Dietary Sucralose Exacerbates Ovalbumin-Induced Food Allergy via Dendritic Cells Modulation: In Vitro and In Vivo Studies

Sucralose, a common zero-calorie sweetener, may increase food allergy (FAs) risk via immune modulation, although its mechanisms remain poorly understood. This study investigates how sucralose exacerbates allergic responses in mice that are OVA-sensitized through specific immunologic mechanisms. Sucralose exposure markedly aggravated allergic symptoms, including diarrhea, elevated serum IgE, MCP-1, and mast cell mediators, and preferentially enhanced Th2 responses without affecting Th1 or Treg cytokine pathways. At the cellular level, sucralose stimulated dendritic cells (DCs) activation, increasing expression of MHCII (OVA +5 mM vs OVA, +46.81%) and CD80/CD86 (OVA +5 mM vs OVA, +37.12%/12.29%), and promoting Th2 polarization via altered cytokine profiles. Importantly, sucralose activated the TLR4/MyD88/NF-κB pathways in DCs, boosting pro-inflammatory IL-6 and IL-1β releases, which amplified T cell activation and allergic inflammation. The findings indicated that sucralose potentiates the OVA-induced FA by activating DC-mediated TLR4 activation, thereby augmenting pro-inflammatory production and sustaining allergic responses. These findings highlighted the potential immunological risks associated with widespread sucralose consumption.