Dietary soy shapes the microbiome to induce commensal-specific T follicular helper cells and IgA production

The commensal microbiota plays a crucial role in shaping mucosal immunity, particularly in the induction of T follicular helper (Tfh) cells and subsequent B cell 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 future strategies to enhance resistance to enteric pathogens.