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Lactobacillus crispatus 7-4 Mitigates Salmonella typhimurium-Induced Enteritis via the γ‑Glutamylcysteine-Mediated Nrf2 Pathway

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Abstract

Salmonella typhimurium (S. typhimurium) constitutes a major public health concern. We have previously proven that Lactobacillus crispatus 7-4 (L. crispatus 7-4) can inhibit the growth of S. typhimurium and thus can be used as a biocontrol strategy to suppress foodborne S. typhimurium infections. However, the inhibitory effect and in-depth mechanism of L. crispatus 7-4 remain to be elucidated. In this study, we found that L. crispatus 7-4 can protect against S. typhimurium-induced ileum injury by promoting intestinal barrier integrity, maintaining intestinal mucosal barrier homeostasis, and reducing intestinal inflammatory response. Furthermore, we demonstrated that this probiotic strain can increase the abundance of Lactobacillus spp. to maintain microbial homeostasis and simultaneously increase the amount of γ‑glutamylcysteine (γ-GC) by activating the glutathione metabolic pathway. The increased γ-GC promoted the transcription of Nrf2 target genes, thereby improving the host antioxidant level, reducing reactive oxygen species (ROS) accumulation, and removing pro-inflammatory cytokines. In other words, L. crispatus 7-4 could activate the enterocyte Nrf2 pathway by improving γ-GC to protect against S. typhimurium-induced intestinal inflammation and oxidative damage.

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Acknowledgements

We would like to thank Yuting Wu, Shuo Zhang, Jiwen Liu and Meihua Zhang for helping with the necropsy of experimental animals.

Funding

This work was supported by the National Key R&D Program (2022YFC2105005), the Forestry Science and Technology Innovation and Promotion Project of Jiangsu Province (LYKJ [2021]40), and the Priority Academic Program Development of Jiangsu Higher Education Institutions.

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Author notes

  1. Huixian Wu, Chenchen Ding and Chunyan Chi are contributed equally to this work.

Authors and Affiliations

  1. MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China

    Huixian Wu, Chenchen Ding, Shuhui Liu, Zhangshan Gao, Weidong Sun & Suquan Song

  2. Pure&Natural (Shanghai) Biotechnology Co., Ltd., Shanghai, 201112, China

    Chunyan Chi & Haiming Zhao

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Contributions

SS and WH designed the experiments. WH, DC, and CC carried out animal experiment, data analysis, and drafted the manuscript. WH and LS did the cell culture. GZ analyzed the qRT-PCR. WH and DC wrote the manuscript. CC revised the paper. SS, SW, and ZH reviewed the manuscript.

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Correspondence to Suquan Song.

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Wu, H., Ding, C., Chi, C. et al. Lactobacillus crispatus 7-4 Mitigates Salmonella typhimurium-Induced Enteritis via the γ‑Glutamylcysteine-Mediated Nrf2 Pathway. Probiotics & Antimicro. Prot. (2024). https://doi.org/10.1007/s12602-024-10294-4

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