Rheumatoid arthritis linked to changes in the gut microbiome in new study

For this study, researchers recruited 124 people at risk of developing rheumatoid arthritis, seven people who had recently received a diagnosis for the condition, and 22 healthy controls.

Scientists tracked changes in the gut microbiomes of all participants for over 15 months.

“Signals in the blood of [rheumatoid arthritis] patients suggest inflammation may start in sites outside of the joints, such as the gut,” Rooney explained.

“Previous research had shown those with established [rheumatoid arthritis] had a different microbiome when compared to people that do not have [rheumatoid arthritis]. We therefore asked the question: Do those at risk of [rheumatoid arthritis] also have a different microbiome and if so, when do those changes occur?”

– Christopher Rooney, MD, PhD

“The gut microbiome is in constant conversation with the immune system, and so inflammation at a local level can cascade through the immune system and cause system effects,” he added.

During the study, 30 of the 124 at-risk participants developed rheumatoid arthritis.

Of these 30 participants, researchers noticed their microbial diversity was significantly reduced when compared to that of the healthy controls, especially in an area known as alpha diversity, which was linked to levels of precursor anticyclic citrullinated protein (anti-CCP) antibodies.

Researchers found that participants with low anti-CCP antibody levels in their gut microbiome were comparable to that found in the healthy control group.

“Anti-CCP antibodies are a type of protein produced by the immune system, typically in response to inflammation,” Rooney said.

“In people who may develop [rheumatoid arthritis], these antibodies can appear in the blood long before any symptoms, like joint pain or stiffness, become noticeable. Essentially, the presence of anti-CCP antibodies acts as an early warning signal for [rheumatoid arthritis], helping doctors identify individuals at higher risk of developing the condition,” he explained.

“This finding is significant because it opens the door to earlier monitoring and allows us to study the disease before its onset,” Rooney continued. “Knowing that someone has these antibodies allows healthcare professionals to keep a closer eye on them and consider strategies that might slow down or alter the course of the disease, even before it fully develops.”

Rooney and his team also identified specific bacteria in the gut microbiome that may be involved with rheumatoid arthritis progression.

For example, scientists found that a specific strain of the bacteria species Prevotellaceae sp — (ASV2058) most likely the bacteria Prevotella copri — was plentiful in the microbiomes of participants who experienced rheumatoid arthritis progression during the study, as well as those in the newly diagnosed group, but was not seen in the microbiomes of those in the healthy control group.

Researchers also noticed an increase of another strain (ASV1867) of P. copri at the beginning of the study in the microbiomes of participants who progressed to rheumatoid arthritis, possibly suggesting certain strains of .P copri may play different roles in rheumatoid arthritis progression.

“These two strains exemplify how the underlying risk of a patient, for example their genetics, is linked to changes in the gut microbiome at [rheumatoid arthritis] progression,” Rooney told us.

“The significance of this finding lies in the idea that certain bacteria in our gut might play a role in ‘priming’ the immune system in ways that could eventually lead to [rheumatoid arthritis]. By identifying these strains, we gain a better understanding of how the gut microbiome might influence [rheumatoid arthritis] risk,” he noted.

Rooney said these findings may one day lead to new treatment options for rheumatoid arthritis.

“Our findings suggest that certain bacteria in the gut microbiome may be involved in triggering the immune changes that lead to rheumatoid arthritis,” he explained. “If we can confirm and better understand this connection, it could pave the way for new treatment approaches targeting the microbiome.”

“One potential strategy could be to develop therapies that specifically alter or ‘rebalance’ the gut microbiome, possibly through the use of probiotics, dietary interventions, or microbiome-based medications,” Rooney continued.

“By reducing or modifying the presence of bacteria associated with [rheumatoid arthritis], it may be possible to lower the risk of the disease progressing. While more research is needed, this line of inquiry holds promise for preventive and personalized treatments that could improve outcomes and quality of life for those susceptible to [rheumatoid arthritis].”

– Christopher Rooney, MD, PhD

“Our next steps involve studying how these specific bacteria influence immune activity in greater detail to confirm their role in rheumatoid arthritis development,” he added. “We will also explore interventions that could modify the gut microbiome in those at risk, such as targeted probiotics or dietary changes, aiming to understand if these approaches might prevent or delay disease onset.”