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. 2024 Jan-Dec;16(1):2430424.
doi: 10.1080/19490976.2024.2430424. Epub 2024 Nov 21.

Butyrate reduces epithelial barrier dysfunction induced by the foodborne mycotoxin deoxynivalenol in cell monolayers derived from pig jejunum organoids

Julie Alberge  1 , Eloïse Mussard  1   2 , Carine Al-Ayoubi  3 , Corinne Lencina  1 , Christelle Marrauld  1 , Laurent Cauquil  1 , Caroline S Achard  2 , Ivan Mateos  1   2   4 , Imourana Alassane-Kpembi  3   5 , Isabelle P Oswald  3 , Laura Soler  3 , Sylvie Combes  1 , Martin Beaumont  1
Affiliations

Butyrate reduces epithelial barrier dysfunction induced by the foodborne mycotoxin deoxynivalenol in cell monolayers derived from pig jejunum organoids

Julie Alberge et al. Gut Microbes. 2024 Jan-Dec.

Abstract

The foodborne mycotoxin deoxynivalenol (DON) produced by Fusarium species threats animal and human health through disruption of the intestinal barrier. Targeting the gut microbiota and its products appears as a promising strategy to mitigate DON intestinal toxicity. In this study, we investigated whether the bacterial metabolite butyrate could alleviate epithelial barrier disruption induced by DON. We used a model of cell monolayers derived from porcine jejunum organoids allowing to reproduce the cellular complexity of the intestinal epithelium. Our results show that DON dose-dependently disrupted the epithelial barrier integrity, reduced epithelial differentiation, and altered innate immune defenses. Butyrate attenuated the DON-induced increase in paracellular permeability. Butyrate also prevented epithelial barrier dysfunction triggered by anisomycin, a ribosome inhibitor like DON. Moreover, butyrate partially counteracted the effects of DON on tight junctions (TJP1, OCLN), innate epithelial defenses (PTGS2, CD14, TLR4, TLR5), and absorptive cell functions (CA2, VIL1, NHE3, CFTR). In contrast, butyrate did not prevent the toxic effects of DON on mitochondrial metabolism, proliferation and goblet cell functions. Taken together, our results demonstrate that the bacterial metabolite butyrate is able to reduce DON-induced epithelial barrier disruption.

Keywords: Gut microbiota; enteroids; epithelium; metabolites; permeability; toxin.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
Deoxynivalenol dose-dependently disrupts the epithelial barrier integrity.
Figure 2.
Figure 2.
Deoxynivalenol dose-dependently alters the expression of genes involved in epithelial proliferation and differentiation.
Figure 3.
Figure 3.
Deoxynivalenol dose-dependently alters the expression of genes involved in epithelial innate immunity.
Figure 4.
Figure 4.
Butyrate alleviates deoxynivalenol-induced disruption of epithelial barrier integrity.
Figure 5.
Figure 5.
Butyrate alleviates the disruption of epithelial barrier integrity induced by the ribotoxin anisomycin.
Figure 6.
Figure 6.
Butyrate reduces the disruption of tight junctions induced by deoxynivalenol.
Figure 7.
Figure 7.
Butyrate, but not deoxynivalenol, is transported across cell monolayers derived from pig intestinal organoids.
Figure 8.
Figure 8.
Butyrate does not prevent the effects of DON on epithelial proliferation.
Figure 9.
Figure 9.
Butyrate alleviates the effects of DON on epithelial differentiation.
Figure 10.
Figure 10.
Butyrate reduces the don-induced disruption of epithelial defenses.
Figure 11.
Figure 11.
Inhibition of histone deacetylases reproduces some of the effects of butyrate on gene expression.
Figure 12.
Figure 12.
The effect of DON on the gut microbiota is moderate and transient.
See this image and copyright information in PMC

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