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

使用牛肠上皮细胞 (IEC) 和共培养的 IEC 巨噬细胞评估青霉菌和镰刀菌霉菌毒素，并使用酵母霉菌毒素结合剂进行修复

• 批准号: 532378-2018
• 负责人: Karrow, Niel
• 金额: $ 9.25万
• 依托单位: University of Guelph
• 依托单位国家: 加拿大
• 项目类别: Collaborative Research and Development Grants
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=693410
• 关键词: Penicillium; Fusarium; mycotoxin; assessment; using

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.

霉菌毒素是霉菌的有毒代谢物，通常污染世界各地的谷物和牲畜饲料作物。由于生产力和健康的降低，霉菌毒素的消耗给畜牧业造成了巨大的经济损失。霉菌毒素有 500 多种不同类别，其中许多具有未知的作用机制 (MOA)，并且经常以混合物污染物的形式被发现。在牲畜饲料中添加霉菌毒素结合剂（即奥特奇基于酵母的 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。奥特奇继续改进其基于酵母的产品，希望提高霉菌毒素结合功效并使之多样化，并且需要对这些下一代结合剂进行评估。当测试不同物种中霉菌毒素的毒性以及 Mycosorb A+® 和新一代变体降低霉菌毒素生物利用度的功效时，体外研究对于初步筛选至关重要。我们已经证明了牛巨噬细胞系（BoMAC）在进行此类研究中的实用性；然而，BoMAC 本身并不能在形态上反映大多数霉菌毒素暴露发生的肠道屏障。使用肠上皮细胞 (IEC) 或更佳的共培养 IEC + 巨噬细胞 (IEC+BoMAC) 进行体外暴露研究在生理上更具相关性。拟议的研究将使用牛 IEC 和共培养 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功效。