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Real-time Measurement of Epithelial Barrier Permeability in Human Intestinal Organoids
Published on: December 18, 2017
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High-Throughput Screen Identifies Host and Microbiota Regulators of Intestinal Barrier Function.
Inna Grosheva1, Danping Zheng2, Maayan Levy3
1Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel; Immunology Department, Weizmann Institute of Science, Rehovot, Israel.
Gastroenterology
|July 13, 2020
Summary
Researchers identified molecules that disrupt or stabilize the intestinal epithelial barrier. Certain molecules, like putrescine, worsen colon inflammation, while others, like taurine, can prevent it, offering potential therapeutic strategies.
Area of Science:
- Gastroenterology
- Immunology
- Molecular Biology
Background:
- The intestinal barrier is crucial for preventing harmful microbes and antigens from entering the body.
- Breaches in this barrier can lead to altered gut microbiota, immune dysfunction, and metabolic changes.
Purpose of the Study:
- To identify molecules that disrupt or support the intestinal epithelial barrier.
- To investigate the effects of these molecules on intestinal inflammation in mouse models.
Main Methods:
- A high-throughput screen identified molecules affecting epithelial tight junction (TJ) morphology.
- Tested TJ stabilizers and identified disruptors/stabilizers were administered to mice with induced colitis or Citrobacter rodentium infection.
- Analyzed colon tissues using histology, fluorescence microscopy, and RNA sequencing.
Main Results:
- Numerous compounds altering TJ integrity were identified.
- Putrescine disrupted TJ integrity, exacerbated colon inflammation, increased gut permeability, and reduced survival in mice.
- Putrescine increased bacterial attachment and inflammatory cytokines, while taurine co-administration blocked these effects.
Conclusions:
- Identified molecules that modulate intestinal epithelial TJs and barrier function.
- These agents could be developed for treating inflammatory disorders or avoided to prevent inflammation.
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