"This is the first study to date that uses gut microbiome data to predict clinical improvement in rheumatoid arthritis disease activity independent of the initial measurement of their condition or prior treatment," says Jaeyun Sung, Ph.D., a computational biologist within Mayo Clinic's Center for Individualized Medicine and co-senior author of the study.
Rheumatoid arthritis is a chronic disorder characterised by joint inflammation and pain that can eventually lead to bone and cartilage erosion, joint deformity and loss in mobility.
During the past decade, the role of the gut microbiome in RA pathogenesis has been demonstrated by several experimental studies. Yet, the association of the gut microbiome with minimum clinically important improvement (MCII) in disease activity in RA patients has yet to be closely examined. The MCII represents the minimal meaningful change (reduction) in quantitative disease activity, and is relevant to patients in terms of improvement in disease symptoms and associated clinical parameters - it is therefore frequently used in clinical settings to evaluate the initial response to treatments.
For the study, researchers performed shotgun metagenomic sequencing on stool samples from 32 patients with rheumatoid arthritis at two separate clinical visits (approximately 6–12 months apart). First, they examined the association of gut microbiome with MCII in RA disease activity. Next, they examined microbiome properties (alpha- and beta-diversity, microbial taxa, and biochemical pathways) that differentiate patients who eventually showed clinical improvement from those who did not.
Afterwards, they identified taxonomic and functional features whose magnitude of and/or direction of change (from baseline to follow-up) varied differently between the two patient groups.
"By looking at patients' baseline gut microbiome profiles, we observed significantly different microbiome traits between patients who eventually showed improvement and those who did not," says John M. Davis III, M.D., a clinical rheumatologist at Mayo Clinic and co-senior author of the study.
Dr. Sung adds: "What was surprising is that our data suggest that depending on the eventual clinical outcome, gut microbiomes not only start at different ecological states, but also grow and develop differently."
Next, by using deep-learning artificial intelligence (AI), the investigators examined if they could predict whether a patient would achieve clinical improvement. Overall, the predictive performance resulted in 90% accuracy, thereby showcasing the proof of concept that the integration of gut microbiome and AI technology could theoretically be an avenue to predict disease course in rheumatoid arthritis.
The researchers note a number of limitations to the study, including the small sample size, lack of geographical/cultural diversity in the sample, variability of timings for follow-up clinic visits, and the small number of follow up time-points.
Path toward treatment
Dr Davis explains: "With further development, such prognostic biomarkers could identify patients who will achieve early clinical improvement with a given therapy, thereby sparing them the expense and risk of other therapies that are less likely to be effective.
"Conversely, such tools can detect patients whose disease symptoms are less likely to improve, and perhaps allow clinicians to target and monitor them more closely. Much is left to be done, but we're on the right path toward advancing our understanding of this disease in order to individualize medicine for patients with rheumatoid arthritis."
The study is the second recent RA investigation by Drs. Sung and Davis. Together, they are on a path toward developing a suite of new data-driven tools to aid in early detection, diagnosis, prognosis and treatment in rheumatoid arthritis. As such, the researchers plan to explore ways to translate their findings into new biomarkers and therapies.
"Ultimately, our study reveals that modifying the gut microbiome to enhance clinical outcome may hold promise as a future treatment for rheumatoid arthritis," Dr. Sung says. "This could revolutionize how we deliver care to our patients."
Source: Genome Medicine
Gupta. V. K., et al
"Gut microbial determinants of clinically important improvement in patients with rheumatoid arthritis"