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FORSYTH RESEARCHERS REVEAL THAT ORAL TM7 BACTERIA MAY PROTECT HUMANS FROM
PATHOGENIC BACTERIA



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A group of bacteria called TM7 live in the human body by growing on the surfaces
of other microbes, known as host bacteria. Ever since this arrangement was
discovered, many scientists have assumed TM7 were harmful to humans, while their
host bacteria were health promoting. Studies have shown higher abundance of TM7
in diseases including vaginosis, inflammatory bowel disease, and periodontitis,
and lower abundance of host bacteria, further suggesting TM7 are pathogenic. But
a new paper published today by Forsyth Institute researchers and their
colleagues finds the opposite effect—TM7 decreased periodontal inflammation and
bone loss in a mouse model.  

The paper, Episymbiotic Saccharibacteria suppresses gingival inflammation and
bone loss in mice through host bacterial modulation, was published online today
in the journal Cell Host & Microbe. It describes the first time TM7 has been
systematically cultured from human periodontal disease samples, isolated from
their host bacteria, and studied in an animal model.

Dr. Batbileg Bor, Assistant Member of Staff at The Forsyth Institute and
corresponding author of the paper, said he and his team took plaque samples from
patients with gum disease and isolated multiple species of TM7 bacteria from the
samples. To understand how TM7 impacts bone loss and inflammation, they devised
an experiment with three groups of mice. In one group, a clean ligature was
placed around one of the mouse’s molars, establishing a baseline. In the second
group, the ligature was soaked in TM7’s host bacteria alone and then wrapped
around the molar. In the third group, researchers soaked the ligature in TM7’s
host bacteria, plus TM7 bacteria from the periodontal samples, and then placed
it on the molar.

“Our findings were the opposite of what we and others expected,” Bor said. The
mice fitted with the ligatures soaked in TM7’s host bacteria alone experienced
more intense bone loss and inflammation than the established baseline, while the
mice that got ligatures with TM7 experienced a decrease in bone loss and
inflammation.

The study, published online today in the journal Cell Host & Microbe, finds that
TM7 decreased periodontal inflammation and bone loss in a mouse model.

This finding turns upside down the idea that TM7 are pathogenic and their host
bacteria are health associated. In fact, Bor says he now believes TM7 may be
protective against disease, while their host bacteria are the harmful ones.

Co-authors of the paper include Postdoctoral Research Fellow Deepak Chouhan and
Research Associate Otari Chipashvili from Forsyth, as well as Daniel Utter, a
Postdoctoral Researcher at California Institute of Technology.

The researchers discovered two important mechanisms TM7 are modulating in the
mouse model to reduce inflammation and bone loss, both by altering the behavior
of their host bacteria. The first is decreased production of a collagen binding
protein in the host bacteria, where collagen is commonly found in the network of
molecules that form tissues. The second is disruption of the host bacterial
metabolism in the inflammatory environment, which TM7 accomplish by shutting
down the genes that break down sialic acid, one of the most common carbohydrates
that coats the surface of many human cells.

“From these findings, we are debunking the previous hypothesis that TM7 are
pathogenic and bad for you while the host bacteria are good and health
associated. We think it might actually be the other way around,” Bor said.

TM7 are ultrasmall bacteria with tiny genomes that need to live off other
organisms to survive. They are found in humans and other mammals, soil, water,
and many other varied environments. There are dozens of different species within
the TM7 phyla, and TM7 is one of 73 different phyla under the Candidate Phyla
Radiation lineage. Most of the bacteria within this group have yet to be
cultured in the lab and therefore remain a mystery to scientists, despite
representing more than 25 percent of all bacterial diversity on Earth. 

Previous studies have found TM7 in the dental tartar of human ancestors,
suggesting these bacteria have been coevolving with humans for thousands of
years.

Co-authors of the paper include Dr. Batbileg Bor, Assistant Member of Staff at
Forsyth. Postdoctoral Research Fellow Deepak Chouhan and Research Associate
Otari Chipashvili from Forsyth, as well as Daniel Utter, a Postdoctoral
Researcher at California Institute of Technology

“You can infer that TM7 are part of your extended immune system. It’s like a
protective part of you that is just hanging out in your mouth, and when there is
inflammation, it can try to reduce that,” Chipashvili explained.

While this research is still in early stages, Bor hopes to ultimately harness
TM7 to promote better oral health. One potential application would be similar to
phage therapy, or the use of bacterial viruses to kill pathogenic bacteria
without needing drugs or antibiotics.

“If our hypothesis is proven right, TM7 could function in the same way, but
there is a lot that needs to be done before we can get to that stage,” Utter
said. “Culturing these bacteria and understanding their genome was the first
major step. This new study marks another major step as the first in vivo
experimental study to upend previous notions of TM7’s role in health and disease
of oral microbial communities. We are looking forward to what may come out of
these studies.”

Learn more about the Bor Lab.

Register for the virtual Forsyth Institute Scientific Symposium: Oral
Microbiome—Beyond Bacteria.




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