Gut bacteria regulate immune system and imbalance triggers
19 June 2012
Genome sequencing has been used to show that the balance of
bacteria in the human gut play a significant role in rheumatoid
Researchers at Mayo Clinic and the University of Illinois at
Urbana-Champaign have found that larger-than-normal populations of
specific gut bacteria may trigger the development of diseases like
rheumatoid arthritis. They may also fuel disease progression in
people genetically predisposed to this crippling and confounding
“A lot of people suspected that gut flora played a role in
rheumatoid arthritis, but no one had been able to prove it because
they couldn’t say which came first — the bacteria or the genes,”
says senior author Veena Taneja PhD, a Mayo Clinic immunologist.
“Using genomic sequencing technologies, we have been able to show
the gut microbiome may be used as a biomarker for predisposition.”
The roughly 10 trillion cells that make up the human body have
neighbours: mostly bacteria that often help, training the immune
system and aiding in digestion, for example. The bacteria in the
intestines, in addition to a relatively small number of other
microorganisms (the gut microbiome), outnumber human cells 10-to-1.
Researchers found that hormones and changes related to aging may
further modulate the gut immune system and exacerbate inflammatory
conditions in genetically susceptible individuals.
Nearly 1% of the world’s population has rheumatoid arthritis, a
disease in which the immune system attacks tissues, inflaming joints
and sometimes leading to deadly complications such as heart disease.
Other diseases with suspected gut bacterial ties include type I
diabetes and multiple sclerosis.
Researchers with the Mayo Illinois Alliance for Technology Based
Healthcare say that identifying new biomarkers in intestinal
microbial populations and maintaining a balance in gut bacteria
could help physicians stop rheumatoid arthritis before it starts.
“This study is an important advance in our understanding of the
immune system disturbances associated with rheumatoid arthritis.
While we do not yet know what the causes of this disease are, this
study provides important insights into the immune system and its
relationship to bacteria of the gut, and how these factors may
affect people with genetic susceptibilities to disease,” says Eric
Matteson, M.D., chairman of rheumatology at Mayo Clinic, who was not
a study author.
Dr. Taneja and her team genetically engineered mice with the
human gene HLA-DRB1*0401, a strong indicator of predisposition to
rheumatoid arthritis. A set of control mice were engineered with a
different variant of the DRB1 gene, known to promote resistance to
rheumatoid arthritis. Researchers used these mice to compare their
immune responses to different bacteria and the effect on rheumatoid
“The gut is the largest immune organ in the body,” says co-author
Bryan White, Ph.D., director of the University of Illinois’
Microbiome Program in the Division of Biomedical Sciences and a
member of the Institute for Genomic Biology. “Because it’s presented
with multiple insults daily through the introduction of new
bacteria, food sources and foreign antigens, the gut is continually
teasing out what’s good and bad.”
The gut has several ways to do this, including the mucosal
barrier that prevents organisms — even commensal or “good” bacteria
— from crossing the lumen of the gut into the human body. However,
when commensal bacteria breach this barrier, they can trigger
autoimmune responses. The body recognizes them as out of place, and
in some way this triggers the body to attack itself, he says.
These mice mimic human gender trends in rheumatoid arthritis, in
that females were about three times as likely to generate autoimmune
responses and contract the disease. Researchers believe these
“humanized” mice could shed light on why women and other demographic
groups are more vulnerable to autoimmune disorders and help guide
development of new future therapies.
“The next step for us is to show if bugs in the gut can be
manipulated to change the course of disease,” Dr Taneja says.