Research progress on the structure, function and bidirectional regulation mechanism of the enteric nervous system

doi:10.16098/j.issn.0529-1356.2026.06.018

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Acta Anatomica Sinica ›› 2026, Vol. 57 ›› Issue (5) : 656-662. DOI: 10.16098/j.issn.0529-1356.2026.06.018

Review

Research progress on the structure, function and bidirectional regulation mechanism of the enteric nervous system

TAO Xin-lei ¹, WANG Zi-xu ¹, WANG Da-qing ², DU Chen-guang ², CAO Gui-fang ², CHEN Yao-xing ¹, CAO Jing^1*

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Abstract

Commonly known as “the second brain”, the enteric nervous system (ENS) is a vital part of the autonomic nervous system that independently regulates gastrointestinal functions while also communicating with the central nervous system (CNS) through the gut-brain axis. The ENS originates from neural crest cells, primarily from vagal and sacral neural crests, and forms a ganglionic network composed of neurons and enteric glial cells (EGCs), including myenteric plexus and submucosal plexuses. ENS neurons can be categorized as sensory, interneurons, or motor neurons, and they utilize various neurotransmitters such as acetylcholine (Ach), 5-hydroxytryptamine (5-HT), nitric oxide (NO), and vasoactive intestinal peptide (VIP) to manage gastrointestinal (GI) motility, secretion, blood flow, and immune responses. Despite its important role, the ENS still lags the CNS due to its complex anatomy and unclear molecular markers. This review summarized the origin and development of the ENS, and clarified the functions of ENS neurons and the roles of various neurotransmitters in intestinal physiology. Additionally, we also summarized the bidirectional regulatory relationship between ENS and the intestinal mucosal immune barrier, immune cells, and microbiota, highlighting its crucial role in maintaining intestinal homeostasis.

Key words

Enteric nervous system / Neuron / Neurotransmitter / Mucosal immunity / Intestinal epithelial cell / Gut microbiota

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TAO Xin-lei , WANG Zi-xu , WANG Da-qing , DU Chen-guang , CAO Gui-fang , CHEN Yao-xing , CAO Jing. Research progress on the structure, function and bidirectional regulation mechanism of the enteric nervous system[J]. Acta Anatomica Sinica. 2026, 57(5): 656-662 https://doi.org/10.16098/j.issn.0529-1356.2026.06.018

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