Although scientists have already gathered a wealth of information about the gut microbiome, the oral microbiome remains a relatively unexplored territory. For example, researchers recently discovered massive DNA fragments in the mouth that were previously unknown.

You may already know that inside the nuclei of nearly every cell in the human body, DNA spirals intertwine, serving as blueprints that govern our existence. But you might not have heard that some cells also contain floating DNA fragments that are not part of the double helix. These separate genetic elements are called extrachromosomal DNA (ecDNA). They can play a role in the development and growth of cancerous tumors and may also help maintain telomeres—the protective caps at the ends of chromosomes associated with aging.

While investigating the presence of ecDNA in human saliva, researchers from the University of Tokyo were astonished by the results of their new study. They found ecDNA in the oral microbiome, hidden within Streptococcus salivarius bacteria, and these fragments turned out to be remarkably large. The scientists named them "Inocles."

"We know that the oral microbiome contains many different types of bacteria, but many of their functions and how they work are still unknown," says lead author Yuya Kiguchi. "By studying this, we discovered Inocles—an example of extrachromosomal DNA. It's like finding a book with extra notes attached, and we're just beginning to read them to understand what they do."

To uncover this previously unknown genetic material, the researchers developed their own method for mapping DNA found in human saliva samples used in the study. Instead of focusing on fragmented genetic data, which is usually obtained in such analyses, they created a technique to capture much longer DNA chains, which they called preNuc. This method allowed them to detect Inocles inside oral bacteria.

"The average size of an Inocle genome is 350,000 base pairs—a unit of length for genetic sequences—making it one of the largest extrachromosomal genetic elements in the human microbiome," notes Kiguchi. "Plasmids, other forms of extrachromosomal DNA, usually reach only a few tens of thousands of base pairs. This length allows Inocles to carry genes for various functions, including resistance to oxidative stress, DNA repair, and genes related to the cell wall, possibly involved in adaptation to external stress."

However, researchers are still not entirely sure what specific role these large ecDNA blocks play and plan to conduct further studies to investigate them—especially the uncharacterized genes they contain. This work could lead to a better understanding of how Inocles affect overall oral health and whether they might contribute to or prevent the development of cavities and gum disease.

"Remarkably, considering the diversity of the human population represented in the saliva samples, we estimate that 74% of all people may have Inocles," Kiguchi concludes. "And although the oral microbiome has been studied for a long time, Inocles remained hidden all this time due to technological limitations."

Now that we know they exist, we can begin to explore how they shape the relationships between humans, their microbes, and oral health. There are even hints that Inocles could serve as markers for serious diseases, such as cancer.