Coexistence of Virome-Encoded Human Probiotic Genes and Pathogenic Genes in Global Habitats

Some probiotic genes for humans obtained through horizontal gene transfer (HGT) have been screened in viral genomes, yet the occurrence mode, geographic distribution, and functional characteristics of these genes in viruses and the coexistence between pathogenic virulence genes and probiotic genes in the viral genome, remain insufficiently understood and verified. In this study, using IMG/VR v4 database, 4,556 viruses carrying probiotic gene segments have been discovered in eight habitat types (humans, animals, freshwater, marine, other water bodies, soil, and plants), 13 regions of 76 countries around the world. Among them, the 478 viruses carrying probiotic genes that distributed in humans account for the highest proportion among the viruses with predictable hosts. In viruses carrying probiotic genes, BCO1, bioB, COQ2, GPX1, GSTs, GSTT1, GULO, and menA are not only probiotic genes encoded by viruses, but also auxiliary metabolic genes. Four virulence genes harmful to humans in viral sequences carrying probiotic genes with transcription and expression potential, have been found, indicating that virulence genes encoded by viruses can coexist with probiotic genes. Further metagenome sequencing revealed the consistency between the probiotic gene asd in the bacillus prophage and the corresponding phage auxiliary metabolic genes. This study integrates probiotic gene databases into viral genomics, revealing the compatibility between viral probiotic and virulence genes, and offering new insights for viral applications. IMPORTANCEProbiotic genes acquired by humans through horizontal gene transfer (HGT) have been identified within viral genomes. However, their occurrence, distribution, and functions, along with the coexistence of pathogenic and probiotic genes in viruses, remain poorly understood. This study advocates for the utilization of probiotic gene databases in viral genomes and innovatively elucidates the phenomenon of compatibility between viral probiotic genes and virulence genes, offering fresh perspectives on the diverse applications of viruses. By promoting the application of these databases, the study reveals the compatibility between probiotic and pathogenic genes in viruses, providing novel and insightful implications for the various utilizations of viruses.