Dietary fibre promotes chronic whipworm infection through direct and time-dependent modulation of innate immunity

Dietary fibre regulates the microbiome and gut health but increases murine whipworm (Trichuris muris) infection through unclear mechanisms. We show that inulin-supplemented diets cause dysregulated innate antimicrobial defences despite acute T-cell immunity. Inulin intake altered tryptophan metabolism and aryl-hydrocarbon receptor activation. Inhibiting tryptophan catabolism or neutralizing IL-27 and IL-18 in inulin-fed mice restored infection resistance. Notably, inulin led to chronic infection even in microbiota-depleted mice. Removing inulin within a critical immune development window rapidly restored anti-helminth immunity, indicating direct, time-dependent modulation of mucosal immune response. Our findings reveal a previously unrecognized, direct influence of dietary fibre on mucosal immunity to parasitic infection, independent of the microbiome, highlighting the complex interplay between diet timing and host defence.