Gut-residing bacteria trigger arthritis in genetically susceptible individuals

Jun 17, 2010 by Mary Bates

A single species of bacteria that lives in the gut is able to trigger a cascade of immune responses that can ultimately result in the development of arthritis.

Our gut, like that of most mammals, is filled with thousands of species of bacteria, many of which are helpful and aid in the development of a normal, healthy immune system. Gut-residing bacteria can also play a role in disorders of the immune system, especially in which the body attacks its own cells.

It turns out that is one such disorder. Researchers in the laboratories of Christophe Benoist and Diane Mathis at Harvard Medical School and Dan Littman at New York University made this discovery while working in mice prone to arthritis.

"In the absence of all bacteria, these mice didn't develop arthritis, but the introduction of a single was enough to jump-start the immune process that leads to development of the disease," says Mathis, an HMS professor of pathology.

The findings appear in the June 25 issue of the journal Immunity.

The researchers began by raising arthritis-prone mice in a germ-free environment. The mice had much lower levels of arthritis-causing autoantibodies than mice raised in a non-germ-free facility. The germ-free mice also showed strong attenuation in the onset and severity of clinical arthritis.

At three weeks of age, some mice were transferred to a non-germ-free facility and the researchers introduced segmented filamentous bacteria into their systems. When they introduced this normally-occurring bacteria into the mice, the animals rapidly began producing autoantibodies and developed arthritis within four days.

First author Hsin-Jung Wu emphasizes that these bacteria do not cause the mice to "catch" arthritis. "It's more that they have the , and this bacterium creates an environment that allows this genetic susceptibility to play out," says Wu, a postdoctoral researcher at Harvard Medical School. "It's an interaction between genetics and the environment."

The team mapped out the complex chain of events leading to arthritis. The segmented filamentous bacteria cause the animals to produce more of a particular subset of T cells. The immune system reacts to the activity of the T cells as if to a foreign threat and produces autoantibodies that trigger the devastating disease.

One surprising finding was that bacteria in the gut could influence the development of an autoimmune disease affecting tissues distant from the gut. Diseases such as irritable bowel syndrome have been linked to gut-residing bacteria, but this study is unique in showing the mechanism by which a bacterium in the gut can influence the development of an autoimmune response that ends in inflammation and pain in the joints.

The team will continue to use this mouse model of arthritis to answer questions about the link between the disease and autoimmune response. Next, they plan on tackling the molecular explanation of how these bacteria promote the development of this particular subset of T cells and to explore connections with other autoimmune diseases, in particular type-1 diabetes.

Explore further: Diet affects men's and women's gut microbes differently

add to favorites email to friend print save as pdf

Related Stories

Unusual bacteria help balance the immune system in mice

Oct 15, 2009

Medical researchers have long suspected that obscure bacteria living within the intestinal tract may help keep the human immune system in balance. An international collaboration co-led by scientists at NYU ...

Study links 'hygiene hypothesis' to diabetes prevention

Oct 06, 2008

A research study funded by JDRF suggests that a common intestinal bacteria may provide some protection from developing type 1 diabetes. The findings provide an important step towards understanding how and why type 1 diabetes ...

Bugs in the gut trigger production of important immune cells

Oct 15, 2008

A new study reveals that specific types of bacteria in the intestine trigger the generation of pro-inflammatory immune cells, a finding that could eventually lead to novel treatments for inflammatory bowel disease and other ...

New 'suicide' molecule halts rheumatoid arthritis

Jan 28, 2010

A researcher from Northwestern University Feinberg School of Medicine has invented a novel way to halt and even reverse rheumatoid arthritis. He developed an imitation of a suicide molecule that floats undetected into overactive ...

Rheumatoid arthritis breakthrough

Nov 12, 2008

Rheumatoid arthritis is a painful, inflammatory type of arthritis that occurs when the body's immune system attacks itself. A new paper, published in this week's issue of PLoS Biology, reports a breakthrough in the unders ...

Recommended for you

Diet affects men's and women's gut microbes differently

12 hours ago

The microbes living in the guts of males and females react differently to diet, even when the diets are identical, according to a study by scientists from The University of Texas at Austin and six other institutions published ...

Researchers explore what happens when heart cells fail

14 hours ago

Through a grant from the United States-Israel Binational Science Foundation, Biomedical Engineering Associate Professor Naomi Chesler will embark upon a new collaborative research project to better understand ...

Stem cells from nerves form teeth

16 hours ago

Researchers at Karolinska Institutet in Sweden have discovered that stem cells inside the soft tissues of the tooth come from an unexpected source, namely nerves. These findings are now being published in the journal Nature and co ...

User comments : 1

Adjust slider to filter visible comments by rank

Display comments: newest first

barbara_allan
not rated yet Aug 12, 2010
It has been known for years that certain strains of mice prone to arthritis would not develop arthritis while their digestive tracts were bacteria-free, but would develop arthritis once bacteria were introduced. Is the new knowledge here that it only takes a single strain? Barbara Allan, author of the book Conquering Arthritis http://www.Conque...cles.htm