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

Hila Ben-Amram, Tomer Bashi, Nir Werbner, Hadar Neuman, Mati Fridkin, Miri Blank, Yehuda Shoenfeld, Omry Koren

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28 Scopus citations

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.

Original languageEnglish
Article number1222
JournalFrontiers in Microbiology
Volume8
Issue numberJUL
DOIs
StatePublished - 10 Jul 2017

Bibliographical note

Publisher Copyright:
© 2017 Ben-Amram, Bashi, Werbner, Neuman, Fridkin, Blank, Shoenfeld and Koren.

Funding

This study was supported by Morris Family Foundation, Los Angeles, CA, United States and TEVA Ltd., grant no. 147333 Israel. The work of OK is supported by the Marie Curie International Reintegration Grant (FP7-PEOPLE-2013-CIG-630956), the Ministry of Health, State of Israel (3-0000-10451), and the Alon fellowship.

FundersFunder number
Morris Family Foundation
TEVA Ltd.FP7-PEOPLE-2013-CIG-630956, 147333
University of California Institute for Mexico and the United States
Seventh Framework Programme630956
Ministry of Health, State of Israel3-0000-10451

    Keywords

    • Collagen-induced arthritis
    • Helminths
    • Microbiome
    • Rheumatoid arthritis
    • Tuftsin-phosphorylcholine

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