Genome-resolved house microbiome exhibits location-specific metabolic partitioning, and harbors hosts with clinically relevant antibiotic resistance genes

Residential indoor surfaces are recognized as diverse microbial ecosystems, while their genome-based organization and functional repertoires remain understudied. We recovered 2304 metagenome-assembled genomes (MAGs) from shotgun metagenomic sequencing of 10 houses in New Delhi, India. Genome-resolved analysis revealed a highly structured microbial community and substantial unexplored diversity, with 60% Species-level Genome Bins (SGBs) (629/1014) unclassified at the species level. Metabolism reveals a conserved metabolic core, along with spatial functional enrichment: the living area was significantly different from the bathroom and kitchen areas. The prevalent MAG species of the house microbiome, Paracoccus marcusii, Ottowia sp. 018060485, and Kocuria palustris, showed strain-level diversity with no stratification by house, but a subtle location-wise grouping. Potential pathogens, along with a wide range of antimicrobial resistance genes (ARGs), were identified across the MAGs, with 64 ARGs associated with mobile elements. Phylogenomic analysis of Escherichia coli MAGs indicated a split between commensal-like fecal lineages and pathotype-associated clusters, like Intestinal Pathogenic E. coli (InPEC). These results suggest that residential house microbiomes harbor microbial communities with both diverse metabolic capacity and clinical relevance. Together, these findings establish a reference for future indoor microbiome research and provide a foundation for antimicrobial resistance surveillance and the development of bio-informed building-infrastructures.