Inocles DNA Loops in Mouth Bacteria May Benefit Oral Health

Huge loops of DNA found in bacteria that live in the mouth could benefit oral health and the immune system, potentially lowering the risk of some cancers.

Known as ‘Inocles’, these newly identified nucleic-acid rings seem to be an unusually large form of plasmid - genetic material that sits outside the primary DNA blueprint of many microbes.

Inocles and mouth bacteria

A research team led by scientists at the University of Tokyo suggests that Inocles may be important in helping bacteria, specifically Streptococcus species, adjust to the mouth’s biological conditions. In effect, they may act as supplementary survival toolkits.

“We know there are a lot of different kinds of bacteria in the oral microbiome, but many of their functions and means of carrying out those functions are still unknown,” says University of Tokyo microbiologist Yuya Kiguchi.

“By exploring this, we discovered Inocles, an example of extrachromosomal DNA – chunks of DNA that exist in cells, in this case bacteria, but outside their main DNA.”

The vast DNA rings emerged during a detailed analysis of saliva from 56 volunteers. The researchers then examined a further 476 samples to establish how widespread Inocles are in the wider population. Their data indicates that roughly three-quarters of people may carry these elements.

A sequencing method for giant DNA loops

Paradoxically, Inocles may have escaped detection because they are so exceptionally large. Standard DNA-sequencing methods cut DNA into smaller pieces. While these fragments are simpler to read, assembling large sequences from them is more difficult.

To overcome this, the team developed a tailored sequencing approach, called preNuc. It removed human DNA from each sample, leaving fewer bacterial-DNA puzzle pieces to sort through.

“The average genome size of [an] Inocle is 350 kilobase pairs, a measure of length for genetic sequences, so it is one of the largest extrachromosomal genetic elements in the human microbiome,” says Kiguchi. “Plasmids, other forms of extrachromosomal DNA, are at most a few tens of kilobase pairs.”

“This long length endows Inocles with genes for various functions, including resistance to oxidative stress, DNA damage repair and cell wall-related genes, possibly involved in adapting to extracellular stress response.”

Possible links between Inocles and cancer

Notably, people with head and neck cancer in the larger saliva-sample group had substantially fewer of these DNA elements in their mouths. This points to a possible benefit from the loops. However, it remains unclear whether Inocles help protect against cancer, or whether another factor both lowers Inocles numbers and increases cancer risk.

The researchers also want to investigate how Inocles genes work, whether the elements can pass between people, and the effects they may have on oral health.

“It's like finding a book with extra footnotes stapled to it, and we're just starting to read them to find out what they do,” says Kiguchi.

The study was published in Nature Communications.