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

Myhill, L. J.; Jensen, P.; Arora, P.; Jensen, A. M.; Zhu, L.; Vedsted-Jakobsen, A.; Thormar, E. A.; von Munchow, A.; Poojary, M. M.; Lund, M. N.; Thamsborg, S. M.; Limborg, M. T.; Jensen, B. A. H.; Williams, A. R.

doi:10.1101/2025.06.06.658267

bioRxiv · 10.1101/2025.06.06.658267

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

Myhill, L. J.·Jensen, P.·Arora, P.·Jensen, A. M.·Zhu, L.·Vedsted-Jakobsen, A.·Thormar, E. A.·von Munchow, A.·Poojary, M. M.·Lund, M. N.·Thamsborg, S. M.·Limborg, M. T.·Jensen, B. A. H.·Williams, A. R.

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Abstract

Dietary fibre regulates the microbiome and gut health but increases murine whipworm (Trichuris muris) infection through unclear mechanisms. We show that mice fed inulin-supplemented diets exhibit dysregulated innate antimicrobial defences and altered tryptophan metabolism during T. muris infection. 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 responses. 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.

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Myhill, L. J., Jensen, P., Arora, P., Jensen, A. M., Zhu, L., Vedsted-Jakobsen, A., Thormar, E. A., von Munchow, A., Poojary, M. M., Lund, M. N., Thamsborg, S. M., Limborg, M. T., Jensen, B. A. H., Williams, A. R.. 2025-06-06. Dietary fibre promotes chronic whipworm infection through direct and time-dependent modulation of innate immunity. https://doi.org/10.1101/2025.06.06.658267

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