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June 6th, 2025
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University of Copenhagen
microbiology
biorxiv

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

Myhill, L. J.Open in Google Scholar•Jensen, P.Open in Google Scholar•Arora, P.Open in Google Scholar•Jensen, A. M.Open in Google Scholar•Zhu, L.Open in Google Scholar•Vedsted-Jakobsen, A.Open in Google Scholar•Thormar, E. A.Open in Google Scholar•von Munchow, A.Open in Google Scholar•Poojary, M. M.Open in Google Scholar•Lund, M. N.Open in Google Scholaret al.

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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