Study reveals the gut microbiota’s ties to arthritis

The findings of a recent study may help identify targets for the prevention or treatment of rheumatoid arthritis and other inflammatory conditions.
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What is already known
Conditions such as inflammatory bowel disease have been linked to changes in gut bacteria, with patients showing alterations to their gut microbiotas. However, it’s unclear whether these links extend to other immune conditions such as rheumatoid arthritis, a chronic inflammatory disorder affecting the joints.

What this research adds
Researchers analyzed stool samples from 219 healthy adults and 221 people with rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis, and found that people with those inflammatory conditions showed alterations to their gut microbiotas. In particular, patients with more severe symptoms had increased levels of Ruminococcus gnavus and other pro-inflammatory bacteria compared with those with milder symptoms. In people with rheumatoid arthritis and linked conditions, the researchers also identified microbiota-driven pathways associated with inflammatory disease.

Conclusions
The findings may help identify targets for the prevention or treatment of rheumatoid arthritis and other inflammatory conditions.

Chronic inflammatory conditions affect nearly 20% of the global population, but not much is known about whether — and how — shifts in the gut microbiota are involved in some of these disorders. Now, researchers have found that specific changes in the microbial communities inhabiting the gut correlate with the severity of rheumatoid arthritis, a chronic inflammatory disorder affecting the joints, and related conditions.

The findings, published in Science Translational Medicine, may help identify targets for the prevention or treatment of these disorders. “Our study contributes to the growing body of evidence that the gut microbiome and inflammation throughout the body are tightly coupled,” the authors say.

Abnormal immune responses are responsible for many subtypes of arthritis, including rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. These immune responses can be triggered or sustained by interactions with gut microbial populations. But although conditions such as inflammatory bowel disease have been linked to changes in gut bacteria, it’s unclear whether these links extend to inflammatory arthritis.

To address this question, Kelsey Thompson at Harvard University in Boston, Massachusetts, and her colleagues analyzed stool samples from 219 healthy adults and 221 people with rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis.

Microbial shifts

From June 2015 to March 2020, the researchers recruited participants aged 20-93 from clinical centers across the United Kingdom. Compared with controls, people with inflammatory arthritis had an altered gut microbiota composition characterized by lower levels of beneficial bacteria such as Faecalibacterium prausnitzii and Roseburia intestinalis, and higher levels of Escherichia coli, Ruminococcus gnavus and other pro-inflammatory bacteria.

Patients with more severe symptoms had increased levels of Ruminococcus gnavus and other pro-inflammatory bacteria compared with those with milder symptoms, the researchers found.

Microbe types that were substantially more common in people with arthritis included Streptococcus species, which are normally found in the oral cavity but not in the gut. “Previous studies have found that the patients with [rheumatoid arthritis] were four times as likely to have poor dental health,” the researchers say. 

Disease pathways

Next, the researchers examined the functional implications of the microbiota alterations observed in people with arthritis. They identified several microbiota-driven pathways associated with inflammatory disease.

Some of these pathways impacted the gut’s ability to sequester iron and harvest vitamin B from food — changes that could have implications for disease. “Some of these alterations, such as those for B vitamin metabolism, could represent mechanisms for long-term prevention, risk reduction or treatment, as could microbial iron sequestration during arthritis-linked anemia,” the researchers say. 

Although it’s unclear whether the changes in gut bacteria are a cause or a consequence of alterations to the immune system, the findings may help inform future microbiota-based interventions, the authors say.