Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry, College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Tianjin, China.
Tianjin Key Laboratory of Animal and Plant Resistance, College of Life Sciences, Tianjin Normal University, Tianjin, China.
Front Immunol. 2021 Nov 11;12:771826. doi: 10.3389/fimmu.2021.771826. eCollection 2021.
(CB) can enhance antioxidant capacity and alleviate oxidative damage, but the molecular mechanism by which this occurs remains unclear. This study used enterotoxigenic (ETEC) K88 as a pathogenic model, and the p62-Keap1-Nrf2 signaling pathway and intestinal microbiota as the starting point to explore the mechanism through which CB alleviates oxidative damage. After pretreatment with CB for 15 d, mice were challenged with ETEC K88 for 24 h. The results suggest that CB pretreatment can dramatically reduce crypt depth (CD) and significantly increase villus height (VH) and VH/CD in the jejunum of ETEC K88-infected mice and relieve morphological lesions of the liver and jejunum. Additionally, compared with ETEC-infected group, pretreatment with 4.4×10 CFU/mL CB can significantly reduce malondialdehyde (MDA) level and dramatically increase superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels in the serum. This pretreatment can also greatly increase the mRNA expression levels of tight junction proteins and genes related to the p62-Keap1-Nrf2 signaling pathway in the liver and jejunum in ETEC K88-infected mice. Meanwhile, 16S rDNA amplicon sequencing revealed that was significantly enriched after ETEC K88 challenge relative to the control group, while was significantly enriched after 4.4×10 CFU/mL CB treatment. Furthermore, 4.4×10 CFU/mL CB pretreatment increased the short-chain fatty acid (SCFA) contents in the cecum of ETEC K88-infected mice. Moreover, we found that , , , , , and are closely related to SCFA contents and oxidative indicators. Taken together, 4.4×10 CFU/mL CB pretreatment can alleviate ETEC K88-induced oxidative damage through activating the p62-Keap1-Nrf2 signaling pathway and remodeling the cecal microbiota community in mice.
（CB）可以增强抗氧化能力并减轻氧化损伤，但具体的分子机制尚不清楚。本研究以肠产毒性大肠杆菌（ETEC）K88 为致病模型，以 p62-Keap1-Nrf2 信号通路和肠道微生物组为切入点，探讨 CB 缓解氧化损伤的作用机制。用 CB 预处理 15 d 后，用 ETEC K88 对小鼠进行 24 h 攻毒。结果表明，CB 预处理可显著降低 ETEC K88 感染小鼠空肠隐窝深度（CD），显著增加绒毛高度（VH）和 VH/CD，缓解肝和空肠的形态损伤；与 ETEC 感染组相比，4.4×10 CFU/mL CB 预处理可显著降低 MDA 水平，显著增加血清中超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-Px）水平；该预处理还可显著增加 ETEC K88 感染小鼠肝和空肠中与 p62-Keap1-Nrf2 信号通路相关的紧密连接蛋白和基因的 mRNA 表达水平。同时，16S rDNA 扩增子测序结果表明，与对照组相比，ETEC K88 攻毒后 显著富集，而 4.4×10 CFU/mL CB 处理后 显著富集；此外，4.4×10 CFU/mL CB 预处理可增加 ETEC K88 感染小鼠盲肠中的短链脂肪酸（SCFA）含量。并且，我们发现 、 、 、 、 和 与 SCFA 含量和氧化指标密切相关。综上所述，4.4×10 CFU/mL CB 预处理可通过激活 p62-Keap1-Nrf2 信号通路和重塑小鼠盲肠微生物群落来缓解 ETEC K88 诱导的氧化损伤。
