Synthetic food pigment sunset yellow potentiates food allergy via immune dysregulation and intestinal barrier dysfunction

Emerging evidence from clinical and experimental studies has suggested potential associations between artificial food pigments like Sunset Yellow (SY) and allergic reactions, though their mechanistic contributions remain unclear. This study investigated the immunological and epithelial effects of the synthetic pigment SY using a translational approach integrating mouse model assays. In the in vivo model, SY co-administration significantly exacerbated allergic responses, manifesting as enhanced weight loss, diarrhea, and elevated levels of histamine, MCP-1, and OVA-specific immunoglobulins (IgE and IgG). SY exposure promoted pronounced Th2 polarization, characterized by increased IL-4, IL-5, and IL-13 production alongside suppressed IL-2 levels, while maintaining comparably low levels of IFN-γ, TGF-β, and IL-10. Histopathological analyses revealed severe intestinal barrier damage and epithelial disruption. Complementary in vitro studies demonstrated that SY enhanced IL-1β secretion and subsequently downregulated tight junction proteins (ZO-1, Claudin-1). Mechanistically, SY was associated with activation of the MEKK1/IKK/NF-κB signaling pathway, establishing a self-amplifying inflammatory cycle that compromises epithelial integrity. These findings elucidate a multifaceted mechanism by which synthetic colorants may exacerbate allergic inflammation, underscoring the need to reconsider their safety assessment in food regulatory frameworks.