Giant extrachromosomal element "Inocle" potentially expands the adaptive capacity of the human oral microbiome.

Survival strategy of bacteria is expanded by extrachromosomal elements (ECEs). However, their genetic diversity and functional roles for adaptability are largely unknown. Here, we discover a novel family of intracellular ECEs using 56 saliva samples by developing an efficient microbial DNA extraction method coupled with long-read metagenomics assembly. Even though this ECE family was not hitherto identified, our global prevalence analysis using 476 salivary metagenomic datasets elucidates that these ECEs reside in 74% of the population. These ECEs, which we named, "Inocles", are giant plasmid-like circular genomic elements of 395 kb in length, including Streptococcus as a host bacterium. Inocles encode a series of genes that contribute to intracellular stress tolerance, such as oxidative stress and DNA damage, and cell wall biosynthesis and modification involved in the interactions with oral epithelial cells. Moreover, Inocles exhibit significant positive correlations with immune cells and proteins responding to microbial infection in peripheral blood. Intriguingly, we examine and find their marked reductions among 68 patients of head and neck cancers and colorectal cancers, suggesting its potential usage for a novel biomarker of gastrointestinal cancers. Our results suggest that Inocles potentially boost the adaptive capacity of host bacteria against various stressors in the oral environment.