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

Abstract

The different effects of deoxynivalenol (DON) on intestinal barrier and stem cells by its route of exposure remain less known. We explored the toxic effects of DON on intestinal barrier functions and stem cells after DON microinjection (luminal exposure) or addition to a culture medium (basolateral exposure) using three-dimensional mouse intestinal organoids (enteroids). The influx test using fluorescein-labeled dextran showed that basolateral DON exposure (1 micromolar (µM) disrupted intestinal barrier functions in enteroids compared with luminal DON exposure at the same concentration. Moreover, an immunofluorescence experiment of intestinal epithelial proteins, such as E-cadherin, claudin, zonula occludens-1 (ZO-1), and occludin, exhibited that only basolateral DON exposure broke down intestinal epithelial integrity. A time-lapse analysis using enteroids from leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5)-enhanced green fluorescence protein (EGFP) transgenic mice and 5-ethynyl-2-deoxyuridine (EdU) assay indicated that only the basolateral DON exposure, but not luminal DON exposure, suppressed Lgr5+ stem cell count and proliferative cell ratio, respectively. These results revealed that basolateral DON exposure has larger impacts on intestinal barrier function and stem cells than luminal DON exposure. This is the first report that DON had different impacts on intestinal stem cells depending on the administration route. In addition, RNA sequencing analysis showed different expression of genes among enteroids after basolateral and luminal DON exposure.

Intestinal Barrier, Claudins and Mycotoxins

“…Basolateral DON exposition caused inhibited intestinal stem cell activity through the Wnt/β-catenin pathway [196]. Based on this study, Hikaru Hanyu et al decided to go one step further, demonstrating that basolateral exposure was more toxic than luminal DON exposure in terms of intestinal barrier functions and stem cells [197]. It is worth mentioning that DON toxicity observed in vitro and in vivo might be different, possibly due to biological barrier function.…”

Combinatory Exposure to Urolithin A, Alternariol, and Deoxynivalenol Affects Colon Cancer Metabolism and Epithelial Barrier Integrity in vitro

“…Altered intestinal epithelial structure may impact the route and extent of absorption or passage through the intestinal lineage of exogenous as well as endogenous chemicals (74). A recent in vitro study also suggested basolateral exposure to low concentrations of DON to disrupt epithelial tight junction proteins and further barrier functionality of enteroids (103). This highlights the importance of investigations on cellular uptake and efflux of foodborne substances.…”

The Effect of 42-Day Exposure to a Low Deoxynivalenol Dose on the Immunohistochemical Expression of Intestinal ERs and the Activation of CYP1A1 and GSTP1 Genes in the Large Intestine of Pre-pubertal Gilts

“…The presence of a ketone group at position C8 is characteristic of B trichothecenes. Deoxynivalenol also contains an epoxide group which enables the mycotoxin to bind to a large number of eukaryotic ribosome subunits and disrupt the activity of peptide transferase, thus compromising the elongation or shortening of peptide chains ( 7 ). Deoxynivalenol affects the cellular transport rate and enzyme metabolism in the cytoplasm ( 8 ), it leads to changes in affinity for active binding sites and disrupts protein synthesis ( 2 ).…”