Abstract

Rodents and shrews are important reservoir hosts due to their close association with human activities and their role in carrying various zoonotic pathogens. Recently, meta-transcriptomic sequencing has become a powerful tool for surveilling and screening novel pathogens from wild animals. However, many of these studies focused only on the diversity and genetic evolution of viruses from wildlife, while ignoring non-viral pathogens such as bacterial and eukaryotic microorganisms. Here, we performed a comprehensive infectome analysis of 227 tissue samples collected from 42 rodents and 16 shrews across six cities of Guangdong Province, China. We identified 34 viral families, including 23 mammalian viruses. Phylogenetic analysis revealed a henipavirus from the kidneys of shrews closely related to the Langya virus with potential infection risks to humans. Additionally, two potential pathogenic bacteria and 12 eukaryotic pathogens from six genera were found, showing clearer organ tropism than viruses. Interestingly, a moderate positive abundance correlation between Usmuvirus newyorkense and Trichinella suggested a potential virus–parasite association. We used machine learning models to evaluate the zoonotic potential of the obtained viruses, which indicated that 15 of 23 viral species were high risk for human infection. These findings provide important insight into the substantial zoonotic threat posed by pathogens circulating in wild small mammals in southern China and highlight the necessity for persistent wildlife pathogen surveillance.