Inflammatory arthritis and the gut microbiome

Nearly 54 million adults in the U.S. are afflicted with various forms of arthritis. Rheumatic conditions are among the many chronic inflammatory diseases in which the microbiome has been implicated, but comprehensive, large-scale multi-omic evaluations conducted in patient cohorts with careful disease and environmental phenotyping are lacking. To characterize the community structure and metabolic processes driving gut microbiome involvement in arthritis, we investigated stool shotgun metagenomes from 273 adults diagnosed with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and other forms of arthritis, as well as 100 control individuals. We found that ~2% of gut taxonomic variability was explained by patient diagnosis, similar in magnitude to inflammatory bowel disease (IBD), which has been the focus of the considerably greater investigation. Similar findings were identified for gut microbial functional profiles, suggesting a tight coupling between perturbed microbial community structure and the metabolic functions they encode among patients with established arthropathy. After adjusting for age, gender, ethnicity, and other relevant clinical characteristics that may confound the relationship between arthropathy and the microbiome, we identified significant increases in several taxa characteristic of the oral cavity among patients with high rather than low circulating C-reactive protein, an established biomarker for systemic inflammation, including several species from Streptococcus and Ruminococcus genera. We are currently testing for strain-specific carriage of genetic elements implicated in the gut microbiome during arthritis subsets, as well as the ability of microbial elements to discriminate disease or predict response to treatment. Untargeted metabolomic profiles have also been generated for a subset of samples in order to link potentially causal microbial changes to mediating small molecules. Taken together, our efforts represent the first comprehensive investigation of gut microbial communities in a well-defined clinical cohort of individuals with inflammatory and non-inflammatory arthropathies.

Funding source: Versus Arthritis