic contexts, we reveal how wastewater microbiomes serve as microbial fingerprints of human society, reflecting regional characteristics while maintaining functional conservation. Our findings demonstrate that these communities function as ecological extensions of human gut microbiota in the external environment, with important implications for the spread of antibiotic resistance and pathogens. The identification of viruses as key metabolic regulators in these systems provides new perspectives on microbial community dynamics. This global-scale analysis advances our understanding of wastewater microbiology and offers valuable insights for improving wastewater management, enhancing environmental monitoring systems, and strengthening public health surveillance through wastewater-based epidemiology.