Science Sub-Journal: Another important function of gut bacteria? Causes rheumatoid arthritis

Researchers at the University of Colorado School of Medicine have found that a unique bacterium found in the gut may be responsible for triggering rheumatoid arthritis (RA), an autoimmune disease that is inherently at risk
.

Dr.
Kristine Kuhn, associate professor of rheumatology, led a team of researchers from the Department of Rheumatology to conduct the study, which was published Oct.
26 in the journal Science Translational Medicine
.

This work was established by Kevin Deane, Kristen Demuelle, and Mike Holers, among others, to determine which people are at risk for rheumatoid arthritis based on serological markers that can remain in the blood for many years
before diagnosis.
"When they look at these antibodies, one is the normal type of antibody that we usually see in circulation, but the other is the antibody that we usually associate with our mucosa, whether it's the oral mucosa, the intestinal mucosa, or the lung mucosa
.
" We began to wonder, "Is there something at the mucosal barrier that causes rheumatoid arthritis?"

A new bacterium was discovered

With the help of a team led by Bill Robinson, M.
D.
, of Stanford University, the researchers took antibodies produced by immune cells from individuals whose blood markers showed they were at risk and mixed them with the feces of individuals at risk to look for antibody-labeled bacteria
.

To further test their hypothesis, the researchers used animal models to host the newly discovered bacteria
.
These experiments showed that the bacteria not only produced the blood markers found in individuals at risk of rheumatoid arthritis in animal models; But some models also show the full development of
rheumatoid arthritis.

"Our collaborators confirmed that T cells in the blood of rheumatoid arthritis patients respond to these bacteria, while healthy people do not
.
Through studies in human and animal models, we were able to determine that these bacteria are associated
with the risk of developing rheumatoid arthritis.
They cause diseases of rheumatoid arthritis in animal models, while in humans we can show that this bacterium appears to trigger a specific immune response
against rheumatoid arthritis.
”

A new target for rheumatoid arthritis

If this unique bacterium does drive the immune response in individuals at risk of causing rheumatoid arthritis, Kuhn said, it may be possible to target the bacteria with drugs to stop that reaction from happening
.

"Our next step is to determine whether these bacteria are associated with other genes, the environment, and mucosal immune responses in larger populations at risk for rheumatoid arthritis, and ultimately determine the development of
rheumatoid arthritis," Kuhn said.
Then we can say, 'This is a marker that helps predict who will develop rheumatoid arthritis,' and apply prevention strategies
.
" Another opportunity is that if we can understand how it triggers these immune responses, we may be able to block the bacteria's ability
.
”

Study the triggering mechanism

Kuhn said the study took five years to conduct and analyze and was helped
by a number of people who found themselves at risk for rheumatoid arthritis and volunteered to support the research.
Ultimately, the researchers want to study how the bacteria triggers an immune response, and different ways to
prevent that from happening.

"There are a lot of different techniques that are just beginning to emerge that can selectively target bacteria in the gut microbiome, for example, to prevent it from having immunogenic effects
on the host.
" "For a long time, it has been thought that antibiotics may be an effective treatment for rheumatoid arthritis, but unlike the sledgehammer effect of traditional antibiotics, which destroy a large host of bacteria, we may be able to selectively target this bacteria or its effects
.
"

Journal Reference:

1. Meagan E.
   Chriswell, Adam R.
   Lefferts, Michael R.
   Clay, Alex Ren Hsu, Jennifer Seifert, Marie L.
   Feser, Cliff Rims, Michelle S.
   Bloom, Elizabeth A.
   Bemis, Sucai Liu, Megan D.
   Maerz, Daniel N.
   Frank, M.
   Kristen Demoruelle, Kevin D.
   Deane, Eddie A.
   James, Jane H.
   Buckner, William H.
   Robinson, V.
   Michael Holers, Kristine A.
   Kuhn.
   Clonal IgA and IgG autoantibodies from individuals at risk for rheumatoid arthritis identify an arthritogenic strain of            Subdoligranulum.
   Science Translational Medicine, 2022; 14 (668) DOI: 10.
   1126/scitranslmed.
   abn5166