Study links intestinal bacteria to rheumatoid arthritis

Researchers have linked a species of intestinal bacteria known as Prevotella copri to the onset of rheumatoid arthritis, the first demonstration in humans that the chronic inflammatory joint disease may be mediated in part by specific intestinal bacteria. The new findings by laboratory scientists and clinical researchers in rheumatology at NYU School of Medicine add to the growing evidence that the trillions of microbes in our body play an important role in regulating our health.

Using sophisticated DNA analysis to compare gut bacteria from fecal 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 genera Bacteroides.

"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, whose basic science laboratory at NYU School of Medicine's Skirball Institute of Biomolecular Medicine collaborated with clinical investigators led by Steven Abramson, MD, senior vice president and vice dean for education, faculty, and academic affairs; the Frederick H. King Professor of Internal Medicine; chair of the Department of Medicine; and professor of medicine and pathology at NYU School of Medicine.

"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 case."

The new findings, reported today 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.