The Gut-Brain Axis
The Gut-Brain Axis
复制标题
肠-脑轴
DOI：
10.1159/000512226
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发表时间：
2021-01
影响因子：
3.9
通讯作者：
N. Hattori;Y. Yamashiro
中科院分区：
文献类型：
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作者：
N. Hattori;Y. Yamashiro
肠脑轴（GBA）的概念已经存在了30多年[1]。胃肠道运动和感觉成分向中枢神经系统（CNS）发送信息，对肠道的返回反应是GBA的定义[2]。营养影响微生物群定植和肠道代谢物，这可以通过神经，免疫和内分泌途径影响大脑发育和功能[3]。大脑是GBA的中心组成部分，包括大脑皮层、边缘系统、下丘脑-垂体轴和大脑系统之间的连接。边缘系统接收来自包括海马体在内的其他大脑区域的输入，海马体负责一系列行为[4]。GBA的外周成分通过肠神经系统、自主神经系统和交感神经系统与CNS通信[5，6]。位于肠壁内的肠神经系统通过迷走神经、背根和结状神经节与大脑沟通[5]。下丘脑-垂体轴、自主神经系统和交感神经系统是GBA的整合外周成分[7]。迷走传入神经是从肠道到大脑的主要逆行信号系统[8]。基于传出迷走神经的胆碱能抗炎通路调节肿瘤坏死因子-α与巨噬细胞响应肠道应激信号分泌的其他细胞因子之间的平衡[9]。这种炎症可导致肠上皮屏障功能丧失，从而允许细菌侵入。细菌入侵通过病原体相关分子模式（包括脂多糖（LPS，内毒素），其是触发肠道炎症的识别受体）导致肠道通透性增加以及免疫和体细胞活化[6]。通过全身和肠道免疫系统通过GBA发送的信号导致脑功能和疾病的改变。在压力状态下，肠道中的激素和神经肽分泌最终通过下丘脑的信号引起肾上腺释放皮质醇。GBA通过去甲肾上腺素和神经肽信使（例如血管活性肠肽）影响肠免疫细胞，并且这些信使调节位于整个肠壁和次级淋巴组织（例如派尔集合淋巴结）中的树突状细胞和T细胞的功能。关于肠道微生物组，免疫系统调节大脑发育的能力已经得到认可[3]，研究人员提出了肠道微生物影响长期大脑功能发育编程的关键窗口。利息-
The concept of the gut-brain axis (GBA) has existed for more than 3 decades [1]. Gastrointestinal motor and sensory components send messages to the central nervous system (CNS), and the return response to the intestine is the definition of the GBA [2]. Nutrition affects microbiota colonization and gut metabolites, which can influence brain development and function through neural, immunological, and endocrine pathways [3]. The brain is the central component of the GBA and includes connections between the cerebral cortex, the limbic system, the hypothalamic-pituitary axis, and the brain system. The limbic system receives input from other brain regions including the hippocampus, which is responsible for a range of behaviors [4]. The peripheral components of the GBA communicate with the CNS through the enteric, autonomic, and sympathetic nervous systems [5, 6]. The enteric nervous system, which resides within the intestinal wall, communicates with the brain via the vagus nerve, dorsal root, and nodose ganglia [5]. The hypothalamicpituitary axis, the autonomic nervous system, and the sympathetic nervous system are integrated peripheral components of the GBA [7]. The afferent vagus nerve is a major retrograde signaling system from the gut to the brain [8]. The efferent vagus nerve-based cholinergic anti-inflammatory pathway regulates the balance between tumor necrosis factor-α and other cytokines secreted by macrophages in response to stress signals in the gut [9]. This inflammation can result in the loss of intestinal epithelial barrier function, which allows bacterial invasion. Bacterial invasion leads to an increase in intestinal permeability and activation of immune and somatic cells through pathogen-associated molecular patterns including lipopolysaccharides (LPS, endotoxin), which are recognition receptors that trigger inflammation in the gut [6]. Signals sent through the systemic and intestinal immune system via the GBA cause alterations in brain function and disease. During a state of stress, hormone and neuropeptide secretion in the gut ultimately invokes cortisol release from the adrenal gland via signals though the hypothalamus. The GBA influences intestinal immune cells via norepinephrine and neuropeptide messengers, such as vasoactive intestinal peptide, and these modulate the function of dendritic cells and T cells located throughout the wall of the intestine and in secondary lymphoid tissues, such as Peyer’s patches. Regarding the gut microbiome, the ability of the immune system to modulate brain development has been recognized [3], and researchers have proposed a critical window for intestinal microbes to influence developmental programming of long-lasting brain function. Interest-