Division of Histology and Embryology, International Joint Laboratory for Embryonic Development & Prenatal Medicine, Medical College, Jinan University, Guangzhou 510632, China; The First Affiliated Hospital of Jinan University, Guangzhou 510632, China.
Division of Histology and Embryology, International Joint Laboratory for Embryonic Development & Prenatal Medicine, Medical College, Jinan University, Guangzhou 510632, China.
Pharmacol Res. 2021 May;167:105543. doi: 10.1016/j.phrs.2021.105543. Epub 2021 Mar 10.
In this study, we identified elevated levels of LPS and suppressed neurogenesis in a successfully established mouse model of gut microbiota dysbiosis. We mimicked these phenotypes using mouse and chicken embryos exposed to LPS and found that dramatic variation in gene expression was due to changes in the dorsal-ventral patterning of the neural tube. Cell survival and excess ROS were also involved in this process. Antioxidant administration alleviated LPS-activated NF-κB signaling, while directly blocking NF-κB signaling altered the LPS-induced inhibition of neurogenesis. Furthermore, IL-6 was proven to play a vital role in the expression of crucial neurogenesis-related genes and NF-κB. In summary, we found that the suppression of neurogenesis induced by dysbacteriosis-derived LPS was significantly reversed in mice with fecal microbiota transplantation. This study reveals that gut dysbacteriosis-derived LPS impairs embryonic neurogenesis, and that the NF-κB/IL-6 pathway could be one of the main factors triggering the downstream signaling cascade.
在这项研究中，我们在一个成功建立的肠道微生物失调小鼠模型中发现了 LPS 水平升高和神经发生受抑制的现象。我们使用暴露于 LPS 的小鼠和鸡胚模拟了这些表型，发现基因表达的巨大变化是由于神经管的背-腹模式发生了变化。细胞存活和过量的 ROS 也参与了这一过程。抗氧化剂的给予缓解了 LPS 激活的 NF-κB 信号，而直接阻断 NF-κB 信号则改变了 LPS 诱导的神经发生抑制。此外，IL-6 被证明在关键神经发生相关基因和 NF-κB 的表达中发挥着重要作用。总之，我们发现，由肠道微生物失调衍生的 LPS 引起的神经发生抑制在粪便微生物移植的小鼠中得到了显著逆转。这项研究表明，肠道微生物失调衍生的 LPS 损害了胚胎神经发生，而 NF-κB/IL-6 途径可能是触发下游信号级联的主要因素之一。
