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Review
. 2016 May;28(5):620-30.
doi: 10.1111/nmo.12754. Epub 2015 Dec 21.

Enteroendocrine cells: a review of their role in brain-gut communication

R Latorre  1 , C Sternini  2 , R De Giorgio  3 , B Greenwood-Van Meerveld  1   4
Affiliations
Review

Enteroendocrine cells: a review of their role in brain-gut communication

R Latorre et al. Neurogastroenterol Motil. 2016 May.

Abstract

Background: Specialized endoderm-derived epithelial cells, that is, enteroendocrine cells (EECs), are widely distributed throughout the gastrointestinal (GI) tract. Enteroendocrine cells form the largest endocrine organ in the body and play a key role in the control of GI secretion and motility, the regulation of food intake, postprandial glucose levels and metabolism. EECs sense luminal content and release signaling molecules that can enter the circulation to act as classic hormones on distant targets, act locally on neighboring cells and on distinct neuronal pathways including enteric and extrinsic neurons. Recent studies have shed light on EEC sensory transmission by showing direct connections between EECs and the nervous system via axon-like processes that form a well-defined neuroepithelial circuits through which EECs can directly communicate with the neurons innervating the GI tract to initiate appropriate functional responses.

Purpose: This review will highlight the role played by the EECs in the complex and integrated sensory information responses, and discuss the new findings regarding EECs in the brain-gut axis bidirectional communication.

Keywords: afferent neurons; gut chemosensing; peptides.

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Figures

Figure 1
Figure 1. Enteroendocrine cells (EECs) Subpopulations in the Gastrointestinal Tract
EECs comprise different subgroups producing and releasing a variety of hormones under appropriate stimulation. EECs are largely distributed in the gut. The stomach corpus is rich in A cells secreting ghrelin (dark red circle), the antrum is populated by G cells secreting gastrin (purple circle), while in the pylorum there is a high density of D cells secreting somatostatin (red circle). D cells are also present in the proximal segment of the small intestine. I (dark blue circle) and K (orange circle) cells, which secrete CCK and GIP, respectively, are located in the small intestine and L cells secreting GLP-1, GLP-2 and PYY (light blue circle) are widely distributed in the distal small intestine and in the colon (mainly in the proximal portion). Up to 95% of the total 5-HT is produced in the GI tract. EC (green circle) are situated in the pylorus, small and large intestine. 5-HT is also released by I cells (dark blue circle) located in the distal portion of the small intestine and L cells (light blue circle) in the large intestine. Only some example of EECs subgroups and relative hormones secreted are represented in the figure. Abbreviations: EC, enterochromaffin cell; 5-HT, 5-hydroxytryptamine; CCK, cholecystokinin; GLP-1, glucagon like peptide-1; GLP-2, Glucagon like peptide-2; PYY, peptide YY; GIP, gastric inhibitory peptide. EEC with short or long basal cytoplasmic processes.
Figure 2
Figure 2. EECs in the Brain-Gut Axis Bidirectional Communication
Green and Orange arrows indicate the bidirectional interplay referred to brain-gut axis, which include the mucosal EECs, ENS, vagus nerve, spinal cord and CNS. The basal cytoplasmic processes have a role in activating intrinsic and extrinsic sensory neurons. The activation of EECs may leads to sensitization via direct cell to neurons contact. Hormones released by EECs upon stimulation act on receptors located on the vagal and spinal neurons and influence neuronal pathways in the bidirectional brain-gut communication. Open type EECs sense luminal content and make contact with enteric nervous system (black), vagal nerve (afferent and efferent pathways, violet lines) and spinal nerve (afferent and efferent pathways, blue lines), closed-type EEC also contribute to activate these feedback signals from the gut to the brain. Together, this information sends positive or negative feedback to the brain (CNS), which modulates functions of the GI tract, glucose homeostasis and satiety. Moreover, impairment in the brain-gut axis pathways could be implicated in obesity, visceral hypersensitivity, intestinal disorders such as irritable bowel syndrome and inflammatory disorders such as inflammatory bowel disease. Abbreviations: NTS, nucleus tractus solitarii; DRG, dorsal root ganglia; ENS, enteric nervous system (myenteric and submucosal plexus); EEC, enteroendocrine cell.
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