Department of Human Molecular Genetics, University Hospital Heidelberg, Heidelberg, Germany.
Interdisciplinary Center for Neurosciences (IZN), Heidelberg University, Heidelberg, Germany.
Nat Rev Gastroenterol Hepatol. 2021 Jun;18(6):393-410. doi: 10.1038/s41575-020-00385-2. Epub 2021 Jan 29.
The enteric nervous system (ENS) is the largest division of the peripheral nervous system and closely resembles components and functions of the central nervous system. Although the central role of the ENS in congenital enteric neuropathic disorders, including Hirschsprung disease and inflammatory and functional bowel diseases, is well acknowledged, its role in systemic diseases is less understood. Evidence of a disordered ENS has accumulated in neurodegenerative diseases ranging from amyotrophic lateral sclerosis, Alzheimer disease and multiple sclerosis to Parkinson disease as well as neurodevelopmental disorders such as autism. The ENS is a key modulator of gut barrier function and a regulator of enteric homeostasis. A 'leaky gut' represents the gateway for bacterial and toxin translocation that might initiate downstream processes. Data indicate that changes in the gut microbiome acting in concert with the individual genetic background can modify the ENS, central nervous system and the immune system, impair barrier function, and contribute to various disorders such as irritable bowel syndrome, inflammatory bowel disease or neurodegeneration. Here, we summarize the current knowledge on the role of the ENS in gastrointestinal and systemic diseases, highlighting its interaction with various key players involved in shaping the phenotypes. Finally, current flaws and pitfalls related to ENS research in addition to future perspectives are also addressed.
肠神经系统（ENS）是外周神经系统中最大的分支，其结构和功能与中枢神经系统非常相似。尽管 ENS 在先天性肠神经病，包括先天性巨结肠和炎症性及功能性肠病中的核心作用已得到广泛认可，但它在系统性疾病中的作用尚未被充分了解。在从肌萎缩侧索硬化症、阿尔茨海默病和多发性硬化症到帕金森病等神经退行性疾病，以及自闭症等神经发育障碍中，都积累了 ENS 紊乱的证据。ENS 是肠道屏障功能的关键调节因子，也是肠道内稳态的调节剂。“肠漏”代表了细菌和毒素易位的门户，可能引发下游过程。数据表明，肠道微生物组的变化与个体遗传背景协同作用，可能会改变 ENS、中枢神经系统和免疫系统，损害屏障功能，并导致各种疾病，如肠易激综合征、炎症性肠病或神经退行性疾病。本文总结了 ENS 在胃肠道和系统性疾病中的作用的最新知识，强调了其与参与表型形成的各种关键因素的相互作用。最后，还讨论了 ENS 研究目前存在的缺陷和陷阱以及未来的展望。
