Wu Huixian, Ding Chenchen, Chi Chunyan, Liu Shuhui, Gao Zhangshan, Sun Weidong, Zhao Haiming, Song Suquan
MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China.
Pure&Natural (Shanghai) Biotechnology Co., Ltd., Shanghai, 201112, China.
Probiotics Antimicrob Proteins. 2024 Jun 3. doi: 10.1007/s12602-024-10294-4.
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.
鼠伤寒沙门氏菌是一个主要的公共卫生问题。我们之前已经证明卷曲乳杆菌7-4（L. crispatus 7-4）能够抑制鼠伤寒沙门氏菌的生长，因此可以作为一种生物防治策略来抑制食源性鼠伤寒沙门氏菌感染。然而，卷曲乳杆菌7-4的抑制作用及其深入机制仍有待阐明。在本研究中，我们发现卷曲乳杆菌7-4可通过促进肠道屏障完整性、维持肠道黏膜屏障稳态以及减轻肠道炎症反应来预防鼠伤寒沙门氏菌诱导的回肠损伤。此外，我们证明该益生菌菌株可增加乳酸杆菌属的丰度以维持微生物稳态，并同时通过激活谷胱甘肽代谢途径增加γ-谷氨酰半胱氨酸（γ-GC）的量。增加的γ-GC促进了Nrf2靶基因的转录，从而提高宿主抗氧化水平、减少活性氧（ROS）积累并清除促炎细胞因子。换句话说，卷曲乳杆菌7-4可通过提高γ-GC激活肠上皮细胞Nrf2途径，以预防鼠伤寒沙门氏菌诱导的肠道炎症和氧化损伤。
