Parasite immunomodulation in autoimmune disease: focus on multiple sclerosis

Edwards, Laura; Constantinescu, Cris S.

doi:10.1586/eci.09.39

Cited by 8 publications

(3 citation statements)

References 27 publications

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“…On the other hand, with a few exceptions, multicellular organisms residing in the GI tract, such as parasitic worms (=helminths) are mostly considered detrimental to human health, as they can subtract nutrients, damage host tissues and release toxic waste products 14 – 16 . Nonetheless, in the developing world, infections by parasitic helminths have been associated with a low incidence of allergic and autoimmune diseases, as encompassed by the ‘hygiene hypothesis’ 17 , 18 ; this observation has led to the ‘curative’ properties of a range of GI helminths being investigated in a range of clinical trials aimed to develop novel therapeutics against selected chronic inflammatory disorders, such as ulcerative colitis 19 , 20 , Crohn’s disease 21 – 24 , coeliac disease 25 , 26 and MS 27 – 31 . Whilst preliminary results from a number of such trials are promising, a thorough understanding of the mechanisms that determine the anti-inflammatory properties of these helminths is necessary to assist the development of new effective therapeutics against these disorders.…”

Section: Introductionmentioning

confidence: 99%

A comprehensive analysis of the faecal microbiome and metabolome of Strongyloides stercoralis infected volunteers from a non-endemic area

Jenkins

Formenti

Castro

et al. 2018

Sci Rep

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Data from recent studies support the hypothesis that infections by human gastrointestinal (GI) helminths impact, directly and/or indirectly, on the composition of the host gut microbial flora. However, to the best of our knowledge, these studies have been conducted in helminth-endemic areas with multi-helminth infections and/or in volunteers with underlying gut disorders. Therefore, in this study, we explore the impact of natural mono-infections by the human parasite Strongyloides stercoralis on the faecal microbiota and metabolic profiles of a cohort of human volunteers from a non-endemic area of northern Italy (S+), pre- and post-anthelmintic treatment, and compare the findings with data obtained from a cohort of uninfected controls from the same geographical area (S−). Analyses of bacterial 16S rRNA high-throughput sequencing data revealed increased microbial alpha diversity and decreased beta diversity in the faecal microbial profiles of S+ subjects compared to S−. Furthermore, significant differences in the abundance of several bacterial taxa were observed between samples from S+ and S− subjects, and between S+ samples collected pre- and post-anthelmintic treatment. Faecal metabolite analysis detected marked increases in the abundance of selected amino acids in S+ subjects, and of short chain fatty acids in S− subjects. Overall, our work adds valuable knowledge to current understanding of parasite-microbiota associations and will assist future mechanistic studies aimed to unravel the causality of these relationships.

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Section: Introductionmentioning

confidence: 99%

A comprehensive analysis of the faecal microbiome and metabolome of Strongyloides stercoralis infected volunteers from a non-endemic area

Jenkins

Formenti

Castro

et al. 2018

Sci Rep

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“…Second, due to its unique life cycle, this helminth is safe for humans because it cannot establish infection through eggs (29). Third, considering the ethical limitations associated with the risk of helminthic infections in conducting clinical trials on humans (30), if the worm is to be considered a novel anti-colitic therapy, it can also be readily eradicated by administration of praziquantel at a patient's request.…”

Section: Discussionmentioning

confidence: 99%

Could Dicrocoelium dendriticum eggs play a potential immunotherapeutic role experimental colitis?

Mighani,

Eilakinezhad,

Esmaeili

et al. 2023

Preprint

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Inflammatory bowel disease (IBD) significantly diminishes an individual’s quality of life and elevates the likelihood of colorectal cancer. Recent clinical and experimental findings suggest that infection with parasitic helminths can exert a suppressive influence on the development of certain inflammatory conditions. The objective of this study was to evaluate the immunoregulatory impact of Dicrocoelium eggs on experimentally induced colitis using dextran sulfate sodium (DSS) in C57BL/6 mice. C57BL/6 mice were given 3.5% DSS orally daily for 7 days to induce colitis. During this period, the mice were treated with the Dicrosoeliumeggs intraperitoneally. Colitis intensity was investigated by assessing parameters such as body weight, stool consistency or bleeding, disease activity index (DAI), colon lengths, macroscopic scores, histopathological findings, colon gene expression levels, and serum cytokine levels. Our results indicated that the administration of Dicrocoelium eggs significantly led to reduction of severity of colitis and disease index. The histopathological scores improved, which were associated with the down-regulation of IFN-γ and up-regulation of IL-4 expression. Our results imply the therapeutic potential of Dicrosoelium eggs in treating colitis. Immunotherapy involving Dicrosoelium eggs primarily induces a Th2 response and modulates IFN-Y, contributing to the reduction of inflammation in colitis. Therefore, it can be considered a promising therapeutic approach to alleviate inflammation in inflammatory bowel disease (IBD).

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“…In fact, it has been proposed that, in order for the human immune system to operate optimally, the presence of helminth induced immunoregulatory networks are required [ 38 ]. Accordingly, in populations where parasitic infections are no longer endemic, there is an increased likelihood of inappropriate immune responsiveness to autoantigens, and the concomitant development of autoimmune/inflammatory diseases, such as MS. Consequently, many have asked the question of whether helminths should be regarded as beneficial commensals and whether the re-introduction of these old friends may be therapeutic in MS [ 7 , 39 , 40 , 41 , 42 , 43 ].…”

Section: Should We Reunite With Our Old Friends the Helminth Parasmentioning

confidence: 99%

Novel Therapeutics for Multiple Sclerosis Designed by Parasitic Worms

Dixit

Tanaka

Greer

et al. 2017

IJMS

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The evolutionary response to endemic infections with parasitic worms (helminth) was the development of a distinct regulatory immune profile arising from the need to encapsulate the helminths while simultaneously repairing tissue damage. According to the old friend’s hypothesis, the diminished exposure to these parasites in the developed world has resulted in a dysregulated immune response that contributes to the increased incidence of immune mediated diseases such as Multiple Sclerosis (MS). Indeed, the global distribution of MS shows an inverse correlation to the prevalence of helminth infection. On this basis, the possibility of treating MS with helminth infection has been explored in animal models and phase 1 and 2 human clinical trials. However, the possibility also exists that the individual immune modulatory molecules secreted by helminth parasites may offer a more defined therapeutic strategy.

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Parasite immunomodulation in autoimmune disease: focus on multiple sclerosis

Cited by 8 publications

References 27 publications

A comprehensive analysis of the faecal microbiome and metabolome of Strongyloides stercoralis infected volunteers from a non-endemic area

A comprehensive analysis of the faecal microbiome and metabolome of Strongyloides stercoralis infected volunteers from a non-endemic area

Could Dicrocoelium dendriticum eggs play a potential immunotherapeutic role experimental colitis?

Novel Therapeutics for Multiple Sclerosis Designed by Parasitic Worms

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