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.