Enteroendocrine cell regulation of the gut-brain axis.
Enteroendocrine cell regulation of the gut-brain axis.
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DOI：
10.3389/fnins.2023.1272955
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发表时间：
2023
影响因子：
4.3
通讯作者：
Waldman, Scott A.
中科院分区：
文献类型：
--
作者：
Barton, Joshua R.;Londregan, Annie K.;Alexander, Tyler D.;Entezari, Ariana A.;Covarrubias, Manuel;Waldman, Scott A.
关键词：
肠内分泌细胞(EECS)是肠道和大脑之间的重要接口，它传递有关营养、疼痛的信号，甚至是来自我们微生物组的信息。EEC是一种激素产生细胞，表达于整个胃肠道上皮细胞，已被用于治疗糖尿病和控制体重的Semagluide(Ozempic，Wegoy)、Terzepatide(Munjaro)和retatruide(第二阶段)以及Linaclotie(Linzess)等药物用于治疗肠易激综合征(IBS)和内脏疼痛。本文就肠上皮细胞在肠腔至脑的信号传递中的作用作一综述。通常情况下，EEC通过各种激素传递有关肠道环境的信息，根据每种细胞类型分泌的激素将EEC分为不同的类别。最近的研究揭示了更多不同的EECS激素谱和通讯方式，包括与周围神经元的直接突触通讯。EEC被称为神经足细胞，通过与迷走神经和初级感觉神经元的直接通信，迅速将信号从肠道传递到大脑。此外，本文还讨论了EECS中复杂的信息处理机制，包括转导腔内信号的受体和控制这些信号的启动和传播的离子通道补体。为了安全地治疗肠易激综合征和肥胖等破坏性和普遍性的疾病，有必要加深对EEC生理学的了解。
Enteroendocrine cells (EECs) are an essential interface between the gut and brain that communicate signals about nutrients, pain, and even information from our microbiome. EECs are hormone-producing cells expressed throughout the gastrointestinal epithelium and have been leveraged by pharmaceuticals like semaglutide (Ozempic, Wegovy), terzepatide (Mounjaro), and retatrutide (Phase 2) for diabetes and weight control, and linaclotide (Linzess) to treat irritable bowel syndrome (IBS) and visceral pain. This review focuses on role of intestinal EECs to communicate signals from the gut lumen to the brain. Canonically, EECs communicate information about the intestinal environment through a variety of hormones, dividing EECs into separate classes based on the hormone each cell type secretes. Recent studies have revealed more diverse hormone profiles and communication modalities for EECs including direct synaptic communication with peripheral neurons. EECs known as neuropod cells rapidly relay signals from gut to brain via a direct communication with vagal and primary sensory neurons. Further, this review discusses the complex information processing machinery within EECs, including receptors that transduce intraluminal signals and the ion channel complement that govern initiation and propagation of these signals. Deeper understanding of EEC physiology is necessary to safely treat devastating and pervasive conditions like irritable bowel syndrome and obesity.
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