Department of Critical Care Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China.
Int J Mol Sci. 2023 Jun 28;24(13):10820. doi: 10.3390/ijms241310820.
Traumatic brain injury refers to the damage caused to intracranial tissues by an external force acting on the head, leading to both immediate and prolonged harmful effects. Neuroinflammatory responses play a critical role in exacerbating the primary injury during the acute and chronic phases of TBI. Research has demonstrated that numerous neuroinflammatory responses are mediated through the "microbiota-gut-brain axis," which signifies the functional connection between the gut microbiota and the brain. The aryl hydrocarbon receptor (AhR) plays a vital role in facilitating communication between the host and microbiota through recognizing specific ligands produced directly or indirectly by the microbiota. Tryptophan (trp), an indispensable amino acid in animals and humans, represents one of the key endogenous ligands for AhR. The metabolites of trp have significant effects on the functioning of the central nervous system (CNS) through activating AHR signalling, thereby establishing bidirectional communication between the gut microbiota and the brain. These interactions are mediated through immune, metabolic, and neural signalling mechanisms. In this review, we emphasize the co-metabolism of tryptophan in the gut microbiota and the signalling pathway mediated by AHR following TBI. Furthermore, we discuss the impact of these mechanisms on the underlying processes involved in traumatic brain injury, while also addressing potential future targets for intervention.
创伤性脑损伤是指外力作用于头部导致颅内组织损伤，引起即刻和长期的有害影响。神经炎症反应在 TBI 的急性和慢性阶段加剧原发性损伤中起着关键作用。研究表明，许多神经炎症反应是通过“微生物群-肠道-大脑轴”介导的，这表明了肠道微生物群和大脑之间的功能联系。芳基烃受体 (AhR) 通过识别微生物群直接或间接产生的特定配体，在促进宿主与微生物群之间的交流方面发挥着重要作用。色氨酸 (trp) 是动物和人类必需的氨基酸，是 AhR 的关键内源性配体之一。trp 的代谢物通过激活 AHR 信号转导对中枢神经系统 (CNS) 的功能产生重大影响，从而在肠道微生物群和大脑之间建立双向通讯。这些相互作用是通过免疫、代谢和神经信号转导机制介导的。在这篇综述中，我们强调了创伤性脑损伤后肠道微生物群中 tryptophan 的共代谢以及 AHR 介导的信号通路。此外，我们讨论了这些机制对创伤性脑损伤相关过程的影响，同时也探讨了潜在的干预靶点。
