Unveiling Global Diversity of Patescibacteriota and Functional Interactions with Host Microbes

Abstract Patescibacteriota, also known as Candidate Phyla Radiation (CPR), is a diverse clade of ultra‐small bacteria with an epibiotic lifestyle. Despite their ubiquity across diverse ecosystems and ecological importance in microbial networks, the global distribution of Patescibacteriota and functional interactions with their host organisms remain largely unknown. Here, by leveraging comprehensive Patescibacteriota genomic resources and global multi‐habitat metagenomic datasets, it is demonstrated that ribosomal protein S3 (rpS3) as a reliable phylogenetic marker, enabling accurate recovery of Patescibacteriota diversity from short‐read metagenomes. Using this framework, extensive taxonomic diversity and pronounced community heterogeneity are uncovered across eight ecosystems. Through network analysis and genome‐wide functional screening, habitat‐specific co‐occurrence patterns are also revealed between Patescibacteriota and host‐associated bacteria, especially potential functional synergies mediated by metabolic pathway cascades. Notably, Patescibacteriota‐encoded NirK may assist sulfate‐reducing bacteria in resisting nitrite stress, while NorB can mitigate nitric oxide toxicity for complete ammonia‐oxidizing bacteria. Taken together, this study highlights the underappreciated diversity of Patescibacteriota and elucidates its important role in supporting host metabolism through complementary biochemical functions, offering new insights into its ecological significance and evolutionary adaptations in the global ecosystem.