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

James Doonan, Anuradha Tarafdar, Miguel A. Pineda, Felicity E. Lumb, Jenny Crowe, Aneesah M. Khan, Paul A. Hoskisson, Margaret M. Harnett () and William Harnett ()
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James Doonan: University of Strathclyde
Anuradha Tarafdar: University of Glasgow
Miguel A. Pineda: University of Glasgow
Felicity E. Lumb: University of Strathclyde
Jenny Crowe: University of Glasgow
Aneesah M. Khan: University of Glasgow
Paul A. Hoskisson: University of Strathclyde
Margaret M. Harnett: University of Glasgow
William Harnett: University of Strathclyde

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-09361-0

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