Gut microbiome changes linked to onset of rheumatoid arthritis among at-risk individuals

Researchers observed the most significant gut microbiome instability in individuals who developed arthritis within 10 months of diagnosis, while those diagnosed 10-15 months later had a more stable profile. 

Study: Dynamics of the gut microbiome in individuals at risk of rheumatoid arthritis: a cross-sectional and longitudinal observational study. Image Credit: Alpha Tauri 3D Graphics/Shutterstock.com
Study: Dynamics of the gut microbiome in individuals at risk of rheumatoid arthritis: a cross-sectional and longitudinal observational study. Image Credit: Alpha Tauri 3D Graphics/Shutterstock.com

In a recent study published in the journal Annals of the Rheumatic Diseases, researchers from the United Kingdom explored gut microbiome changes in individuals at high risk for rheumatoid arthritis. By comparing gut bacteria profiles between individuals who eventually developed rheumatoid arthritis and those who did not, the researchers aimed to identify the microbial indicators that could signal early disease development.

Background

Rheumatoid arthritis is a chronic autoimmune disease that affects mainly the joints and sometimes other organs. Though its exact cause remains unclear, the onset of rheumatoid arthritis is believed to involve immune responses triggered by environmental and genetic factors. Studies have found that antibodies targeting proteins modified in specific ways often appear before symptoms, hinting at early immune activation preceding the disease.

Furthermore, smoking and gum disease are associated with rheumatoid arthritis, further suggesting that localized inflammation at mucosal sites, like the lungs or mouth, might initiate disease-related immune responses. Evidence from various studies also points to the gut microbiome’s potential role in the development of rheumatoid arthritis. While certain bacterial groups, such as Prevotella species, have been linked to rheumatoid arthritis, the findings from various studies about these microbial associations have been conflicting.

About the study

The present study examined gut microbial changes in people at risk for rheumatoid arthritis, focusing on the diversity and stability of gut bacteria over time to identify consistent microbial signatures associated with disease progression. The researchers used a combination of cross-sectional and longitudinal designs to analyze gut microbiome changes in individuals at risk for rheumatoid arthritis.

The participants included individuals with anti-cyclic citrullinated peptide (CCP) antibodies, which is a marker of rheumatoid arthritis risk. The study also included participants who had musculoskeletal pain without clinical arthritis, patients who were recently diagnosed with rheumatoid arthritis, and healthy controls. The researchers recruited individuals with diverse backgrounds and factors such as diet, lifestyle, and bowel habits.

Each participant provided stool samples, and data on demographic factors, antibody levels, and lifestyle factors were collected. The stool samples were analyzed for bacterial diversity and composition using two deoxyribonucleic acid (DNA) sequencing approaches. The 16S ribosomal ribonucleic acid (rRNA) amplicon sequencing targeted specific bacterial genes for broad taxonomic classification, while shotgun metagenomic sequencing was performed to obtain more detailed insights into bacterial strains and functional genes.

The researchers also performed diversity analysis to compare bacterial richness among participant groups, focusing on alpha diversity, which assesses the species diversity within samples, and beta diversity, which compares species diversities between samples. Various statistical analyses were then used to identify the bacterial taxa associated with the progression of rheumatoid arthritis.

Mixed-effects linear models were applied to capture changes in gut bacteria across time points for each participant while adjusting for demographic variables and antibody levels. Additionally, comparisons were also conducted to assess microbial stability over time, particularly within 10 months of the onset of rheumatoid arthritis. Furthermore, variability within the gut microbiome was analyzed to track shifts in bacterial composition before disease onset, identifying potential microbial markers linked to the development of rheumatoid arthritis.

Results

The study found that gut microbiome profiles differed significantly between individuals who eventually developed rheumatoid arthritis and those who did not. At baseline, the anti-CCP-positive individuals at risk for rheumatoid arthritis had lower gut microbiome diversity compared to healthy controls.

Furthermore, those who eventually developed rheumatoid arthritis showed greater changes in microbial diversity, and their gut microbiome was observed to become less stable within 10 months before the clinical symptoms of rheumatoid arthritis appeared.

The study revealed that specific strains within the Prevotellaceae family were more abundant in the individuals who eventually developed rheumatoid arthritis, while the other strains were less common, suggesting that Prevotella species played a complex role in rheumatoid arthritis. Individuals who eventually developed rheumatoid arthritis exhibited an accumulation of certain gut bacteria, including those from the Prevotellaceae family, within months of developing symptoms.

Furthermore, the findings highlighted an increase in the pathways related to amino acid and energy metabolism among the individuals who developed rheumatoid arthritis, indicating that metabolic shifts accompanied the microbiome changes associated with rheumatoid arthritis.

Moreover, the longitudinal analyses showed that the gut microbial diversity decreased progressively as individuals approached the onset of rheumatoid arthritis. The researchers conducted a stability analysis, which found that the microbiome became increasingly unstable and disordered in those close to developing rheumatoid arthritis, suggesting that these microbial shifts could be the early clinical signs of rheumatoid arthritis.

Conclusions

Overall, the results suggested that specific changes in gut microbiome composition and diversity, especially among anti-CCP-positive individuals, could be early indicators of increased risk of rheumatoid arthritis.

The observed microbial shifts could be considered potential markers for early rheumatoid arthritis. These findings also support the need for further exploration of gut bacteria as a tool for predicting and preventing rheumatoid arthritis.

Journal reference:
  • Rooney, C. M., Jeffery, I. B., Mankia, K., Wilcox, M. H., & Emery, P. (2024). Dynamics of the gut microbiome in individuals at risk of rheumatoid arthritis: a cross-sectional and longitudinal observational study. Annals of the Rheumatic Diseases, ard2024226362. doi:10.1136/ard2024226362, https://ard.bmj.com/content/early/2024/10/22/ard-2024-226362
Dr. Chinta Sidharthan

Written by

Dr. Chinta Sidharthan

Chinta Sidharthan is a writer based in Bangalore, India. Her academic background is in evolutionary biology and genetics, and she has extensive experience in scientific research, teaching, science writing, and herpetology. Chinta holds a Ph.D. in evolutionary biology from the Indian Institute of Science and is passionate about science education, writing, animals, wildlife, and conservation. For her doctoral research, she explored the origins and diversification of blindsnakes in India, as a part of which she did extensive fieldwork in the jungles of southern India. She has received the Canadian Governor General’s bronze medal and Bangalore University gold medal for academic excellence and published her research in high-impact journals.

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Comments

  1. AlanR Robb AlanR Robb Canada says:

    I first got RA at 50 in my right shoulder making Tai Chi uncomfortable. I'm now 86. Information was scarce and the doctor gave me 3 options, pain killers, physical therapy, grin and bare it. I tried all the different supplements to no avail. I read somewhere that heat may help, heat level and duration time were not included. I had an old heating pad . So I put it on my shoulder , set it on high and put a large towel on top to keep heat in.  Then spent about 3 hours watching TV movies. The next day my shoulder was red but arthritis was gone, but by the end of the day the redness was also gone.
    After that I started getting RA in most of my joints and experimented varying the two parameters. .There were stages of pain during the process.  First after many hours I found only the highest and second highest settings worked.
    The pain initially was was intense around the joint and after a while dropped to a lower level. When the pain went down to just warm I let the lingering for equivalent pain time again.
    Recently, because of COVID 19, I became interested in viruses and developed a simple treatment using heat to cause the virus demise. This led me back to how I stopped RA in which the temperatures were much higher but following the same rules with colds. This leads me to speculate that RA is virus related as the duration time for demise is similar.
    Also, our body's reaction of causing heat at offending infected areas, to me is a clue.
    Comparing the two situations of colds and AR I would say the arthritis viruses are more robust, first attacking the outside skin layer then slipping in through the synovial membrane to infect the joint.
    But what do I know . I'm a mechanical engineer. Alan Robb PEng retired, PhD

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
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