The intestinal epithelial barrier: A therapeutic target?

By Matthew A. Odenwald, J. Turner. Nature Reviews Gastroenterology &Hepatology, 2016

1,094 citations recorded by the source corpus.

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.

Subfields: Molecular Biology, Neurology, Surgery

View Paper: https://www.semanticscholar.org/paper/cd466bb4253591f525af507a710db7d95601b8e9

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In Molecular Biology

1. F. Powrie
2. Loris Riccardo Lopetuso

Citations in the corpus

• Cytokine Networks in the Pathophysiology of Inflammatory Bowel Disease. (2019, background): “tolerance to commensal microbes and diet with efficient defense against pathogens and damage (Odenwald and Turner, 2017).”
• Intestinal barrier and gut microbiota: Shaping our immune responses throughout life (2017, background): “ever sustained inflammation or infections can lead to dysregulation in the expression of adhesion molecules, leading to barrier breach and entry of microbes.(1,6)”
• Gut microbiota, intestinal permeability, and systemic inflammation: a narrative review (2023, background): “Due to its action on intestinal permeability, it had been proposed as a treatment for IBDs [77].”
• Intestinal Barrier Dysfunction, LPS Translocation, and Disease Development (2020, background): “IL-13 induces the disruption of barrier function via upregulation of claudin-2 expression in cultured epithelial cell monolayers [94], and whether targeted inhibition of IL-13 or claudin-2 will be beneficial and without significant effects on gut function is yet to be examined [95].”