Mechanisms linking the bacterial breakdown of dietary tryptophan to the development of arthritis have been identified, according to a recent study published by Seymour et al in The Journal of Clinical Investigation. Previous studies have determined that there may be a correlation between altered tryptophan catabolism and inflammatory diseases such as rheumatoid arthritis and spondyloarthritis through the production of indole. Researchers used a mouse model involving collagen-induced arthritis to identify arthritis-related alterations in tryptophan metabolism. After mice on a low-tryptophan diet received indole supplementation, they found increased serum interleukin-6, tumor necrosis factor, and interleukin-1 beta levels; splenic retinoic acid–related orphan receptor gamma t–positive CD4-positive T cell and ex vivo collagen-stimulated interleukin-17 production; and anticollagen antibody isotype switching and glycosylation corresponding with heightened complement fixation. The researchers stressed that the presence of indole led to the development of more inflammatory, autoreactive T cells, the reduction of regulatory T cells, and the subsequent production of pathogenic antibodies. However, interleukin-23 neutralization effectively reduced disease severity in mice with collagen-induced arthritis and indole supplementation. Further, when human colonic lymphocytes were exposed to indole, the researchers noted increased expression of genes involved in interleukin-17 signaling and plasma cell activation. They hypothesized that inhibiting indole generation may be an effective treatment strategy for patients with arthritis.