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Mysterious pieces of DNA called ‘inocles’ could be hiding in your mouth

Ethan Davis by Ethan Davis
October 14, 2025
in Science & Environment
Reading Time: 4 mins read
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Scientists have discovered huge and mysterious pieces of DNA in the oral microbiota – the population of bacteria and other microbes living in our mouths – and they say this giant DNA could influence the human immune system.

It is well known that we have a lot of bacteria in our mouths and that these microbes can have both positive and negative impacts on our oral and overall health.

Now, in a study published August 11 in the journal Natural communicationsresearchers report a previously unknown feature of the oral microbiome: giant chunks of bacterial DNA that separate from the microbes’ main genome. Additionally, these pieces of DNA are associated with changes in the body’s immune system and even the onset of certain types of cancer, the team found.

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The study provides a “new puzzle piece that is a step forward in understanding the oral microbiome, human health and human disease.” Floyd Dewhirsta professor at the ADA Forsyth Institute who was not involved in the research told Live Science in an email.

Microbiome studieswhich have flourished over the past decade, have shown that the body’s microbiomes play a major role in human health and disease. Researchers have identified the types and proportions of different microbial species that live in places like our mouths And gutsthen used this data to see how differences between these characteristics relate to our health.

Over the years, the genomes of these species have been studied in depth, but conventional genetic analyzes have not yet been able to explain all the links between our microbiome and our general health.

Researchers in the Yutaka Suzuki A laboratory at the University of Tokyo wanted to explore this missing data and was inspired by the recent discovery of giant extrachromosomal elements (GEEs) in soil-dwelling bacteria. ECEs are pieces of DNA distinct from the main genome of an organism. In humans, our mitochondrial DNA – stored in the power plants of our cells – is an ECE. In bacteria, a small, commonly known ECE is called a plasmid.

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Lead author of the study Yuya Kiguchiwho is now a researcher at Stanford University, and his colleagues in the Suzuki lab predicted that giant ECEs could be found in bacteria living elsewhere than in soil.

“Maybe a lot of these giant extrachromosomal elements are found in the environment, in the microbiome realm, or in pathogens,” Kiguchi told Live Science. “But we don’t know of any examples of this type of giant extra-chromosomal element coming from the (human) commensal microbiome.” Commensal microbes are those that live symbiotically in or on the human body.

Using saliva samples from hundreds of people, researchers discovered, for the first time, that giant ECEs also exist in our oral microbiome. The research team called these giant pieces of DNA “inocles”; the name means “Incoded crimp sequence; oreal origin; cirkey genomic structure. » They also found that about 74% of people in their study had these inocles in their oral microbiome.

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So why is this the first time that inocles have been discovered? Most genetic experiments on bacteria use short-read DNA sequencing methods. This involves cutting a cell’s DNA into smaller pieces, reading their code, and then putting those pieces together to form a complete genome using a computer. Although this sequencing method can easily detect small ECEs, such as typical bacterial plasmids, inocles are too large and complex to be spotted by short-read sequencing.

Using long-read DNA sequencing – a more expensive and time-consuming method in which much larger pieces of DNA are sequenced and assembled – scientists were able to identify these large pieces of extrachromosomal DNA in bacteria from human saliva samples. By correlating these results with blood samples from the same people, they also discovered that differences in inocle levels are associated with differences in the immune system, including the immune response to certain bacterial and viral infections.

Sixty-eight people in the study had either a type of head and neck cancer or colorectal cancer, and these people had lower levels of inocles in their oral microbiome compared to people without these cancers. This raises the possibility of using these newly discovered giant pieces of DNA as future cancer biomarkers, the study authors suggested.

As a next step, the researchers aim to cultivate these inocles in the laboratory so that they can study their function and how they can spread between bacteria and humans in more detail.

“Now that we know that inocles exist, we can try to understand their functions and potential roles in health and disease,” Dewhirst said.

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