The revolution of culture-independent, high-throughput microbial DNA sequencing, in parallel with the resurgence of interest in further understanding mucosal immunity, has greatly advanced our knowledge of the interplay between our commensual microbes and ourselves. Despite the relative novelty of the human microbiome as an area of study, a substantial body of evidence has accumulated addressing its potential involvement in the pathogenesis of rheumatic disease. This review article explores the available data in animal and human studies, focusing on the role of the intestinal microbiome in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and the spondyloarthritidies (SpA).
Taken together, the findings of the studies discussed in this article suggest that perturbations in the composition of the intestinal microbiota may be sufficient to trigger arthritis in a variety of murine experimental models of disease. However, potentially joint-protective (or joint-deleterious) properties might also depend on host genetic background and sex. For example, arthritis-susceptible mice show alterations in intestinal microbiota composition and increases in gut permeability when compared with arthritis-resistant controls.
Some interesting findings:
- Increases in Prevotella correlated with a reduction in reportedly beneficial microbes (i.e., Bactereoides) in patients with new-onset RA.
- Significant differences between the metagenomes of the cohorts exist and may be functionally relevant as predictors of treatment response. Levels of dihydrofolate reductase (DHFR) are high in metagenome samples rich in Bacteroides, potentially competing with host DHFR for methotrexate (MTX) binding and metabolism. If this is the case, an increase in DHFR-high microbiota in RA patients may help explain why only some RA patients respond adequately to oral MTX.
- P copri has the ability to dominate the intestinal microbiota, resulting in an increased sensitivity to Dextran sulfate sodium–induced colitis.
In sum, these findings reveal a potential role of the gut microbiome in the pathogenesis of RA. These findings remain correlative and do not represent evidence of causation, but nevertheless prompt further investigations in human disease.
Excerpted and adapted from:
Scher JU, Littman DR, Abramson SB. Review: Microbiome in inflammatory arthritis and human rheumatic diseases. Arthritis Rheumatol. 2016 Jan;68(1):35–45.