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.
Highlights
The aetiology of inflammatory bowel disease (IBD) is complex and not fully understood, yet
T. suis ova (TSO) treated animals maintained the constant weight gain observed in age-matched healthy controls (Fig. 1B, Supplementary Figure 1) that there was a significant difference in weight change between the TSO dextran sodium sulphate (DSS) and the DSS group on day 9 and 10 after start of DSS administration
TSO treatment delayed the onset of symptoms and reduced the disease severity significantly (DAI at day 9: 0.7 ± 0.2, P < 0.05 in comparison to the vehicle treated rabbits (Veh)-DSS group)
Summary
The aetiology of inflammatory bowel disease (IBD) is complex and not fully understood, yet. Different nematode species have been shown to suppress inflammation in mouse models of experimental colitis, mainly through the action of their excretory secretory (ES) products[5]. Mice previously infected with Trichuris muris recovered faster from DSS colitis and showed an increased regeneration of the mucosa suggesting that the protective effect of intestinal nematodes can persist after their clearance from the intestine[13]. Besides their immunomodulatory role, intestinal nematodes might positively affect the dysbiosis observed during intestinal inflammation. The current view is that T. suis larvae hatch and transiently colonize the human intestine for some weeks without reaching sexual maturity[19]
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