L J Myhill2; S Stolzenbach2; H Mejer2; T Hansen2; S Jakobsen2; P Nejsum1; S Thamsborg2; A Williams2;
1 Aarhus University, Denmark; 2 University of Copenhagen, Denmark
DiscussionFermentable dietary fibres, such as inulin, have been shown to influence mucosal immunity and gut health. In pigs, we have shown that dietary inulin modulated the characteristic Th2-immune response induced by the porcine whipworm, Trichuris suis, by synergistically up-regulating the expression of Th2 and mucosal barrier genes (e.g. IL13, TFF3), and down-regulating inflammatory genes (e.g. IFNG). We have subsequently used the murine whipworm infection model to further explore this novel diet-parasite interaction, where inoculation with either a low (20 eggs) or high (300 eggs) T. muris egg dose results in worm persistence or expulsion, respectively, in C57BL/6 mice.
Interestingly, dietary inulin enhanced worm numbers and size in both low- and high-dosed mice, and prevented worm expulsion in high-dosed mice typically resistant to infection. In these high-dosed mice, immune responses were markedly skewed towards a Th1-dominant state, as evidenced by increased numbers of T-bet expressing T-cells and IFNG and NOS2 caecal gene expression, and reduced mast cell numbers. Moreover, the inulin-induced persistence of T. muris altered gut microbiota profiles, with expansion of Proteobacteria and depletion of ‘healthy’ microbial phyla, such as Bacteroidetes and Actinobacteria observed. Conversely, in uninfected mice, inulin promoted the growth of Bacteroidetes, Actinobacteria and Verrucomicrobia (mainly Akkermansia muciniphila).
Our results indicate a profound effect of diet on T. muris infection and immune regulation in C57BL/6 mice. Elucidation of the inulin-mediated mechanisms responsible for T. muris persistence is still required, nevertheless these findings have clear implications for the use of diet in regulating helminth infection and host gut health.