Zeaxanthin as a potential regulator of intestinal immunity: effects on barrier function and metabolic profiles in diet-induced obesity

Abstract Long-term high-fat diet (HFD) leads to metabolic disorders and disrupts intestinal immune regulation. Zeaxanthin, a bioactive carotenoid known for antioxidant and immunomodulatory effects, has limited evidence regarding its role in obesity-triggered gut immune dysfunction. This study investigated zeaxanthin’s effects on intestinal barrier function, immune homeostasis, and metabolic profiles in HFD-induced obese mice. Results showed that zeaxanthin enhanced intestinal tight junction protein expression and elevated immune factors such as interleukin-10, secretory immunoglobulin A, and lysozyme. Flow cytometry revealed that zeaxanthin improved small intestinal antigen-presenting capacity, promoted CD4⁺ T cell activation, and partially reversed the HFD-induced Th17/Treg imbalance. By modulating the JAK/STAT signaling pathway, zeaxanthin improved the CIITA-MHC II axis, thereby restoring immune balance. A STAT1 inhibition assay using Fludarabine confirmed that zeaxanthin acts through STAT1 to upregulate CIITA and MHC II expression. Additionally, zeaxanthin altered intestinal metabolic profiles, particularly affecting tryptophan and phenylalanine metabolism. These findings demonstrate that zeaxanthin alleviates intestinal immune dysregulation in obesity via multiple pathways, providing a theoretical foundation and substantial support for developing functional foods targeting intestinal health.