Soil Microbiome Signatures Associated with Epidemiological Heterogeneity Across Natural Plague Foci in Inner Mongolia, China

Plague persistence relies on complex host–vector–environment interactions, yet the ecological contribution of soil microbiomes to natural foci remains poorly understood. We performed shotgun metagenomic sequencing of 143 soil samples across four distinct plague foci in Inner Mongolia, China, to characterize microbiome features associated with contrasting epidemiological states. Taxonomic, functional, and network analyses showed that the three active plague foci exhibited lower microbial diversity, simplified co-occurrence networks, and enrichment of specific taxa, particularly Streptomyces. Conversely, the quiescent Marmota sibirica focus harbored a more complex and interconnected microbial network with greater richness and exclusive detection of Yersinia bacteriophages, showing significant concordance with bacterial community structure. These patterns indicate distinct microbiome configurations associated with specific host and geographic settings, highlighting the need to disentangle host- and site-specific effects from broader epidemiological status. Compared with surface and deep soil, burrow-associated soil exhibited greater microbial differentiation and higher richness of bacteriophages, antimicrobial resistance genes, and virulence-associated genes, suggesting its potential as a sensitive environmental matrix for ecological monitoring. Overall, our findings identify distinct soil microbiome signatures—specifically taxonomic shifts, altered network complexity, exclusive Yersinia phage detection, and functional gene enrichment—associated with epidemiological heterogeneity across natural plague foci, providing a baseline for understanding ecological variation among endemic habitats.