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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.
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Acknowledgements
This work was supported by funding from the National Natural Science Foundation of China (No. 32201955). All methods are reported in accordance with ARRIVE guidelines
Authors and Affiliations
College of Food Science and Engineering, Jilin Agricultural University, Changchun, China
Hao Zhang, Yuechen Jin, Zhina Hao, Yuan Chen, Weiyuan Ren, Qianxi Zang & Meihong Liu
National Engineering Research Center of Wheat and Corn Deep Processing, Changchun, China
Hao Zhang, Yuechen Jin, Zhina Hao, Yuan Chen, Weiyuan Ren, Qianxi Zang & Meihong Liu
Key Laboratory of TCM Pharmacology, Jilin Academy of Chinese Medicine Sciences, Changchun, China
Hongyu Zhao
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- Hao ZhangView author publications
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- Yuechen JinView author publications
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- Hongyu ZhaoView author publications
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- Zhina HaoView author publications
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- Yuan ChenView author publications
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- Weiyuan RenView author publications
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- Qianxi ZangView author publications
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- Meihong LiuView author publications
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Zhang, H., Jin, Y., Zhao, H. et al. Zeaxanthin as a potential regulator of intestinal immunity: effects on barrier function and metabolic profiles in diet-induced obesity.
npj Sci Food (2026). https://doi.org/10.1038/s41538-026-00997-z
Received:09 December 2025
Accepted:06 July 2026
Published:21 August 2026
DOI
:https://doi.org/10.1038/s41538-026-00997-z
