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Updated: Jun 24, 2026
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Functional Assessment of Intestinal Permeability and Neutrophil Transepithelial Migration in Mice using a Standardized Intestinal Loop Model
Published on: February 11, 2021
Systemic inflammation increases intestinal permeability during experimental human endotoxemia
Falco Hietbrink1, Marc G H Besselink, Willem Renooij
1Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands. F.Hietbrink@umcutrecht.nl
Shock (Augusta, Ga.)
|March 20, 2009
Summary
Systemic inflammation increases intestinal permeability in humans. This study shows increased recovery of polyethylene glycols (PEGs) during experimental endotoxemia, indicating a "leaky gut" due to inflammation, not cell damage.
Area of Science:
- Gastroenterology
- Immunology
- Critical Care Medicine
Background:
- The gut's role in sepsis is recognized, but the link between systemic inflammation and intestinal permeability in humans remains unclear.
- Understanding this relationship is crucial for managing sepsis and related inflammatory conditions.
Purpose of the Study:
- To investigate the impact of experimental endotoxemia on human intestinal permeability.
- To determine if systemic inflammation or enterocyte damage is the primary driver of increased intestinal permeability.
Main Methods:
- 14 healthy subjects underwent experimental endotoxemia induced by Escherichia coli lipopolysaccharide (LPS).
- Intestinal permeability was assessed using polyethylene glycol (PEG) recovery (PEG 1,500 and 4,000).
- Enterocyte damage was measured via intestinal fatty acid-binding protein (I-FABP) excretion.
Main Results:
- Endotoxemia triggered a significant inflammatory response.
- Urinary recovery of PEG 1,500 and 4,000 increased significantly, indicating heightened intestinal permeability.
- I-FABP excretion remained unaffected, ruling out significant enterocyte damage as the cause.
- Increased serum IL-10 levels correlated with elevated PEG 1,500 recovery.
Conclusions:
- Systemic inflammation directly leads to increased intestinal permeability in humans.
- The observed increase in permeability is likely due to inflammation-induced paracellular changes, not ischemia-related enterocyte damage.
- This finding clarifies a key mechanism in the gut-sepsis axis.
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