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

霉菌毒素是霉菌的有毒代谢产物，通常污染世界各地的谷物和牲畜饲料作物。霉菌毒素的消费导致畜牧业的生产力和健康下降，造成重大经济损失。有超过500种不同类别的霉菌毒素，其中许多具有未知的作用机制（MOA），并且它们经常作为混合污染物被发现。在牲畜饲料中添加霉菌毒素结合剂（即奥特奇的酵母基Mycosorb A+®）是降低霉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。奥特奇继续修改其'酵母为基础的产品，希望提高和多样化的霉菌毒素结合效力，这些下一代的结合剂需要进行评估。当测试真菌毒素在不同物种中的毒性以及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系（BoMAC）用于进行此类研究的实用性;然而，单独的BoMAC在形态学上不能反映大多数真菌毒素暴露发生的肠屏障。使用肠上皮细胞（IEC）或甚至更好的共培养IEC +巨噬细胞（IEC+BoMAC）进行体外暴露研究在生理学上更具相关性。拟议的研究将使用牛IEC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有效性。

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.