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; William Harnett

doi:10.1038/s41467-019-09361-0

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^*, William Harnett^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

50 Citations (Scopus)

6 Downloads (Pure)

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.

Original language	English
Article number	1554
Journal	Nature Communications
Volume	10
DOIs	https://doi.org/10.1038/s41467-019-09361-0
Publication status	Published - 5 Apr 2019
Externally published	Yes

Keywords

inflammation
microbiome
parasite biology
parasite infection

ASJC Scopus subject areas

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General Physics and Astronomy

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10.1038/s41467-019-09361-0

Doonan, J. et al (2019) The parasitic worm product ES-62 normalises the gut microbiota bone marrow axis in inflammatory arthritis
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Final published version, 2.31 MBLicence: CC BY

Cite this

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

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.",

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AU - Doonan, James

AU - Tarafdar, Anuradha

AU - Pineda, Miguel A.

AU - Lumb, Felicity E.

AU - Crowe, Jenny

AU - Khan, Aneesah M.

AU - Hoskisson, Paul A.

AU - Harnett, Margaret M.

AU - Harnett, William

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AB - 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.

KW - inflammation

KW - microbiome

KW - parasite biology

KW - parasite infection

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AN - SCOPUS:85063982406

SN - 2041-1723

VL - 10

JO - Nature Communications

JF - Nature Communications

M1 - 1554

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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