“The hypothesis,” said Dr. Steere, “is that with narrowed commensal diversity, certain organisms are able to expand, attach to and invade the gut mucosa, where they promote an exaggerated immune response, activating systemic inflammation in a way that contributes to joint disease.”3
A 2010 study using K/BxN TCR transgenic mice showed the importance of segmented filamentous bacteria (SFB) and Th17 responses in arthritis development.4 These mice are engineered to develop arthritis as a response to glucose-6-phosphate isomerase (GPI). The study showed the mice did not develop arthritis in a germ-free environment, “but the introduction of SFB in germ-free mice was sufficient to reinstate Th17 cells, leading to the production of autoantibodies and arthritis, and neutralization of IL-17 prevented arthritis,” he said.
Humans do not have SFB. Can other organisms in humans’ microbiota induce this type of response? The answer is yes, said Dr. Steere. In a 2017 study, IgA-coated E. coli bacteria promoted Th17-dependent inflammation in patients with Crohn’s disease-related spondyloarthritis (SpA).5 They determined the identity of bacterial strains by 16S rDNA sequencing, and showed that only one bacterial taxon, E. coli Shigella, was significantly different between the two patient groups. E. coli were more often coated with IgA in patients with Crohn’s SpA than in those with just Crohn’s disease.