Signals from the gut could transform rheumatoid arthritis treatment

Bacteria associated with inflammation is found in the gut in higher amounts roughly ten months before patients develop clinical rheumatoid arthritis, a longitudinal study by Leeds researchers has found.

Affecting more than half a million people in the UK, rheumatoid arthritis is a chronic disease that causes swelling, pain and stiffness in the joints because the immune system is mistakenly attacking the body's healthy cells.

Previous research has linked rheumatoid arthritis to the gut microbiome, which is the ecosystem of microbes in your intestines. But this new study, published today in the Annals of the Rheumatic Diseases, reveals a potential intervention point.

Lead researcher Dr Christopher Rooney, NIHR Academic Clinical Lecturer at the University of Leeds and Leeds Teaching Hospitals NHS Trust, said: "Patients at risk of rheumatoid arthritis are already experiencing symptoms such as fatigue and joint pain, and they may know someone in their family who has developed the disease. As there is no known cure, at-risk patients often feel a sense of hopelessness, or even avoid getting tested.

"This new research might give us a major opportunity to act sooner to prevent rheumatoid arthritis."

Major opportunity for treatment

Funded by Versus Arthritis, the longitudinal study was conducted on 19 patients at risk of rheumatoid arthritis, with samples taken five times during a 15-month period.

Five of these patients progressed to clinical arthritis, and the research showed they had gut instability with higher amounts of bacteria including Prevotella, which is associated with rheumatoid arthritis, about ten months before progression. The remaining 14, whose disease didn't progress, had largely stable amounts of bacteria in their gut.

Potential treatments that the researchers want to test at the ten-month window include changes to diet like eating more fibre, taking prebiotics or probiotics, and improving dental hygiene to keep harmful bacteria from periodontal disease away from the gut.

The exact relationship between gut inflammation and rheumatoid arthritis development remains unclear. In a small number of patients within the study, the gut changes occurred before there were any changes to the joints observed by a rheumatologist, but more research is needed to determine whether these influence each other.

Although bacteria is associated with rheumatoid arthritis, the researchers want to make it clear that there is no evidence this is contagious.

Lucy Donaldson, director for research and health intelligence at Versus Arthritis, said: "At Versus Arthritis, we welcome the findings of this study which could give the clinicians of the future a crucial window of opportunity to delay -- or even prevent -- the onset of rheumatoid arthritis. This success is testament to the dedication of UK researchers who are working to personalise treatment and prevent chronic conditions that have significant impacts on a person's ability to work, raise families and live independently."

Years in the making

The research was carried out in collaboration with the National Institute for Health Research Leeds Biomedical Research Centre, under the research themes of Antimicrobial Resistance and Infection and Musculoskeletal Disease.

Leeds Teaching Hospitals NHS Trust, Versus Arthritis and Leeds Hospitals Charity were also partners on the project. Patients at Chapel Allerton Hospital helped to design the research to make stool sampling easier for participants.

The study initially took data from 124 individuals who had high levels of CCP+, an antibody that attacks healthy cells in the blood, which indicates risk of developing rheumatoid arthritis. The researchers compared their samples to 22 healthy individuals and seven people who had a new rheumatoid arthritis diagnosis.

The findings from this larger group showed that the gut microbiome was less diverse in the at-risk group, compared to the healthy control group.

The longitudinal study, which took samples from 19 patients over 15 months, revealed the changes in bacteria at ten months before progression to rheumatoid arthritis.

The Leeds research team will now carry out an analysis of treatments that have already been trialed, to inform future testing of treatments at this potential ten-month intervention point.