Rheumatoid arthritis associated with changes in the intestinal microbiome

About 374,000 Canadians today live with rheumatoid arthritis (RA), a chronic autoimmune disease that causes the immune system to mistakenly attack the walls of the joints in the hands and feet, causing inflammation and painful swelling. Its exact causes have not been established—it is known, however, that genetics, environmental factors, smoking and obesity can increase the risk of developing the disease—and to date there is no treatment. However, a recent study suggests the possibility of developing new strategies for early prevention.Researchers at the University of Leeds Institute of Medical Research in the U.K. report that certain changes in the gut microbiome may be linked to the development of rheumatoid arthritis. To reach these conclusions, Dr. Christopher Rooney's team recruited 153 participants—124 people at risk of developing RA, seven people recently diagnosed with the disease and 22 healthy controls—and followed changes in their gut microbiomes for more than 15 months.“People at risk of RA were defined by the presence of anti-cyclic citrullinated protein (anti-CCP) antibodies and new musculoskeletal symptoms without clinical synovitis,” said the study authors, whose paper was recently published in the journal Annals of the Rheumatic Diseases. These antibodies are a type of protein produced by the immune system, generally in response to inflammation.During the course of the study, 30 of the 124 participants at risk developed rheumatoid arthritis. Among these 30 people, the researchers noted that their microbial diversity was significantly reduced compared with that of healthy controls, particularly as regards levels of anti-CCP antibodies.“Longitudinal sampling revealed instability of the intestinal microbiome in progressors 10 months before the onset of RA, a phenomenon absent in non-progressors,” the study stated.These antibodies could therefore appear in the blood well before symptoms such as joint pain or stiffness. This is a warning sign that could enable doctors to identify people at risk, and to consider strategies likely to slow down or alter the progression of the disease even before it develops fully, say the researchers.This instability of the microbiome is marked in particular by the accumulation of the Prevotellaceae bacterial species. The Prevotella Copri strain in particular was found to be abundant in the intestinal microbiome of participants who had experienced progression of RA during the course of the study, as well as in those in the newly diagnosed group.“This microbial signature is consistent and correlated with traditional RA risk factors,” the study said. The inflammation associated with RA could therefore begin not in the joints, but in the intestine, the researchers suggest.The bacterial strain was not present in the microbiomes of participants in the healthy control group. These bacteria could therefore be involved in the progression of RA by “preparing” the immune system for the disease.“These results illustrate the dynamic nature of the gut microbiome, reflecting an individual's underlying risk profile and the transition from an at-risk situation to the development of clinical arthritis,” the authors concluded.In their view, this development of knowledge could “have a significant impact on approaches to prediction, prevention and personalised treatment strategies for RA, highlighting the need for further research into microbiome-based diagnostics and therapies.”

Rheumatoid arthritis associated with changes in the intestinal microbiome

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