Penicillium and Fusarium mycotoxin assessment using bovine intestinal epithelial cells (IEC) and co-cultured IEC + macrophages, and remediation with yeast mycotoxin binders

霉菌毒素是来自霉菌的有毒代谢物，通常污染世界各地的谷物和牲畜饲料作物。由于生产力和健康下降，真菌毒素的消费给畜牧业造成了巨大的经济损失。真菌毒素有500多种不同类别，其中许多具有未知的作用机制（MOA），它们经常被发现为混合污染物。在牲畜饲料中添加霉菌毒素粘合剂（即Alltech的酵母基Mycosorb A+®）是降低真菌中毒风险的重要补救策略，因为它们可以降低某些霉菌毒素的生物利用度，从而减少肠道上皮的吸收。Alltech继续改进其基于酵母的产品，希望改善和多样化霉菌毒素结合效果，这些下一代粘合剂需要进行评估。在测试不同物种真菌毒素的毒性以及Mycosorb A+®和新一代变体降低真菌毒素生物利用度的功效时，体外研究对于初始筛选至关重要。我们已经证明了牛巨噬细胞细胞系（BoMAC）用于开展此类研究的实用性；然而，单靠BoMACs并不能从形态学上反映大多数霉菌毒素暴露发生的肠道屏障。在生理上，使用肠上皮细胞（IEC）进行体外暴露研究更有意义，甚至更好的是使用共培养的IEC+巨噬细胞（IEC+BoMAC）。该研究将使用牛IECs和共培养的IEC+BoMAC来探索霉菌毒素暴露对肠道屏障的影响，并评估霉菌毒素结合剂Mycosorb A+®或新一代变体降低霉菌毒素生物利用度的效果。

Mycotoxins are toxic metabolites from mold that commonly contaminate cereal and livestock feed crops around the world. The consumption of mycotoxins contributes to substantial economic losses to the livestock industry due to reduced productivity and health. There are over 500 different classes of mycotoxins, many of which have unknown mechanisms of action (MOA), and they are frequently found as mixture contaminants. Adding mycotoxin binders to livestock feeds (i.e. Alltech's yeast-based Mycosorb A+®) is an important remediation strategy for reducing risk of mycotoxicosis, since they can reduce bioavailability of certain mycotoxins, which reduces absorption across the gut epithelium. Alltech continues to modify its' yeast-based product with the hope of improving and diversifying mycotoxin binding efficacy, and these next generation binders need to be evaluated. When testing the toxicity of mycotoxins in different species, and the efficacy of Mycosorb A+® and new generation variants for reducing mycotoxin bioavailability, in vitro studies are critical for initial screening. We have demonstrated the utility of a bovine macrophage cell line (BoMAC) for carrying out such studies; however, BoMACs alone do not morphologically reflect the intestinal barrier where most mycotoxin exposure occurs. It is physiologically more relevant to carry out in vitro exposure studies using intestinal epithelial cells (IEC), or even better, co-cultured IEC + macrophages (IEC+BoMAC). The proposed study will use bovine IECs and co-cultured IEC+BoMAC to explore the impact of mycotoxin exposure on the intestinal barrier, and to assess the efficacy of the mycotoxin binder Mycosorb A+® or new generation variants for reducing mycotoxin bioavailability.