You might imagine that modern medicine has already uncovered all the major secrets of the human body. After all, scientists have mapped the human genome, built advanced imaging systems, and cataloged countless microbes that live within us. Yet, astonishingly, the human body still hides mysteries in the most familiar places—even inside our own mouths.
Researchers from the University of Tokyo and their collaborators have uncovered something entirely new in human biology: Inocles, giant DNA elements that had remained invisible to science until now. These discoveries, published in Nature Communications, reveal a previously unknown layer of complexity in the oral microbiome—the vast community of bacteria and other microbes that live in our mouths.
The finding is more than a scientific curiosity. It changes how we think about the adaptability of bacteria, the hidden strategies that allow them to thrive in constantly shifting environments, and ultimately, the relationship between microbes and human health.
The Renaissance of Microbiome Research
Over the past two decades, science has experienced a renaissance in microbiome research. Much of the attention has centered on the gut microbiome, which influences digestion, immunity, and even mental health. But the mouth, often overlooked, is just as vital. It is home to hundreds of microbial species, forming one of the most diverse ecosystems in the human body.
The oral microbiome is not just about cavities or gum disease. It plays a role in digestion, systemic inflammation, and even cardiovascular health. Yet despite decades of study, many of the molecular tools used by oral bacteria to survive, adapt, and interact with their host remain mysterious. That is why the discovery of Inocles is so striking: it uncovers a hidden dimension to oral biology that was there all along but invisible to conventional scientific methods.
A New Kind of DNA
At first glance, Inocles might sound like something out of science fiction. They are not viruses or bacteria but rather extrachromosomal DNA—large pieces of genetic material that exist in bacteria but outside of their main chromosomes.
Think of a bacterium’s DNA like a central instruction manual. Inocles are like thick add-on booklets stapled to that manual—dense with extra notes, diagrams, and instructions. They are not just decorative; they may hold critical adaptations that bacteria use to survive.
While plasmids, another kind of extrachromosomal DNA, have been known for decades, they are usually small—just a few tens of thousands of base pairs long. Inocles, by contrast, are giants. On average, they measure 350,000 base pairs, making them among the largest genetic elements ever detected in the human microbiome. Their sheer size means they can carry far more genes, giving bacteria new abilities to withstand stress, repair DNA damage, or modify their cell walls to adapt to external pressures.
A Breakthrough in Technology
If Inocles are so large and important, why had no one seen them before? The answer lies in technology. Traditional DNA sequencing techniques work by chopping genetic material into small fragments and then reassembling them. While this works for most microbial DNA, it destroys the ability to reconstruct very large extrachromosomal elements like Inocles.
The breakthrough came when researchers applied long-read sequencing technologies, which can capture continuous stretches of DNA far longer than older methods allow. But even then, human saliva samples posed a challenge because they contain far more human DNA than microbial DNA, drowning out the microbial signals.
Here, innovation made all the difference. Nagisa Hamamoto, co-first author of the study, developed a method called preNuc, which selectively removes human DNA from saliva samples. This gave researchers a much clearer view of microbial genetic material and, for the first time, allowed them to assemble complete Inocle genomes.
What they discovered was remarkable: these enormous DNA elements are hosted by Streptococcus salivarius, a bacterium common in the human mouth and usually considered harmless or even beneficial. Identifying the host, however, was no easy feat, highlighting the hidden complexity of microbial life.
What Inocles Can Do
Although scientists are only beginning to decode the genetic content of Inocles, the early findings are tantalizing. Their large size allows them to carry genes that seem to help bacteria withstand hostile conditions. These include genes for resisting oxidative stress, repairing DNA damage, and modifying the bacterial cell wall—mechanisms that could be crucial for surviving the ever-changing environment of the human mouth.
This suggests that Inocles are not passive passengers. They may be active partners, equipping bacteria with the tools they need to thrive. By doing so, they may indirectly shape human oral health, influencing whether bacteria contribute to beneficial balance or tip the scales toward disease.
Implications for Oral and General Health
The discovery of Inocles raises profound questions about how we understand oral health. Could these giant DNA elements influence the likelihood of developing cavities or gum disease? Might they help explain why some bacteria persist in the mouth despite brushing, rinsing, and antibiotics? Could they even serve as biomarkers for systemic diseases, including cancer, as some preliminary hints suggest?
If 74% of humans carry Inocles, as the study estimates, they are not rare oddities—they are a widespread, fundamental feature of human biology. This means that understanding them could unlock new ways to prevent or treat disease, perhaps by targeting specific bacterial adaptations or using Inocles themselves as diagnostic tools.
The Next Steps in Research
The University of Tokyo team is now working to culture bacteria that contain Inocles, which will allow them to study their function more directly. Culturing is crucial because it opens the door to experiments that reveal how these DNA elements behave, whether they can transfer between bacteria, and how they influence microbial communities over time.
Computational tools like AlphaFold, which predicts protein structures, will also play a role. Since many of the genes carried by Inocles are still uncharacterized, simulations may help reveal what kinds of proteins they produce and what roles those proteins play.
Together, these approaches could eventually map out the “hidden instructions” encoded in Inocles, turning them from mysterious newcomers into a central part of microbiome science.
A Reminder of How Much We Don’t Know
Perhaps the most profound lesson from the discovery of Inocles is humility. For all the progress science has made, for all the sequencing projects and global collaborations, something so large and so common remained invisible until now—simply because we lacked the tools to see it.
This is not the first time the human body has surprised us. In recent years, scientists have identified new organs and new microbial species, each reshaping our understanding of biology. Inocles are part of this same story: a reminder that the human body is not fully mapped, that our microbiomes are still terra incognita, and that the frontier of discovery remains open.
The Mouth as a Microbial Universe
Your mouth may seem ordinary, but it is a bustling universe of life. Every sip of water, every bite of food, every breath introduces new challenges for the microbes that live there. The discovery of Inocles shows us that these microbes are not passive residents but resourceful survivors, equipped with powerful genetic tools we are only just beginning to understand.
And so, tucked inside our saliva, hidden in plain sight, lies a new chapter in the story of human biology. It is a story of invisible allies and potential threats, of evolutionary ingenuity and scientific discovery. Most of all, it is a story that reminds us how much wonder still resides within us, waiting for the right questions and the right tools to bring it into the light.
More information: Yuya Kiguchi et al, Giant extrachromosomal element “Inocle” potentially expands the adaptive capacity of the human oral microbiome, Nature Communications (2025). DOI: 10.1038/s41467-025-62406-5
