Mycotoxin Deoxynivalenol Has Different Impacts on Intestinal Barrier and Stem Cells by Its Route of Exposure

Hikaru Hanyu1, Yuki Yokoi2, Kiminori Nakamura2

  • 1Department of Nutritional Science, Faculty of Applied Bioscience, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502, Japan.

Toxins
|September 29, 2020
PubMed

Insights

Basolateral exposure to deoxynivalenol (DON) significantly damages intestinal barrier function and stem cells more than luminal exposure. This study highlights route-dependent toxicity of DON on intestinal health.

Area of Science:

  • Gastroenterology
  • Toxicology
  • Cell Biology

Background:

  • The impact of deoxynivalenol (DON) on intestinal health varies with exposure route.
  • Understanding DON's effects on intestinal barrier and stem cells is crucial for assessing its toxicity.

Purpose of the Study:

  • To investigate the differential toxic effects of deoxynivalenol (DON) on intestinal barrier function and stem cells based on exposure route (luminal vs. basolateral).

Main Methods:

  • Utilized three-dimensional mouse intestinal organoids (enteroids) for controlled luminal and basolateral DON exposure.
  • Assessed intestinal barrier integrity using fluorescein-labeled dextran influx and immunofluorescence for tight junction proteins (E-cadherin, claudin, ZO-1, occludin).
  • Evaluated stem cell effects using Lgr5-EGFP reporter mice and EdU incorporation assays to measure stem cell count and proliferation.

Main Results:

  • Basolateral DON exposure (1 µM) significantly disrupted intestinal barrier function and epithelial integrity compared to luminal exposure.
  • Only basolateral DON exposure suppressed leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5)+ stem cell counts and proliferative cell ratios.
  • RNA sequencing revealed distinct gene expression profiles following basolateral versus luminal DON exposure.

Conclusions:

  • Basolateral DON exposure poses a greater threat to intestinal barrier integrity and stem cell populations than luminal exposure.
  • This study is the first to demonstrate route-dependent differential impacts of DON on intestinal stem cells.
  • Findings underscore the importance of considering the route of exposure when evaluating DON's gastrointestinal toxicity.

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