Rare diseases

Parasitic worm immunomodulator acts on microbiome to prevent arthritis


An immunomodulator product derived from parasitic worms acts on the microbiome to protect against arthritis, new research shows

Scientists in Scotland have been investigating how gastrointestinal helminths may protect against gut and lung mucosa inflammatory conditions by modulating the microbiome and suppressing the chronic inflammation associated with dysbiosis. Their work is based on the belief that the rise in autoimmune and allergic conditions in developed countries may be linked to loss of traditional commensal bacteria and GI helminths that evolved to reciprocally regulate the gut microbiome to homeostatically maintain immune system function.

Writing in Nature Communications they describe how they used  ES-62, an immunomodulator secreted by the helminth Acanthocheilonema viteae to show that modulation of the gut microbiome can be achieved without live infection with gastrointestinal-based worms.

Subcutaneous administration of ES-62 in mice protected them against joint disease in collagen-induced arthritis. And importantly, the protective effects correlated with normalisation of gut microbiota and prevention of loss of intestinal barrier integrity

The researchers said the findings supported the hypothesis that in gastrointestinal helminths could induce regulatory responses to limit inflammation and promote intestinal barrier integrity.

The immunomodulator ES-62  has previously been shown to prevent initiation and progression of allergic (asthma, contact dermatitis) and autoimmune (RA, SLE) inflammatory diseases in animal models, they noted.

The new research showed that arthritis in the joints was preceded by dysbiosis, intestinal inflammation and loss of GI barrier integrity. They therefore postulated that autoimmine conditions may be triggered by gut bacteria translocating to non-gut organs due to increased GI epithelial permeability to non-gut organs

This view was supported by Monash University researchers, who said in an accompanying commentary that the immunomodulator ES-62 may work by promoting gut bacteria that produce the short-chain fatty acid butyrate.

Butyrate has been reported to influence regulatory T-cell function, suppress osteoclastogenesis, and by protecting against pathological bone loss, to regulate bone mass.

“Notably, butyrate is a well-known modulator of gut barrier function and inflammation, providing a possible mechanism by which ES-62–microbiota interactions could additionally influence gut pathology,” wrote Dr Gillian Coakley (PhD) and Dr Nicola Harris (PhD) of the Monash Department of Immunology and Pathology, Monash University.

“Future studies aimed at generating an in-depth view of associations between helminths, the gut microbiome and disease (potentially in humans) could enable the development of novel and effective microbe-based and/or metabolite-based treatments for patients with RA,” they conclude.

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