Dietary non-starch polysaccharides impair immunity to enteric nematode infection

The influence of diet on immune function and resistance to enteric infection and disease is becoming well established. Highly processed, refined diets can lead to inflammation and dysbiosis, whilst health-promoting dietary components such as phytonutrients and fermentable fibres are thought to promote a healthy microbiome and balanced mucosal immunity. Chicory is a leafy green vegetable rich in fibres and bioactive compounds that may promote gut health. Unexpectedly, we show here we show that incorporation of chicory into semisynthetic AIN93G diets renders mice susceptible to infection with enteric helminths. Mice fed a high level of chicory leaves had a more diverse gut microbiota, but a diminished type2 immune response to infection with the small intestinal roundworm Heligomosomoides polygyrus. Furthermore, the chicory-supplemented diet significantly increased burdens of the large intestinal whipworm Trichuris muris, concomitant with a highly skewed type1 immune environment in caecal tissue. The chicory-supplemented diet was significantly enriched in non-starch polysaccharides, particularly uronic acids, and mice fed pectin-supplemented AIN93G diets had higher T. muris burdens and reduced IgE production and expression of genes involved in type2 immunity. Importantly, treatment of pectin-fed mice with exogenous IL25 restored type2 responses and was sufficient to allow T. muris expulsion. Collectively, our data suggest that increasing levels of fermentable, non-starch polysaccharides in refined diets compromises immunity to helminth infection in mice. This diet infection interaction may inform new strategies for manipulating the gut environment to promote resistance to enteric parasites.