Intestinal Permeability Defects: Is It Time to Treat?

Odenwald, Matthew A.; Turner, Jerrold R.

doi:10.1016/j.cgh.2013.07.001

Cited by 366Gastrointestinal motility and disordersBarrier Structure and Function StudiesInflammatory Bowel Disease

Intestinal Permeability Defects: Is It Time to Treat?

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Odenwald, Matthew A., Turner, Jerrold R.·2013·Clinical Gastroenterology and Hepatology

DOI 10.1016/j.cgh.2013.07.001PMC PMC3758766

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Abstract

An essential role of the intestinal epithelium is to separate luminal contents from the interstitium, a function primarily determined by the integrity of the epithelium and the tight junction that seals the paracellular space. Intestinal tight junctions are selectively permeable, and intestinal permeability can be increased physiologically in response to luminal nutrients or pathologically by mucosal immune cells and cytokines, the enteric nervous system, and pathogens. Compromised intestinal barrier function is associated with an array of clinical conditions, both intestinal and systemic. Although most available data are correlative, some studies support a model where cycles of increased intestinal permeability, intestinal immune activation, and subsequent immune-mediated barrier loss contribute to disease progression. This model is applicable to intestinal and systemic diseases. However, it has not been proven, and both mechanistic and therapeutic studies are ongoing. Nevertheless, the correlation between increased intestinal permeability and disease has caught the attention of the public, leading to a rise in popularity of the diagnosis of "leaky gut syndrome," which encompasses a range of systemic disorders. Proponents claim that barrier restoration will cure underlying disease, but this has not been demonstrated in clinical trials. Moreover, human and mouse studies show that intestinal barrier loss alone is insufficient to initiate disease. It is therefore uncertain whether increased permeability in these patients is a cause or effect of the underlying disorder. Although drug targets that may mediate barrier restoration have been proposed, none have been proven effective. As such, current treatments for barrier dysfunction should target the underlying disease.

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Leaky gut syndrome allows microbial components like LPS, toxic metabolites, and inflammatory agents to enter the bloodstream.
“LGS allows microbial components like lipopolysaccharide (LPS), toxic metabolites, and inflammatory agents to enter the bloodstream [44,45].”
From The Gut–Brain–Microbiota Connection and Its Role in Autism Spectrum Disorders (2025) · cites this paper as [44]
Dysbiosis can compromise the intestinal barrier, leading to increased intestinal permeability, commonly referred to as leaky gut syndrome.
“Dysbiosis can compromise this barrier, leading to increased intestinal permeability, commonly referred to as “leaky gut” syndrome (LGS).”
From The Gut–Brain–Microbiota Connection and Its Role in Autism Spectrum Disorders (2025) · cites this paper as [44]

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[18]Jodal M Fihn B-M Sjøqvist A Effect of glucose on passive transport of extracellular probes across the rat small intestinal epithelium in vivo Gastroenterology 1994 107 A241 11040189
[37]May GR Sutherland LM Meddings JB Lactulose/mannitol permeability is increased in relatives of patients with Crohn’s disease Gastroenterology 1992 102 A934 8500719

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Self-citation

Authors: Odenwald, M. A., & Turner, J. R.
Affiliations: University of Chicago (US)
Corresponding author: Turner, Jerrold R.
ORCID: Odenwald, Matthew A.
Turner, Jerrold R.
Venue: Clinical Gastroenterology and Hepatology
Publisher: Elsevier BV
Published: 2013-09
Volume: 11
Issue: 9
Pages: 1075-1083
ISSN: 1542-3565 (ISSN-L)
DOI: 10.1016/j.cgh.2013.07.001
PMC: PMC3758766
OpenAlex: W2014385625
Cited by: 366
References: 111
Citations by year: 2026: 15 · 2025: 27 · 2024: 35 · 2023: 42 · 2022: 32 · 2021: 38 · 2020: 41 · 2019: 30 · 2018: 13 · 2017: 23 · 2016: 29 · 2015: 17 · 2014: 23
FWCI: 3.66
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (am, 313 d)
Locations: Clinical Gastroenterology and Hepatology (acceptedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: Crohn's and Colitis Foundation (252879)
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK068271, R01DK061931)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD007009)
Topics: Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
Keywords: intestinal permeability, leaky gut, intestinal barrier function, tight junctions, intestinal epithelium, cytokines, enteric nervous system, systemic disease
MeSH terms: Gastrointestinal Diseases, Humans, Intestinal Mucosa, Permeability

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Intestinal Permeability Defects: Is It Time to Treat?

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