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Nat Rev Gastroenterol Hepatol. 2017 Jan;14(1):9-21. doi: 10.1038/nrgastro.2016.169. Epub 2016 Nov 16.

The intestinal epithelial barrier: a therapeutic target?

Author information

1
Department of Pathology, The University of Chicago, 5841 South Maryland, Chicago, Illinois 60637, USA.
2
Departments of Pathology and Medicine (Gastroenterology), Brigham and Women's Hospital and Harvard Medical School, 20 Shattuck Street, Thorn 1428, Boston, Massachusetts 02115, USA.

Abstract

A fundamental function of the intestinal epithelium is to act as a barrier that limits interactions between luminal contents such as the intestinal microbiota, the underlying immune system and the remainder of the body, while supporting vectorial transport of nutrients, water and waste products. Epithelial barrier function requires a contiguous layer of cells as well as the junctions that seal the paracellular space between epithelial cells. Compromised intestinal barrier function has been associated with a number of disease states, both intestinal and systemic. Unfortunately, most current clinical data are correlative, making it difficult to separate cause from effect in interpreting the importance of barrier loss. Some data from experimental animal models suggest that compromised epithelial integrity might have a pathogenic role in specific gastrointestinal diseases, but no FDA-approved agents that target the epithelial barrier are presently available. To develop such therapies, a deeper understanding of both disease pathogenesis and mechanisms of barrier regulation must be reached. Here, we review and discuss mechanisms of intestinal barrier loss and the role of intestinal epithelial barrier function in pathogenesis of both intestinal and systemic diseases. We conclude with a discussion of potential strategies to restore the epithelial barrier.

PMID:
27848962
PMCID:
PMC5554468
DOI:
10.1038/nrgastro.2016.169
[Indexed for MEDLINE]
Free PMC Article

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