Recent research has discovered that numerous circular DNA structures carried by oral bacteria may benefit oral health and the immune system, thereby reducing the risk of certain cancers.
These newly discovered DNA structures, called “inocles,” are large plasmids—genetic elements that exist outside the main DNA of many microorganisms.
A research team led by researchers at the University of Tokyo found that inocles may play a crucial role in helping bacteria, particularly Streptococci, adapt to the oral environment, acting like an extra survival kit.
“We know that the oral microbiome contains many different bacteria, but many of their functions and how they perform them remain unknown,” said microbiologist Yuya Kiguchi.
“Through our exploration, we discovered inocles, which are an example of extrachromosomal DNA—DNA that exists outside the cell’s main genetic material.”
These large circular DNA structures were discovered by carefully studying saliva samples from 56 volunteers. A further 476 samples were tested to determine the prevalence of inocles in the general population. The data suggest that approximately three-quarters of people may carry these genetic elements.
One reason inocles were previously overlooked is their size. Traditional DNA sequencing methods require cutting DNA into smaller fragments, making it easier to read but more difficult to reconstruct larger sequences.
To address this issue, researchers developed a custom sequencing system called preNuc that removes human DNA from samples, reducing the number of bacterial DNA fragments that need to be screened.
On average, an inocles genome is approximately 350 kilobases long, making it one of the largest extrachromosomal genetic elements in the human microbiome.
“Plasmids and other forms of extrachromosomal DNA are typically only a few tens of kilobases long,” Kiguchi explained. The length of inocles allows them to contain multiple genes that may contribute to resistance to oxidative stress, DNA repair, and cell wall function, potentially helping bacteria adapt to external stresses.
Surprisingly, the levels of these DNA elements were significantly lower in the saliva of patients with head and neck cancer, suggesting that inocles may have a protective effect.
Whether inocles protect against cancer or whether a reduction in these elements increases cancer risk remains uncertain.
The researchers are eager to further investigate how Inocles genes function, whether they can be transmitted between individuals, and their potential impact on oral health.
“It’s like finding a book with extra footnotes—we’re just beginning to read through them to understand their role,” Kiguchi said.