Preventive Trichuris suis ova (TSO) treatment protects immunocompetent rabbits from DSS colitis but may be detrimental under conditions of immunosuppression

Abstract

Trichuris suis ova (TSO) have been tested for therapeutic application in inflammatory bowel diseases (IBD) yet understanding of the underlying mechanisms and safety in an immunocompromised host is limited due to lack of a suitable animal model. We used a recently established rabbit model of dextran sodium sulphate (DSS) induced colitis to study the efficacy, mechanisms and safety of TSO therapy in immunocompetent and immunosuppressed animals. TSO treatment prevented the DSS induced weight loss, delayed the onset of DSS induced symptoms by 2 days and significantly reduced the disease activity (DAI). TSO treatment protected caecal histology and prevented the colitis-associated loss in faecal microbiota diversity. Mainly the transcriptome of lamina propria mononuclear cells (LPMC) was affected by TSO treatment, showing dampened innate and adaptive inflammatory responses. The protective effect of TSO was lost in immunosuppressed rabbits, where TSO exacerbated colitis. Our data show that preventive TSO treatment ameliorates colitis severity in immunocompetent rabbits, modulates LPMC immune responses and reduces faecal dysbiosis. In contrast, the same TSO treatment exacerbates colitis in immunosuppressed animals. Our data provide further evidence for a therapeutic effect of TSO in IBD, yet caution is required with regard to TSO treatment in immunosuppressed patients.

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

“…It appears that such crosstalk has evolved to homeostatically maintain immune system function in health and disease 2 as GI helminths can induce regulatory responses to limit inflammation and promote intestinal barrier integrity while the intestinal bacteria play an essential role in training the immune system by impacting on stem and progenitor cells 13,14 . Consistent with the former, there is increasing evidence from animal models that the protection afforded by GI helminth infection, against inflammatory disorders associated with mucosal tissues like asthma 15 and inflammatory bowel disease 16,17 and coeliac disease 18,19 , involves modulation of the gut microbiota.…”

Immunotherapy for type 1 diabetes mellitus by adjuvant-free Schistosoma japonicum-egg tip-loaded asymmetric microneedle patch (STAMP)

“…During the last decades, studies on the mechanisms of immune regulation induced by parasitic worms may contribute to the development of new treatment strategies for inflammatory diseases such as inflammatory bowel disease, non-obese diabetes (NOD), collageninduced arthritis and so on [25,58]. A large amount of relevant studies involving experimental infection with helminth or treatment with parasite-derived components have proven to work wonders in practical applications of diverse animal experimental models or human experience, such as ingesting infectious Trichuris suis eggs for IBD, using filarial cystatin or products of Ancylostoma ceylanicum against collagen-induced arthritis, or taking hookworm protein for asthma therapy [59][60][61][62].…”

Safety of viable embryonated eggs of the whipworm Trichuris suis as a novel food pursuant to Regulation (EU) 2015/2283

“…Leonardi et al. () investigated the safety of T . suis in an immunocompetent and immunosuppressed host (using a rabbit model of dextran sodium sulfate‐induced colitis).…”

“…In addition, the Panel considered other animal studies available in the literature. Leonardi et al (2017) investigated the safety of T. suis in an immunocompetent and immunosuppressed host (using a rabbit model of dextran sodium sulfate-induced colitis). The authors showed that T. suis aggravate colitis in immunocompromised groups of rabbits receiving cyclosporine and methylprednisolone.…”