New research suggests that antibiotics may raise the risk of rheumatoid arthritis by altering the gut microbiota.

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New research suggests that antibiotics may put people at increased risk of rheumatoid arthritis.

About 1.3 million adults in the United States are living with rheumatoid arthritis (RA), an autoimmune condition that causes inflammation of the joints.

Researchers do not yet fully understand what drives RA, although they suspect a combination of genetic and environmental factors.

Some of the potential triggers of RA include hormonal changes and exposure to certain types of dust or fibers, as well as some viral or bacterial infections.

New research points to the use of antibiotics and the changes that such use may lead to in a person's gut microbiota as potential causes of RA.

Lindsay Hall, group leader at the Quadram Institute on the Norwich Research Park in the United Kingdom, is the last and corresponding author of the new study, which appears in the journal BMC Medicine.

Studying RA and antibiotics

Hall and team started from the observation that according to previous studies, using antibiotics, particularly in childhood, significantly raises the risk of developing infections and inflammatory bowel conditions.

More recent studies have suggested that antibiotics may also increase the risk of autoimmune conditions such as type 1 diabetes, autoimmune liver disease, and juvenile idiopathic arthritis.

Furthermore, the authors note, other studies in mice have shown that germ-free rodents do not go on to develop inflammatory arthritis, while human studies have found differences in the composition of the gut microbiota between people with and without the condition.

All of the above suggests that the microbiota plays an important role in the development of this inflammatory condition. So, Hall and team set out to "investigate the association between antibiotic prescriptions and the onset of RA using a large, U.K. based" dataset.

Antibiotics may raise RA risk by 60%

Sifting through data from the primary care Clinical Practice Research Datalink, the researchers found 22,677 cases of RA, matched them to more than 90,000 healthy controls, and clinically followed these people for an average of 10 years before they received a diagnosis of RA.

The analysis revealed that, on average, the odds of developing RA were 60% higher for people who had received antibiotics.

Specifically, those who had received a prescription for one course of antibiotics had 40% higher odds of developing RA, while those who took two courses had 66% higher odds. The odds were even higher among people who took three or four courses.

Those who had taken antibiotics more recently, meaning in the past 1–2 years, had 80% higher odds of developing RA. However, even prescriptions in the "distant past," meaning 5–10 years ago, carried an association with 48% higher odds.

The type of infection for which people had taken antibiotics also influenced the likelihood of developing RA.

Antibiotics for upper respiratory tract infections had a stronger association with cases of RA. However, the team did not identify this link in untreated cases, which suggests that it was the antibiotics that raised the risk.

"Antibiotic prescriptions are associated with a higher risk of RA," conclude the authors. "This may be due to microbiota disturbances or underlying infections driving risk," they say.

Study co-author Professor Christian Mallen, head of school for Primary, Community, and Social Care at Keele University, comments on the findings.

"This exciting work offers another glimpse into the complexity of understanding rheumatoid arthritis, opening the door for future work in this area," he says.

Lindsay Hall adds, "The more we learn about the complexity of the microbiome and how factors including antibiotics impact these diverse microbial ecosystems, the more insights we have into how this may alter key health outcomes."

"The challenge now is to unpick the mechanisms that link the microbes to different conditions, including RA, so that we can develop new therapeutics."