Dietary pectin enhances intestinal antimicrobial protein expression via a tuft cell-ILC2-STAT6 signaling axis.

Dietary fibers are known to modulate intestinal physiology; however, the cellular mechanisms linking dietary fiber intake to epithelial immune responses remain incompletely understood. Here, we investigated the effects of pectin, a citrus-derived dietary fiber, on antimicrobial protein expression in the mouse small intestine. Pectin supplementation markedly upregulated the expression of antimicrobial proteins, including RELMβ, ANG4, SPRR2A, and REG3 family members, accompanied by enrichment of gene pathways related to host defense. These effects were associated with activation of type 2 immune responses, as evidenced by increased expression of interleukin (IL)-25 and IL-13, expansion of tuft cells, and enhanced STAT6 phosphorylation. Pharmacological inhibition of group 2 innate lymphoid cells (ILC2) suppressed pectin-induced antimicrobial protein expression, indicating a critical role of ILC2-mediated signaling. Furthermore, these responses were completely abolished in tuft cell-deficient Pou2f3-knockout mice, demonstrating that tuft cells are indispensable for pectin-induced immune activation. In addition to host responses, pectin altered intestinal microbiota composition in both tuft cell-dependent and -independent manners, including a reduction in Akkermansia abundance under fiber-rich conditions. Collectively, these findings reveal that pectin activates a tuft cell-ILC2-STAT6 signaling axis to enhance antimicrobial protein production and modulate host-microbiota interactions. This study provides new insight into how dietary fibers directly regulate intestinal epithelial immunity and barrier function.