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Antioxidants
Volume 14
Issue 6
10.3390/antiox14060732
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Lactobacillus fermentum ZC529 Protects Intestinal Epithelial Barrier Integrity by Activating the Keap1-Nrf2 Signaling Pathway and Inhibiting the NF-κB Signaling Pathway

by
Zian Yuan
1,2,3,†,
Lang Huang
1,2,†,
Zhenguo Hu
4,
Junhao Deng
1,2,
Yehui Duan
4,
Qian Jiang
1,2,
Bi’e Tan
1,2,5,
Xiaokang Ma
1,2,
Chen Zhang
1,5,6,* and
Xiongzhuo Tang
1,2,*
1
Hunan Provincial Key Laboratory for the Products Quality Regulation of Livestock and Poultry, College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China
2
Yuelushan Laboratory, Changsha 410128, China
3
Faculty of Agriculture, Kagoshima University, Korimoto, Kagoshima 8900065, Japan
4
Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha 410125, China
5
Institute of Yunnan Circular Agricultural Industry, Pu’er 665000, China
6
Anhui Provincial Key Laboratory of Livestock and Poultry Product Safety, Institute of Animal Husbandry and Veterinary Medicine, Anhui Academy of Agricultural Sciences, Hefei 230011, China
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Antioxidants 2025, 14(6), 732; https://doi.org/10.3390/antiox14060732 (registering DOI)
Submission received: 10 May 2025 / Revised: 7 June 2025 / Accepted: 12 June 2025 / Published: 14 June 2025
(This article belongs to the Special Issue Natural Antioxidants in Animal Nutrition)
Versions Notes

Abstract

The probiotic bacteria Lactobacillus fermentum ZC529 (L.f ZC529) has been identified from the colon of the Diannan small-ear (DSE) pig, but its intestinal protective function still lacks investigation. Here, we established a dextran sodium sulfate (DSS)-induced intestinal oxidative stress model in both Drosophila and porcine small intestinal epithelial (IPEC-J2) cell lines to explore the anti-oxidative and anti-inflammatory effects of L.f ZC529. The data showed that the intestinal colonization of L.f ZC529 counteracted DSS-induced intestinal oxidative stress and excessive reactive oxygen species (ROS) generation by activation of the CncC pathway, a homology of the nuclear factor erythroid 2-related factor 2 (Nrf2) in mammalian systems. Moreover, L.f ZC529 supplementation prevented flies from DSS-induced intestinal barrier damage, inflammation, abnormal excretory function, and shortened lifespan. Finally, L.f ZC529 also attenuated DSS-induced intestinal injury in the IPEC-J2 cell line by activating the Keap1-Nrf2 signaling and inhibiting the NF-κB signaling pathways. Together, this study unraveled the profound intestinal protective function of L.f ZC529 and provides its potential application as a new antioxidant in improving animal intestinal health as well as in developing a new probiotic in the food industry.
Keywords: Lactobacillus fermentum; antioxidant; anti-inflammation; Nrf2; NF-κB Lactobacillus fermentum; antioxidant; anti-inflammation; Nrf2; NF-κB

Share and Cite

MDPI and ACS Style

Yuan, Z.; Huang, L.; Hu, Z.; Deng, J.; Duan, Y.; Jiang, Q.; Tan, B.; Ma, X.; Zhang, C.; Tang, X. Lactobacillus fermentum ZC529 Protects Intestinal Epithelial Barrier Integrity by Activating the Keap1-Nrf2 Signaling Pathway and Inhibiting the NF-κB Signaling Pathway. Antioxidants 2025, 14, 732. https://doi.org/10.3390/antiox14060732

AMA Style

Yuan Z, Huang L, Hu Z, Deng J, Duan Y, Jiang Q, Tan B, Ma X, Zhang C, Tang X. Lactobacillus fermentum ZC529 Protects Intestinal Epithelial Barrier Integrity by Activating the Keap1-Nrf2 Signaling Pathway and Inhibiting the NF-κB Signaling Pathway. Antioxidants. 2025; 14(6):732. https://doi.org/10.3390/antiox14060732

Chicago/Turabian Style

Yuan, Zian, Lang Huang, Zhenguo Hu, Junhao Deng, Yehui Duan, Qian Jiang, Bi’e Tan, Xiaokang Ma, Chen Zhang, and Xiongzhuo Tang. 2025. "Lactobacillus fermentum ZC529 Protects Intestinal Epithelial Barrier Integrity by Activating the Keap1-Nrf2 Signaling Pathway and Inhibiting the NF-κB Signaling Pathway" Antioxidants 14, no. 6: 732. https://doi.org/10.3390/antiox14060732

APA Style

Yuan, Z., Huang, L., Hu, Z., Deng, J., Duan, Y., Jiang, Q., Tan, B., Ma, X., Zhang, C., & Tang, X. (2025). Lactobacillus fermentum ZC529 Protects Intestinal Epithelial Barrier Integrity by Activating the Keap1-Nrf2 Signaling Pathway and Inhibiting the NF-κB Signaling Pathway. Antioxidants, 14(6), 732. https://doi.org/10.3390/antiox14060732

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