Tuftsin-Phosphorylcholine Maintains Normal Gut Microbiota in Collagen Induced Arthritic Mice

Abstract

Rheumatoid arthritis (RA) is characterized by 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-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 physiological arthritis score as well as a steady gut microbial environment, similar to that of healthy controls, in contrast to CIA mice with severe disease. The microbial composition differed significantly between healthy and phosphate-buffered saline-treated CIA mice, enabling classifying test samples by machine learning based on levels of a small number of 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 helminth derivatives in autoimmune diseases and the link to gut microbiota.

Alteration of the intestinal microbiome characterizes preclinical inflammatory arthritis in mice and its modulation attenuates established arthritis

“…Another study compared the microbiome of healthy non-immunized mice and mice with CIA. This study found that Clostridiales, Lachnospiraceae and Ruminoccocus gnavus were more abundant in the mice with established CIA compared to the healthy mice 45 . Interestingly, we found these taxa to be increased in the preclinical phase and before the onset of arthritis.…”

Microbiota‐Dependent Involvement of Th17 Cells in Murine Models of Inflammatory Arthritis

“…While several studies have demonstrated that experimental arthritis can be exacerbated by SFB , it is unclear whether these arthritogenic effects are due to Th17 cell induction or due to T follicular helper cell induction and autoantibody production . Microbiome perturbations occur during CIA, and the composition of the microbiota differs between both naive and arthritic CIA‐susceptible and ‐resistant mouse strains . Tuftsin phosphorylcholine, a natural glycoprotein with tolerogenic potential, attenuates the development of CIA and prevents dysbiosis in mice .…”

“…Microbiome perturbations occur during CIA, and the composition of the microbiota differs between both naive and arthritic CIA‐susceptible and ‐resistant mouse strains . Tuftsin phosphorylcholine, a natural glycoprotein with tolerogenic potential, attenuates the development of CIA and prevents dysbiosis in mice . Studies on microbiota‐dependent differentiation of Th17 cells in the K/BxN mouse model of arthritis have demonstrated that Th17 cell induction in SFB‐colonized mice occurs around weaning and precedes the onset of arthritis .…”

Helminth-Based Product and the Microbiome of Mice with Lupus

“…DNA was extracted from feces using the Power Soil DNA isolation kit (Mo Bio) according to the manufacturer's instructions, using a Beadbeater (BioSpec) for 2 min. Following DNA extraction, the bacterial 16S rRNA gene V4 variable region was amplified, purified, quantified, and sequenced using an Illumina MiSeq platform as previously described (34). Data analysis was performed using QIIME2 (35).…”