Soybean-Derived Soluble Fiber Enhances Antimicrobial Proteins in the Mouse Small Intestine via a Tuft Cell-Group 2 Innate Lymphoid Cell Axis.

Water-soluble soybean fiber (WSSF) exerts health benefits beyond its fermentability, but its direct effects on epithelial-immune interactions remain unclear. We investigated whether WSSF regulates antimicrobial proteins (AMPs) in the small intestine and the underlying mechanisms. C57BL/6J and tuft cell-deficient Pou2f3-knockout mice were fed control or WSSF-supplemented diets, and gene and protein expression and cecal microbiota were analyzed. WSSF upregulated the epithelial AMPs SPRR2A, RELMβ, and ANG4 in the jejunum and ileum. Pharmacological inhibition of group 2 innate lymphoid cells (ILC2) or TRPM5 attenuated AMP induction and reduced IL-25, IL-13, tuft cell markers, and STAT6 phosphorylation. WSSF also failed to induce AMPs or type 2 immune markers in Pou2f3-knockout mice, indicating a requirement for tuft cells. Finally, WSSF altered cecal microbiota composition in a tuft cell-dependent manner. These findings identify WSSF as a soybean-derived fiber that strengthens epithelial innate defense via a TRPM5-tuft cell-ILC2 axis.