The parasitic worm product ES-62 normalises the gut microbiota bone marrow axis in inflammatory arthritis

Doonan, J., Tarafdar, A., Pineda, M. A. , Lumb, F. E., Crowe, J., Khan, A. M., Hoskisson, P. A., Harnett, M. M. and Harnett, W. (2019) The parasitic worm product ES-62 normalises the gut microbiota bone marrow axis in inflammatory arthritis. Nature Communications, 10, 1554. (doi: 10.1038/s41467-019-09361-0) (PMID:30952846) (PMCID:PMC6451002)

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Abstract

The human immune system has evolved in the context of our colonisation by bacteria, viruses, fungi and parasitic helminths. Reflecting this, the rapid eradication of pathogens appears to have resulted in reduced microbiome diversity and generation of chronically activated immune systems, presaging the recent rise of allergic, autoimmune and metabolic disorders. Certainly, gastrointestinal helminths can protect against gut and lung mucosa inflammatory conditions by modulating the microbiome and suppressing the chronic inflammation associated with dysbiosis. Here, we employ ES-62, an immunomodulator secreted by tissue-dwelling Acanthocheilonema viteae to show that helminth-modulation of the gut microbiome does not require live infection with gastrointestinal-based worms nor is protection restricted to mucosal diseases. Specifically, subcutaneous administration of this defined immunomodulator affords protection against joint disease in collagen-induced arthritis, a mouse model of rheumatoid arthritis, which is associated with normalisation of gut microbiota and prevention of loss of intestinal barrier integrity.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Khan, Aneesah and Harnett, Professor Margaret and Lumb, Miss Felicity and Crowe, Dr Jenny and Harnett, Professor William and Doonan, Dr James and Tarafdar, Ms Anuradha and Pineda, Dr Miguel
Authors: Doonan, J., Tarafdar, A., Pineda, M. A., Lumb, F. E., Crowe, J., Khan, A. M., Hoskisson, P. A., Harnett, M. M., and Harnett, W.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Nature Communications
Publisher:Nature Research
ISSN:2041-1723
ISSN (Online):2041-1723
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Nature Communications 10: 1554
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
703241MIMIC - Do parasitic worms and their secreted immunomodulators protect against musculosketal disease by impacting on the host microbiome?Margaret HarnettArthritis Research UK (ARTRESUK)21133III -IMMUNOLOGY