Intra-genus dysbiosis of Streptococcus in tonsillar microbiota is associated with host immune features in rheumatoid arthritis

Abstract

Abstract Background Palatine tonsils are mucosa-associated lymphoid organs that constantly engage in crosstalk with commensal microorganisms and the immune system. Focal infections at tonsils have been implicated in the pathogenesis of autoimmune diseases including rheumatoid arthritis (RA), but the underlying mechanisms through which tonsils contribute to host autoimmunity remain poorly defined. Results We identified a significant dysbiosis of tonsillar microbiota in RA patients, which was largely associated with disease activity. RA tonsillar microbiota was featured by an expansion of opportunistic pathogenic Streptococcus species including S. pyogenes, S. dysgalactiae and S. agalactiae, along with a contraction of numerous commensal Streptococcus members like S. salivarius. By defining a Streptococcus dysbiosis index, we found that RA patients, especially those without medication, were overrepresented in the Streptococcus dysbiotic set. Moreover, the intra-genus dysbiosis of Streptococcus in tonsillar microbiota was closely correlated with abnormal expression of circulating anti-streptolysin O, LPS-binding protein, soluble CD14, T helper 17 and natural killer cells. Finally, we demonstrated that the RA-deficient S. salivarius inhibited arthritis development and autoimmune responses. Conclusions Collectively, our study uncovers the functional link between host immune responses and tonsillar microbiota, and demonstrates that intra-genus dysbiosis of Streptococcus species contribute significantly to host autoimmunity.