Mouth bacteria have been associated with severe forms of inflammatory bowel disease
The human body is a league of nations for an unfathomable variety of microbes that are kept under control by complex relationships with our immune system and carefully designed truces.
From time to time, members of this microscopic community develop a propensity for invasion and cause chaos as they flow across borders. For people with severe inflammatory bowel disease (IBD), a strain of oral bacteria could do just that.
A genetic analysis of more than a dozen strains of a common bacterium, Campylobacter concisus, has revealed a short DNA sequence that could explain why this type at home in the mouth is a law-abiding citizen but a potential terrorist in the gut.
“Oral bacteria enter the digestive system every day when we swallow food or saliva,” says biomolecular scientist Li Zhang of the University of New South Wales (UNSW), Australia.
“Most bacteria are killed by stomach acids, but some can survive and settle in the intestines. The bacteria may not have settled for long, but the mouth is constantly bringing in new bacteria – that’s the problem.”
In general, many microbes of the genus Campylobacter are bad news for the human digestive system. If you’ve ever had an upset stomach that made you run to the toilet during a vacation overseas, there’s a good chance that this tiny horror is behind it.
Since such disease-causing species are usually found in the intestines of other animals, we tend to absorb them by eating contaminated meat or water.
C. concisus is not quite like its more pathogenic cousins. We can call this species our own and in practically all healthy people it lives happily under an ocean of spit.
In recent years, however, medical researchers have suspected that C. concisus may not always be the peaceful citizen we expected. Bacterial markers associated with the microbe are suspiciously linked to active incidences of Crohn’s disease, for example.
Together with ulcerative colitis, Crohn’s disease falls into a category of IBD characterized by severe inflammation of the intestinal wall and surrounding tissues. The result is everything from diarrhea and discomfort to blood in the stool, excruciating pain and weight loss.
In cases where medication or lifestyle changes do little to help, surgery may be required, making it a serious disease to deal with.
What exactly causes these inflammatory bowel diseases in the first place is not entirely clear. It is believed that diet and stress only exacerbate the symptoms, with genetics, drugs and the environment playing a potential role in their development.
What is clear is that this is a complex condition. Clinical studies increasingly suggest that at least some strains of C. concisus are associated, although establishing guilt requires much more evidence.
For some potentially pathogenic strains, the entire genome has already been analyzed, but so far there have been no genomes of healthy individuals to which they could be compared.
In this latest study, a further 13 genomes were successfully assembled from C. concisus strains taken from both healthy controls and individuals with inflammatory bowel disease.
This handful of DNA libraries provided the team with a basis to compare the genetics of more than 230 strains collected from 146 people around the world. Among them were 120 strains from patients with Crohn’s disease and severe ulcerative colitis, some of whom underwent surgery for their disease.
From this wealth of genetic data, the researchers have identified common details.
One tiny DNA ring called plasmid stood out – a sequence of only two genes encoding pSma1.
“A plasmid is located outside the chromosomal DNA of the bacteria,” says Fang Liu, the lead author of the study, a biotechnology researcher at the UNSW.
“It is considered a mobile genetic element, which means that it can be transferred between different strains of the bacterium or even between different species. If the plasmid carries any virulence genes, the bacteria could acquire this virulence.”
Although the plasmid was small, it was found in large numbers in C. concisus strains taken from people with inflammatory bowel disease, especially those with ulcerative colitis.
That is, it has also been identified in two strains taken from a pair of healthy controls, suggesting that the story is probably far more complicated than having only one interfering strain of the bacterium.
Further research will help to unravel the mechanisms at work. While it is possible that pSma1 allows C. concisus to exploit an already inflamed intestine, its potential role in antagonizing, if not the onset of the disease, would pave the way for further treatments.
For the estimated 6.8 million people worldwide who struggle with the symptoms of IBD, the discovery could be life-changing.
“If we find that the plasmid plays a role in the pathogenesis, it could be fairly easy to translate this finding into clinical application,” says Zhang.
“Treatments that target the oral cavity could help reduce the burden on the bacteria. We may not be able to eradicate this bacterium, but we could certainly reduce the burden.
This research was published in Microbial Genomics.
