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unusually large DNA rings in the oral microbiome
Researchers have identified exceptionally large loops of DNA carried by bacteria in the human mouth that may influence oral health and immune interactions, and could be linked to lower rates of some cancers. The circular genetic elements, coined "Inocles," appear to be a new class of very large plasmid-like extrachromosomal DNA found in Streptococcus species that colonize the oral cavity.
University of Tokyo investigators led the study that first described Inocles. According to the team, these rings act like modular gene packages that help bacteria adapt to the stressful and fluctuating environment of the mouth — effectively extra survival tools beyond the bacteria’s main chromosome. As the lead microbiologist on the project explains, exploring the oral microbiome reveals many genetic mechanisms that remain poorly understood; Inocles add a previously unseen layer to that complexity.
Inocles were found in Streptococcus bacteria. (Kiguchi et al., Nat. Commun., 2025)
How the elements were found and how common they are
The discovery started with a focused sequencing analysis of saliva from 56 volunteers. To test how widespread the structures are, the team then screened an extended set of 476 saliva samples. The results indicate that roughly three-quarters of people sampled carry Inocles in their oral bacteria, suggesting these elements are common components of the oral microbiome.
One challenge that delayed recognition of Inocles is their large size. Standard short-read sequencing workflows fragment DNA into small pieces before assembly, making very large circular elements hard to reconstruct. To address this, the researchers developed a tailored pipeline called preNuc that removes human DNA from saliva samples before sequencing, dramatically simplifying assembly of bacterial genomes and large extrachromosomal elements. Using this approach, they measured an average Inocle length of about 350 kilobase pairs — an order of magnitude larger than many typical plasmids, which are usually tens of kilobase pairs.
Genes, functions and possible protective effects
Functional content
The expanded length of Inocles carries genes that plausibly contribute to bacterial survival in the mouth: systems for resisting oxidative stress, pathways involved in DNA damage repair, and cell wall–related genes that could tune responses to extracellular stress. These functions suggest Inocles might help Streptococcus strains persist under immune attack, frequent pH shifts, and exposure to reactive molecules in the oral cavity.
Association with cancer
In an unexpected pattern, saliva samples from people with head and neck cancers contained substantially fewer Inocles than samples from cancer-free individuals. This correlation hints at a potential protective role for the elements — either directly affecting local tumor risk or indirectly reflecting broader changes in oral ecology that coincide with cancer. However, causation is not established: fewer Inocles might be a consequence of cancer or its treatment, or some third factor might influence both cancer risk and the presence of these DNA rings.
Open questions and future research
Key next steps include functional studies to determine exactly what Inocle genes do in bacterial physiology; experiments to see whether these elements can transfer between bacteria or between people; and longitudinal studies to test whether Inocles influence cancer risk, oral inflammation, or systemic immune responses. The team plans to test how Inocles behave under oxidative stress, whether they can spread via horizontal gene transfer, and how stable they are in different hosts.
Expert Insight
Dr. Lena Morales, microbial geneticist and science communicator: "Finding Inocles is like discovering previously hidden appendices in a book about the oral microbiome. Their size lets them carry complete modules that could change bacterial behavior in clinically meaningful ways. The priority now is to move from correlation to mechanism: controlled lab experiments and carefully designed longitudinal cohorts will tell us whether these rings are bystanders, biomarkers, or active players in health and disease."
Conclusion
Inocles expand our understanding of extrachromosomal DNA in the human microbiome, revealing unusually large plasmid-like rings that are common in mouth-associated Streptococcus. Their gene content suggests roles in stress resistance and DNA repair, and preliminary population data show fewer Inocles in people with head and neck cancers — a correlation that warrants detailed mechanistic follow-up. Advances in sample preparation and sequencing, such as the preNuc approach, were crucial to this discovery and will likely reveal more large-scale genetic elements in other microbiomes. Continued research will determine whether Inocles can be harnessed as biomarkers or therapeutic targets for oral and systemic diseases.
Source: sciencealert
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