The oral microbiome, which is collectively known as microbes in our mouths, has many effects on our overall health that we are still not fully understanding. Some bacteria can cause inflammation that can lead to periodontitis, as well as other systemic diseases such diabetes and cardiovascular disease. Other oral organisms have been linked with certain types of carcinoma. Scientists are trying to understand how these microbes interact and how they affect our bodies in order to discover their roles in health and disease.
One group that belongs to Candidate Phyla Radiation is one of the many bacterial species found in our mouths. These bugs are unusual because they are small and live in a unique relationship with their host bacteria. Only one group of bacteria from the CPR has been studied in depth, a group called TM7. This group was first cultivated by Dr. Xuesong He at Forsyth Institute in 2014.
Dr. Dr. Jeffrey S. McLean from the University of Washington was his collaborator and they developed a new system using the first human oral TM7x strain, Actinomyces odontolyticus. The model system was used by researchers to experimentally study the tiny bacteria. They tested a hypothesis about how TM7 adapts to life inside humans and provided empirical data to support previous genomic studies. Today, their findings were published in the journal. Proceedings of the National Academy of Sciences.
Scientists have found TM7 within many environments, including soil, groundwater, as well as the bodies of other mammals. Studies have shown that, while the genomes of humans are very similar, the TM7 found inside human mouths is unique to those found in other environments. This is because they have a gene cluster encoding ADS, the arginine desiminase system.
“This was intriguing to us since there seem to be very few genomic changes that occurred in this group of tiny bacteria with already small genomes as they transitioned from the environment to mammals,” said Dr. McLean.
Researchers speculated that TM7 acquired ADS to aid them in adapting and surviving in the human oral cavity. To test this hypothesis, Dr. Jing “Janet” Tian, first author of the study, used the model system to experimentally investigate the function and impact of ADS on TM7x and its host bacterium. ADS helped TM7x to break down arginine. This process produces the compounds Adenosinetriphosphate (ATP), as well as ammonia. TM7x was able to multiply more easily due to the increased amount of ATP, and ammonia. It also protected TM7x from acid stress, a condition that microbes commonly encounter in the human mouth cavity as a result of the acid made when bacteria metabolize dietary carbs.
The experiment proved that TM7x survived in the experimental environment for longer periods of time than they could without ADS.
“Most of the current studies on CPR bacteria are based on a culture-independent genomic approach. Using this TM7 bacterial model system, we are able to directly test a hypothesis generated from genome analysis, which helps move the CPR research field from genome-focused studies toward hypothesis-driven studies to better understand their biology,” said Dr. He.
“The production of ammonia through TM7-encoded ADS raises the pH level in the human oral microenvironment, which poses an intriguing question about the role of TM7 in the development of dental caries,” said Dr. Tian, a Pediatric Dentist at Peking University Hospital of Stomatology and visiting scholar at Forsyth. Dr. Tian previously found that children with dental caries had a significantly higher abundance of TM7 after they were treated. “We think this indicates that TM7 may be more associated with a caries-free state, and we are planning to do more research in this area,” Dr. Tian said.
This study adds to a growing body evidence that TM7 bacteria may play a greater protective role in oral hygiene than originally thought. Scientists believe that TM7 bacteria is responsible for periodontal disease. For example, TM7 levels are found to be high in patients with periodontal disease. A recent study led by Dr. Batbileg Bor of Forsyth found the opposite effectTM7 reduced periodontal inflammation, bone loss, and bone loss in a mouse model.
“We are still in the early stages of understanding how each of the many different types of these ultrasmall parasitic bacteria, which we basically just uncovered within humans, are impacting health and disease,” said Dr. McLean.
“That’s why it’s so important to have a bacterial model system to not only achieve better understanding of the unique lifestyle of TM7, but experimentally test whether the hypotheses based on genomic studies or clinical observation actually stands,” Dr. He agreed. “Now, we have a manipulatable model system for TM7, which is truly a major advantage.”
Ultra-small, parasitic bacteria found in groundwater, moose… and you
Otari Chipashvili, et al. Episymbiotic Saccharibacteria suppresses gingival swelling and bone loss in mice by host bacterial modulation. Cell Host and Microbe (2021). DOI: 10.1016/j.chom.2021.09.009
The epiparasitic Saccharibacteria and the host bacteria in a mammalian niche environment benefit from the acquisition of arginine desiminase systems. Proceedings of the National Academy of Sciences (2022). DOI: 10.1073/pnas.2114909119.
Researchers gain insight into how ultrasmall bacteria in the environment have adapted and now live inside humans (2022, Jan 3)
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