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.

中文翻译：

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丁酸盐可降低猪空肠类器官来源的细胞单层中食源性霉菌毒素脱氧雪腐镰刀菌烯醇诱导的上皮屏障功能障碍。


镰刀菌属产生的食源性霉菌毒素脱氧雪腐镰刀菌烯醇 （DON） 通过破坏肠道屏障威胁动物和人类健康。靶向肠道微生物群及其产物似乎是减轻 DON 肠道毒性的一种有前途的策略。在这项研究中，我们研究了细菌代谢物丁酸盐是否可以减轻 DON 诱导的上皮屏障破坏。我们使用了源自猪空肠类器官的细胞单层模型，可以再现肠上皮细胞的复杂性。我们的结果表明，DON 剂量依赖性地破坏了上皮屏障完整性，减少了上皮分化，并改变了先天免疫防御。丁酸盐减弱了 DON 诱导的细胞旁通透性增加。丁酸盐还防止了由茴香霉素（一种类似于 DON 的核糖体抑制剂）引发的上皮屏障功能障碍。此外，丁酸盐部分抵消了 DON 对紧密连接 （TJP1、OCLN）、先天上皮防御 （PTGS2、CD14、TLR4、TLR5） 和吸收细胞功能 （CA2、VIL1、NHE3、CFTR） 的影响。相比之下，丁酸盐并不能阻止 DON 对线粒体代谢、增殖和杯状细胞功能的毒性作用。综上所述，我们的结果表明，细菌代谢物丁酸盐能够减少 DON 诱导的上皮屏障破坏。