Dietary soy shapes murine microbiota to consolidate the mucosal IgA response through T follicular helper cells

Summary The commensal microbiota plays a crucial role in shaping mucosal immunity, particularly in the induction of T follicular helper (Tfh) cells and IgA production. Here, we demonstrate that dietary soy elicits a robust Tfh cell and IgA response in Peyer’s patches of weaning mice. Soy feeding promotes the expansion of two principal commensal bacterial species, Limosilactobacillus reuteri and Muribaculum intestinale . Mechanistically, L. reuteri provides cognate antigens for Tfh cell activation, while M. intestinale functions as an adjuvant by promoting IL-1β production from myeloid cells. The resulting IgA exhibits polyreactivity and enhances protection against Salmonella infection. These findings highlight the specific interplay among dietary components, intestinal microbiota, and mucosal immunity, thereby establishing a diet-microbe-immune axis that shapes host defense in early life. This axis represents a promising therapeutic target for developing novel strategies to enhance resistance to enteric pathogens. Graphical abstract Highlights Dietary soy promotes T follicular helper (Tfh) cell and IgA responses in the Peyer’s patches of weaning mice. Soy enhances the colonization of two key commensals , Limosilactobacillus reuteri and Muribaculum intestinale, in the small intestine. These two bacteria synergize to drive mucosal immunity: L. reuteri provides cognate antigens, while M. intestinale provides an adjuvant signal by promoting IL-1β production from myeloid cells. Soy-induced IgA is polyreactive and protects against Salmonella infection.