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  • Review Article
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The digestive neuronal–glial–epithelial unit: a new actor in gut health and disease

Nature Reviews Gastroenterology & Hepatology volume 10, pages 90–100 (2013)Cite this article

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Abstract

The monolayer of columnar epithelial cells lining the gastrointestinal tract—the intestinal epithelial barrier (IEB)—is the largest exchange surface between the body and the external environment. The permeability of the IEB has a central role in the regulation of fluid and nutrient intake as well as in the control of the passage of pathogens. The functions of the IEB are highly regulated by luminal as well as internal components, such as bacteria or immune cells, respectively. Evidence indicates that two cell types of the enteric nervous system (ENS), namely enteric neurons and enteric glial cells, are potent modulators of IEB functions, giving rise to the novel concept of a digestive 'neuronal–glial–epithelial unit' akin to the neuronal–glial–endothelial unit in the brain. In this Review, we summarize findings demonstrating that the ENS is a key regulator of IEB function and is actively involved in pathologies associated with altered barrier function.

Key Points

  • Altered functioning of the intestinal epithelial barrier (IEB) has a central role in the aetiology of a wide range of diseases; efficient IEB healing is essential to maintain IEB homeostasis

  • An anatomical unit comprised of enteric neurons, enteric glial cells and intestinal epithelial cells sets the basis for a functional digestive neuronal–glial–epithelial unit

  • Enteric neuromediators as well as gliomediators can differentially modulate major IEB functions such as paracellular permeability, intestinal epithelial cell proliferation and wound healing

  • Changes in the phenotype of enteric neurons and glial cells occur in various diseases but the involvement of the enteric nervous system (active or bystander) in these pathologies remains to be defined

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Figure 1: Junctional complexes regulating epithelial cells interactions.
Figure 2: The ENS forms a complex network in close proximity to the IEB.
Figure 3: Soluble factors produced by the ENS regulate IEB functions.

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Acknowledgements

Work in our laboratory is financed by grants from the INSERM, University of Nantes, Fondation pour la Recherche Médicale, INCa, ANR-EnteNeurObesity, INSERM-DHOS, Ligue contre le Cancer, Fondation SanTDige, France Parkinson, Michael J. Fox Fondation, CECAP (Comité d'Entente et de Coordination des Associations de Parkinsoniens) and Parkinsoniens de Vendée.

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  1. INSERM UMR913, Institut des Maladies de l'Appareil Digestif, Université de Nantes, CHU Hôtel Dieu, 1 place Alexis Ricordeau, Nantes, 44093, France

    Michel Neunlist, Laurianne Van Landeghem, Maxime M. Mahé, Pascal Derkinderen, Stanislas Bruley des Varannes & Malvyne Rolli-Derkinderen

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  1. Michel Neunlist
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  2. Laurianne Van Landeghem
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  6. Malvyne Rolli-Derkinderen
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Contributions

M. Neunlist and L. Van Landeghem contributed to all aspects of this manuscript. M. Mahé contributed to researching data, writing and reviewing/editing the manuscript. P. Derkinderen contributed to discussion of content and reviewing/editing the manuscript. M. Rolli-Derkinderen contributed to discussion of content, writing and reviewing/editing the manuscript. S. Bruley des Varannes contributed to reviewing/editing the manuscript.

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Neunlist, M., Van Landeghem, L., Mahé, M. et al. The digestive neuronal–glial–epithelial unit: a new actor in gut health and disease. Nat Rev Gastroenterol Hepatol 10, 90–100 (2013). https://doi.org/10.1038/nrgastro.2012.221

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