Kallyope, Inc., 430 East 29th, Street, New York, NY, 10016, USA.
Mol Metab. 2021 Apr;46:101175. doi: 10.1016/j.molmet.2021.101175. Epub 2021 Feb 3.
The gut-brain axis, which mediates bidirectional communication between the gastrointestinal system and central nervous system (CNS), plays a fundamental role in multiple areas of physiology including regulating appetite, metabolism, and gastrointestinal function. The biology of the gut-brain axis is central to the efficacy of glucagon-like peptide-1 (GLP-1)-based therapies, which are now leading treatments for type 2 diabetes (T2DM) and obesity. This success and research to suggest a much broader role of gut-brain circuits in physiology and disease has led to increasing interest in targeting such circuits to discover new therapeutics. However, our current knowledge of this biology is limited, largely because the scientific tools have not been available to enable a detailed mechanistic understanding of gut-brain communication.
In this review, we provide an overview of the current understanding of how sensory information from the gastrointestinal system is communicated to the central nervous system, with an emphasis on circuits involved in regulating feeding and metabolism. We then describe how recent technologies are enabling a better understanding of this system at a molecular level and how this information is leading to novel insights into gut-brain communication. We also discuss current therapeutic approaches that leverage the gut-brain axis to treat diabetes, obesity, and related disorders and describe potential novel approaches that have been enabled by recent advances in the field.
The gut-brain axis is intimately involved in regulating glucose homeostasis and appetite, and this system plays a key role in mediating the efficacy of therapeutics that have had a major impact on treating T2DM and obesity. Research into the gut-brain axis has historically largely focused on studying individual components in this system, but new technologies are now enabling a better understanding of how signals from these components are orchestrated to regulate metabolism. While this work reveals a complexity of signaling even greater than previously appreciated, new insights are already being leveraged to explore fundamentally new approaches to treating metabolic diseases.
肠道-大脑轴（gut-brain axis）介导胃肠道系统与中枢神经系统（CNS）之间的双向通讯，在包括调节食欲、代谢和胃肠道功能在内的多个生理领域发挥着基本作用。肠道-大脑轴的生物学是基于胰高血糖素样肽-1（GLP-1）的治疗方法（目前是 2 型糖尿病（T2DM）和肥胖症的主要治疗方法）的疗效的核心。这种成功以及研究表明肠道-大脑回路在生理和疾病中有更广泛的作用，这导致了人们对靶向这些回路以发现新疗法的兴趣日益增加。然而，我们对这种生物学的了解有限，主要是因为缺乏科学工具来实现对肠道-大脑通讯的详细机制理解。
在这篇综述中，我们概述了目前对胃肠道系统的感觉信息如何传递到中枢神经系统的理解，重点介绍了参与调节进食和代谢的回路。然后，我们描述了最近的技术如何使我们能够在分子水平上更好地理解这个系统，以及这些信息如何为肠道-大脑通讯提供新的见解。我们还讨论了利用肠道-大脑轴治疗糖尿病、肥胖症和相关疾病的当前治疗方法，并描述了该领域最近的进展所带来的潜在新方法。
肠道-大脑轴密切参与调节血糖稳态和食欲，该系统在介导对 T2DM 和肥胖症治疗产生重大影响的治疗方法的疗效方面发挥着关键作用。肠道-大脑轴的研究历史上主要集中在研究该系统中的单个组件，但新技术现在使我们能够更好地理解这些组件的信号如何协调以调节代谢。虽然这项工作揭示了比以前预期更复杂的信号复杂性，但新的见解已经被利用来探索治疗代谢疾病的根本新方法。
