Rheumatoid arthritis linked to specific bacteria in intestine
8 November 2013
For the first time in humans, a species of intestinal bacteria,
Prevotella copri, has been linked to the chronic
inflammatory joint disease rheumatoid arthritis.
The new findings by the NYU School of Medicine in the US, add to
the growing evidence that the microbes in our body play an important
role in regulating our health.
The researchers used DNA analysis to compare gut bacteria from
faecal samples of patients with rheumatoid arthritis and healthy
individuals, the researchers found that P. copri was more
abundant in patients newly diagnosed with rheumatoid arthritis than
in healthy individuals or patients with chronic, treated rheumatoid
arthritis. Moreover, the overgrowth of P. copri was
associated with fewer beneficial gut bacteria belonging to the
“Studies in rodent models have clearly shown that the intestinal
microbiota contribute significantly to the causation of systemic
autoimmune diseases,” says Dan R. Littman, MD, PhD, the Helen L. and
Martin S. Kimmel Professor of Pathology and Microbiology and a
Howard Hughes Medical Institute investigator.
“Our own results in mouse studies encouraged us to take a closer
look at patients with rheumatoid arthritis, and we found this
remarkable and surprising association,” says Dr. Littman.
“At this stage, however, we cannot conclude that there is a
causal link between the abundance of P. copri and the onset
of rheumatoid arthritis,” Dr. Littman says. “We are developing new
tools that will hopefully allow us to ask if this is indeed the
The new findings, reported in the open-access journal eLife, were
inspired by previous research in Dr. Littman’s laboratory,
collaborating with Harvard Medical School investigators, using mice
genetically predisposed to rheumatoid arthritis, which resist the
disease if kept in sterile environments, but show signs of joint
inflammation when exposed to otherwise benign gut bacteria known as
segmented filamentous bacteria.
Rheumatoid arthritis, an autoimmune disease that attacks joint
tissue and causes painful, often debilitating stiffness and
swelling, affects 1.3 million Americans. It strikes twice as many
women as men and its cause remains unknown although genetic and
environmental factors are thought to play a role.
The human gut is home to hundreds of species of beneficial
bacteria, including P. copri, which ferment undigested
carbohydrates to fuel the body and keep harmful bacteria in check.
The immune system, primed to attack foreign microbes, possesses the
extraordinary ability to distinguish benign or beneficial bacteria
from pathogenic bacteria. This ability may be compromised, however,
when the gut’s microbial ecosystem is thrown off balance.
“Expansion of P. copri in the intestinal microbiota
exacerbates colonic inflammation in mouse models and may offer
insight into the systemic autoimmune response seen in rheumatoid
arthritis,” says Randy S. Longman, MD, PhD, a post-doctoral fellow
in Dr. Littman’s laboratory and a gastroenterologist at
Weill-Cornell, and an author on the new study. Exactly how this
expansion relates to disease remains unclear even in animal models,
Why P. copri growth seems to take off in newly diagnosed
patients with rheumatoid arthritis is also unclear, the researchers
say. Both environmental influences, such as diet and genetic factors
can shift bacterial populations within the gut, which may set off a
systemic autoimmune attack. Adding to the mystery, P. copri
extracted from stool samples of newly diagnosed patients appears
genetically distinct from P. copri found in healthy
individuals, the researchers found.
To determine if particular bacterial species correlate with
rheumatoid arthritis, the researchers sequenced the so-called 16S
gene on 44 faecal DNA samples from newly diagnosed patients with
rheumatoid arthritis prior to immune-suppressive treatment; 26
samples from patients with chronic, treated rheumatoid arthritis; 16
samples from patients with psoriatic arthritis (characterized by
red, flaky skin in conjunction with joint inflammation); and 28
samples from healthy individuals.
Seventy-five percent of stool samples from patients newly
diagnosed with rheumatoid arthritis carried P. copri
compared to 21.4% of samples from healthy individuals; 11.5% from
chronic, treated patients; and 37.5% from patients with psoriatic
Effect of medication
Rheumatoid arthritis is treated with an assortment of
medications, including antibiotics, anti-inflammatory drugs like
steroids, and immunosuppressive therapies that tame immune
reactions. Little is understood about how these medications affect
gut bacteria. This latest research offers an important clue, showing
that treated patients with chronic rheumatoid arthritis carry
smaller populations of P. copri.
“It could be that certain treatments help stabilize the balance
of bacteria in the gut,” says Jose U. Scher, MD, director of the
Microbiome Center for Rheumatology and Autoimmunity at NYU Langone
Medical Center’s Hospital for Joint Diseases, and an author on the
new study. “Or it could be that certain gut bacteria favour
The researchers plan to validate their results in regions beyond
New York, since gut flora can vary across geographical regions, and
investigate whether the gut flora can be used as a biological marker
to guide treatment.
“We want to know if people with certain populations of gut
bacteria respond better to certain treatment than others,” says Dr.
Scher. Finally, they hope to study people before they develop
rheumatoid arthritis to see whether overgrowth of P. copri
is a cause or result of autoimmune attacks.