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Dietary Zinc Ameliorates TNBS-Induced Colitis in Mice Associated with Regulation of Th1/Th2/Th17 Balance and NF-κB/NLRP3 Signaling Pathway

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Abstract

Inflammatory bowel diseases (IBDs), including Crohn’s disease and ulcerative colitis, are chronic relapsing inflammatory gastrointestinal tract diseases of uncertain origin, which are frequently associated with zinc deficiency. Animal models have a considerable value in elucidating the process of IBD. In this study, 50 male C57BL/6 J mice were randomly assigned to five groups: control group (Con), 2,4,6-trinitrobenzenesulfonic acid (TNBS) group, and three zinc supplementation groups, namely 160 ppm group, 400 ppm group, and 1000 ppm group. The results showed that supplementation of dietary zinc with zinc oxide could effectively relieve the severity of ulcerative colitis induced by TNBS in mice. We demonstrate that the protective mechanism involves the immunomodulation of dietary zinc by increasing CD3+, CD3+CD8+, and Th2 cells, suppressing Th1 and Th17 cells, and decreasing the production of serum IL-1β and IL-18. The dietary zinc oxide seems to be able to suppress the NF-κB/NLRP3 signaling pathway by downregulating the mRNA and protein expression of NIK, IKK, NF-κB, and NLRP3. The results suggest that dietary supplementation of zinc oxide may protect against colitis, and proper daily zinc supplementation may reduce the risk of IBD.

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The original contributions presented in the study are included in the article/supplementary material, and further inquiries can be directed to the corresponding author.

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Acknowledgements

We thank all members of Sichuan Youngster Technology Co., Ltd., provided technical support assistance in HE slices making and Flow cytometry.

Funding

This work was supported by Chengdu University (2081921001) and Training Program for Innovation and Entrepreneurship of Chengdu University (S202211079126).

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Authors and Affiliations

  1. School of Pharmacy, Sichuan Industrial Institute of Antibiotics, Chengdu University, No. 2025, Chengluo Avenue, Chengdu, 610106, Sichuan, China

    Changlin Wen, Jiayu Wang, Rao Zhong & Xi Peng

  2. Department of Technology, Sichuan Youngster Technology Co., Ltd., No. 733, Furong Avenue, Wenjiang District, Chengdu, 611130, Sichuan, China

    Zhenhua Sun, Mengjie Li & Xuemei Shen

  3. School of Basic Medicine Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, Sichuan, China

    Qiaobo Ye & Kaihua Qin

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  1. Changlin Wen
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Contributions

Management and supervision: XP. Experimental operation: CW, JW, ZS, RZ, ML, and XS. Data collation and analysis: CW, JW, ZS, and KQ. Article writing: CW and ML. Paper revision and editing: XP and QY. The authors contributed to the article and approve the final submitted version of the manuscript.

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Correspondence to Xi Peng.

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Wen, C., Wang, J., Sun, Z. et al. Dietary Zinc Ameliorates TNBS-Induced Colitis in Mice Associated with Regulation of Th1/Th2/Th17 Balance and NF-κB/NLRP3 Signaling Pathway. Biol Trace Elem Res 202, 659–670 (2024). https://doi.org/10.1007/s12011-023-03715-y

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