Tuftsin-Phosphorylcholine maintains normal gut microbiota in collagen induced arthritic mice

Rheumatoid arthritis (RA) is a chronic autoinflammation of the joints, with a prevalence of about 1% in Western populations. Evidence in recent years has linked RA to changes in the gut microbiota (dysbiosis). Interestingly, helminths have been shown to have therapeutic activity in RA. Specifically, a glycoprotein containing phosphorylcholine (PC) extracted from helminths was found to have immunomodulatory activity. We have previously developed a novel chimeric compound composed of tuftsin and PC (TPC) that attenuates the joint destruction in mice with collagen-induced arthritis (CIA). Here, we address the interrelationship between TPC immunomodulatory activity and the gut microbiota in CIA mice. Preventive therapy with TPC in mice with arthritis maintained a healthy arthritis score as well as a steady gut microbial environment, similar to that of healthy controls, in comparison to CIA mice with severe disease. The differences in microbial composition between healthy and PBS-treated CIA mice were significantly distinct, enabling classifying test samples by machine learning according to levels of relatively few bacterial species. Using these bacterial biomarkers, all TPC-treated CIA mice were classified as healthy. Thus, we describe a clear correlation between TPC treatment, healthy gut microbial communities, and prevention of arthritis. This is the first study to demonstrate the immunomodulatory effect of helminths derivatives in autoimmune diseases and the link to the gut microbiota.