Sialic Acid (Neu5Ac)-Driven Modulation of Intestinal Sialylation as a Novel Approach to Mitigating Allergic Reactions...

Sialic acids are crucial for maintaining intestinal homeostasis, but their role in food allergies remains poorly understood. This study investigates the regulatory function of sialic acid (Neu5Ac) in tropomyosin-induced allergic responses, with the aim of identifying potential therapeutic targets. In a C57BL/6N mouse model sensitized with shrimp tropomyosin, Neu5Ac treatment alleviated allergic symptoms, as evidenced by reduced anaphylaxis scores, lower levels of allergen-specific antibodies and Th2 cytokines, enhanced gut microbiota composition, and increased short-chain fatty acid production. To validate these findings, we used the sialyltransferase inhibitor 3Fax-Peracetyl Neu5Ac to inhibit sialylation in both the mouse and CMT93 cell models. Mice with reduced sialylation displayed more severe allergic symptoms, including diarrhea, elevated anaphylaxis scores, increased antibody levels, a Th2-skewed immune response, compromised intestinal barriers, and higher mortality rates. Similarly, in CMT93 cells, sialylation inhibition led to increased secretion of inflammatory markers and greater cellular permeability. These findings underscore the protective effects of Neu5Ac in alleviating food allergies and suggest that enhancing sialylation could provide a novel therapeutic strategy for managing allergic responses.