Abstract
BackgroundEggs of the porcine whipworm Trichuris suis are currently explored in human clinical trials as a treatment of immune-mediated diseases. In this context, only the infective, embryonated eggs, constitute the Active Pharmaceutical Ingredient (API). The rodent whipworm, Trichuris muris is commonly used as a laboratory model to study Trichuris biology. The embryonated eggs (containing a fully developed larva) are biologically active and will invade the large intestinal mucosa of the host. This study aims to assess the in vitro hatching of T. muris and T. suis eggs in various bacterial cultures as a measure for their biological activity.MethodsEggs of T. muris and T. suis were incubated with Escherichia coli strain (BL-21) at three concentrations in a slightly modified in vitro egg hatching assay previously developed for T. muris. Additionally, E. coli strains (M15, SG13009, PMC103, JM109, TUNER, DH5alpha, TOP10) and five Gram-positive bacteria (Enterococcus caccae, Streptococcus hyointestinalis, Lactobacillus amylovorus, L. murinus, and L. reuteri) were tested as a hatching stimulus for T. muris and T. suis eggs.ResultsWhereas T. muris eggs hatched, T. suis did not, even when exposed to different concentrations and strains of E. coli after 4 and 24-hour incubation. When incubated with Gram-positive bacteria, only T. muris eggs showed noticeable hatching after 20 h, although with high variability.ConclusionsThe observed difference in hatching of T. muris and T. suis eggs incubated with selected bacteria, indicate significant biological differences which may reflect specific adaptation to different host-specific gut microbiota.
Highlights
Eggs of the porcine whipworm Trichuris suis are currently explored in human clinical trials as a treatment of immune-mediated diseases
The observed difference in hatching of T. muris and T. suis eggs incubated with selected bacteria, indicate significant biological differences which may reflect specific adaptation to different host-specific gut microbiota
After 4 h incubation, the two lowest concentrations of E. coli (BL-21) tested (5×108 and 10×108 bacteria/ml) resulted in significantly higher T. muris egg hatching than a concentration of 20×108 bacteria/ml (F2,9 = 54.20, p < 0.0001; Tukey’s post hoc test p < 0.0001)
Summary
Eggs of the porcine whipworm Trichuris suis are currently explored in human clinical trials as a treatment of immune-mediated diseases In this context, only the infective, embryonated eggs, constitute the Active Pharmaceutical Ingredient (API). The embryonated eggs of T. suis (TSO) represent a raw material of the Active Pharmaceutical Ingredient (API) in a medicinal product, which is currently being explored as a treatment for patients with immune-mediated diseases. Such helminthic therapy is founded on the hygiene hypothesis [4] or more broadly, the ‘Old friends’ hypothesis [5, 6]. Description of eggs based solely on their morphological development and appearance of larvae inside does not necessarily correlate with the egg hatchability, as larvae may degenerate over an extended period of storage
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