2022, Vol. 43
呕吐毒素是由镰刀菌等真菌产生的次级代谢产物，又称为脱氧雪腐镰刀菌烯醇(Deoxynivalenol, DON)，属B型单端孢霉烯族毒素。DON具有天然产生和化学性质稳定等特点，广泛污染玉米、小麦、大麦等粮食作物和饲料，是食品和饲料中的主要污染性真菌毒素[1]。2014—2018年间对欧美、亚洲和南非等地区抽检的524份猪饲料成品检测结果显示，DON的检出率为88% [2]。我国是畜牧养殖和饲料生产大国，饲料中呕吐毒素污染问题十分严重，调查显示我国西北地区82.9%的小麦有DON污染，其中10%污染样品超出国标限值1000 μg/kg [3]。2019年饲料真菌毒素污染调查结果显示，饲料样品中DON的阳性检出率为92.59%，最高值达4685.7 μg/kg，麸皮样品的DON阳性检出率为100%，最高值可达6615.7 μg/kg[4]。2020年广东省动物饲料中真菌毒素污染调查结果显示，真菌毒素的检出率达75%以上，其中DON的检出率均为80%以上[5]。DON对机体有着广泛的毒性作用，能严重地损害机体免疫功能，引起急慢性中毒和疾病的发生[6]。DON急性中毒症状主要表现为人和部分动物出现腹痛、腹泻和呕吐等，长时间低剂量摄入DON会引起动物厌食和体重降低等现象[7]。DON引起人类急性中毒的参考剂量(Acute reference dose, ARfD)为8 μg/kg (以体质量计)，欧盟制定的人类每日耐受摄入量(Tolerable daily intake, TDI)是1 µg/kg (以体质量计) [8]。动物对DON的敏感程度从高到低分别为猪、大鼠、小鼠、家禽和反刍动物，猪是对DON最为敏感的动物，猪摄入50~100 μg/kg (以体质量计)的 DON即可诱发呕吐反应[9]。然而，目前关于DON的分子毒理机制尚未明确。本文主要综述了近年来DON的毒理机制和防治策略的相关研究进展，以期为防治DON对机体的毒害作用提供新的思路。
1 呕吐毒素的毒理机制研究既往的研究报道已经明确了DON具有抑制细胞蛋白质和核酸合成、诱导细胞死亡的毒理效应，DON会触发核糖体应激反应并激活核糖核酸依赖性蛋白激酶PKR和造血细胞激酶HCK，进而激活丝裂原活化蛋白激酶MAPK信号通路，促进细胞炎症反应和细胞凋亡等[10]。近年来，邓诣群课题组(以下简称我们)围绕DON的细胞毒性开展了一系列研究。肠道、肝脏和肾脏等是DON重要的作用靶器官，在肠道细胞系Caco-2、肝脏细胞系HepG2和肾脏细胞系MDCK中，我们首先明确了DON在哺乳动物细胞系中的摄取和外排是需要载体介导和能量依赖的，而P−蛋白是DON的主要外排转运体[11]。通过进一步研究发现，DON通过激活JNK/AKT/NF-κB信号通路促进P−蛋白表达和DON的外排，从而显著降低DON和其他P−蛋白底物的细胞毒性[12]。以上研究成果明确了DON在宿主细胞中吸收和外排的分子机制，有利于进一步探究DON的毒理机制。
1.1 DON诱导细胞死亡和抑制细胞增殖的毒理机制在HepG2细胞中，我们发现DON通过ATF3ΔZip2a/2b-EGR1-p21通路诱导细胞G2/M细胞周期阻滞，其中早期生长应答因子EGR1在DON诱导的细胞周期阻滞中发挥重要作用[13]。此外，DON还可诱导HepG2细胞pre-mRNA的选择性剪接，显著抑制剪接因子U2AF1和SF1的表达水平，导致RNA剪接的全局性变化，引发细胞凋亡[14]。研究还发现DON会激活内质网应激通路[15]，DON通过激活PKR磷酸化介导内质网应激的凋亡信号，改变细胞稳态[16]。DON除了诱导内质网应激以外，其氧化应激的毒理机制也备受关注。Yang等[17]发现DON也可以诱导人胃黏膜上皮细胞系GES-1产生活性氧(Reactive oxygen species, ROS)诱发氧化应激，并且通过ROS/JNK/FOXO3a介导细胞毒性作用，导致细胞线粒体DNA损伤、呼吸链功能障碍及细胞周期阻滞等，其中FOXO3a作为负调控因子在DON介导细胞毒性作用中发挥重要作用。Ndlovu等[18]研究报道，DON抑制NRF2抗氧化信号通路，从而诱导氧化应激，促进HepG2细胞毒性。我们最新研究结果发现，DON可以激活Caspase-3/GSDME通路，介导细胞焦亡，诱发小鼠肝脏炎症的发生 [19]。DON除了诱导细胞焦亡和细胞凋亡等细胞死亡方式以外，我们还发现DON可以通过抑制Wnt/β-catenin信号通路，进而抑制细胞增殖，提示β-catenin是DON的重要作用靶点[20]。王修启团队研究报道，DON急性暴露会抑制Wnt/β-catenin信号通路，影响猪肠道干细胞的活性[21]。Wnt/β-catenin信号通路是高度保守的进化通路，在调节细胞增殖、分化、迁移、遗传稳定性、凋亡和干细胞更新等方面发挥重要作用，该通路的异常活化与肿瘤的发生发展有关[22]。低剂量DON会影响肿瘤细胞系的迁移，DON通过增强细胞迁移的关键基因 TEM8启动子H3K27me3的水平来抑制TEM8的表达，从而抑制肿瘤细胞系的细胞迁移[23]。在小鼠胚胎成纤维细胞系中，DON则通过减弱PPARγ2启动子上H3K4me2和H3K4me3的富集并抑制PPARγ2表达，进而下调PPARγ2调控的脂肪形成的相关基因的表达，最终抑制脂肪形成[24]。以上研究表明，DON可以诱导细胞凋亡/焦亡及抑制细胞增殖、迁移、代谢和干细胞活性等。
1.2 DON诱发猪肠道炎症和免疫毒性的机制猪是对DON最为敏感的动物，呕吐毒素也因可引起猪的呕吐反应而得名，因此DON对猪的毒理机制也广受研究者们关注。研究表明，DON激活Caspase-12和抑制NOD2介导的防御肽产生，从而破坏断奶仔猪的肠道屏障的完整性[25]。在猪小肠上皮细胞系IPEC-J2，DON降低p-AKT/AKT、p-mTOR/mTOR和增加细胞自噬相关蛋白LC3-II的表达，该研究表明，DON可能通过抑制PI3K/AKT/mTOR信号通路激活细胞自噬，从而诱导细胞凋亡[26]。DON还可以诱导ROS产生，从而促进IPEC-J2细胞凋亡和炎症反应发生[27]。此外，DON通过p38 MAPK和JNK信号通路加剧IPEC-J2紧密连接蛋白的内吞作用和降解[28]。DON也可以通过MAPK信号通路(p38、ERK和JNK)的磷酸化诱导IPEC-J2细胞中的炎症反应[29]。Zhang等[30]发现DON通过激活p38和ERK1/2诱导IPEC-J2细胞中炎症因子的产生，p38抑制剂可减缓DON诱导产生的炎症因子IL6、TNF-α、CXCL2、CXCL8、IL12A、IL1A、CCL20、CCL4和IL15，而ERK1/2抑制剂可部分抑制IL15和IL6的产生。此外，DON通过激活NF-κB 信号通路促进IPEC-J2细胞和仔猪的肠道炎症性损伤[31-32]。新的研究表明，DON可以通过激活细胞自噬和NLRP3炎症小体加剧产毒素大肠埃希菌诱导的肠道炎症和肠道屏障损伤[33]。DON诱发的肠道炎症与机体免疫反应有着密切关系，研究表明，不同的DON暴露剂量对仔猪的免疫细胞有不同的效应，低剂量的DON可激活猪肺泡巨噬细胞TLR4/NF-κB信号，起到免疫刺激效应，而高剂量的DON可通过线粒体自噬发挥免疫抑制效应[34]。DON还会诱发机体脾脏的代谢功能紊乱[35]。脾脏是机体重要的免疫器官，DON会诱导猪原代脾脏淋巴细胞氧化应激指标ROS和丙二醛(MDA)的表达，抑制细胞抗氧化能力，随着DON的处理浓度增加，线粒体融合基因(MFN1/2和OPA1)表达水平及线粒体呼吸链复合物活性降低，细胞自噬标志物LC3和p62的mRNA水平上调，这提示 DON可能通过氧化应激抑制线粒体融合，从而促进线粒体自噬和损伤脾脏细胞[36]。
1.3 DON诱发神经毒性和生殖毒性的机制除了对肠道和免疫器官等的毒性作用，DON还具有神经毒性和生殖毒性。DON可通过Ca2+/CaM/CaMKII通路影响仔猪大脑的脂质过氧化和神经递质的表达水平，诱发神经毒性[37]。在猪海马神经细胞PHNCs中，DON也会诱导PHNCs细胞凋亡和自噬，当DON浓度增加时，LC3蛋白表达水平增加，而PI3K/AKT/mTOR通路受到抑制，这说明PI3K/AKT/mTOR信号通路在DON诱导的细胞自噬中起负调节作用[38]。在人前列腺癌细胞系PNT1A中，30和10 µmol/L的DON均可诱导细胞氧化应激、DNA损伤和细胞周期阻滞在G2/M期，其中高剂量DON诱导细胞凋亡，低剂量DON诱导细胞自噬，提示DON可能通过PI3K/AKT通路诱导细胞自噬、触发细胞凋亡[39]。此外，DON还通过Caspase-8介导的线粒体凋亡通路和MAPK信号通路等诱导PHNCs细胞凋亡[40-41]。在小鼠模型中，DON通过JNK/c-Jun信号通路加剧氧化应激介导睾丸细胞凋亡，从而影响精子的存活和活力[42]。用DON攻毒孕鼠，可观察到孕鼠的胎盘出现氧化损伤，其机制可能是DON通过激活氧化应激和NRF2核转位诱发胚胎毒性[43]。
综上所述，DON可对机体的重要组织器官产生广泛的毒性作用，其涉及的分子信号通路复杂且存在相互作用，主要包括细胞周期阻滞、氧化应激、内质网应激和线粒体自噬等。目前尚不清楚DON在机体中是否存在特异性的受体，DON发挥细胞毒性的首要靶点尚不能明确，这也阻碍了DON的特效解毒剂的研发。由于DON污染广泛且无法避免，如何干预和降低DON对畜禽的毒害作用也广受学者们关注，目前的防治策略主要有2种：一种是利用活性物质等饲料添加剂来防治和缓解呕吐毒素对畜禽的毒性效应；另外一种是从饲料源头进行防控，即通过物理、化学和生物等技术手段将受污染的饲料中的呕吐毒素进行脱毒减毒处理。
2 呕吐毒素的毒性防治研究进展目前已研究报道多种生物制剂，包括益生菌、植物活性物质、中草药和抗氧化剂等，对防治DON的毒性具有良好的效果，具有作为饲料添加剂的应用前景。生物制剂防治DON毒性的保护机制主要是缓解氧化应激和内质网应激、增强免疫力、抑制炎症和调节肠道菌群等。
由于DON暴露也会影响动物肠道菌群的平衡[44]，益生菌不仅可以调节肠道菌群的稳态[45]，而且还能调节宿主免疫系统的作用和增强肠道屏障功能[46-47]，因此，益生菌在缓解DON对机体的毒害作用方面也备受关注。有研究报道，鼠李糖乳酸杆菌Lactobacillus rhamnosus RC007能缓解DON对猪肠道外植体的促炎效应和肠道通透性的改变等，这提示鼠李糖乳酸杆菌RC007有望成为降低DON肠道毒性的益生菌[48]。基于小鼠模型，我们发现益生菌鼠李糖乳酸杆菌LGG菌株可促进肠道微生物产生丁酸，缓解DON诱发的内质网应激和肠道损伤等[15]。鼠李糖乳酸杆菌LGG菌株除了缓解DON的肠道毒性，国内其他课题组也陆续报道了LGG菌株可缓解DON诱导的仔猪肝损伤和肾损伤等，例如LGG菌株通过抑制TLR4/NF-κB信号通路来明显减轻DON引起的小鼠肝脏炎症反应[49]，此外，LGG菌株还可以通过抑制DON介导的线粒体自噬进而缓解肾脏毒性[50]。其他乳酸菌株，例如植物乳酸杆菌L. plantarum JM113菌株可通过增加肠道有益细菌的丰度减少DON对肉鸡的肠道损伤作用，增强肉鸡肠道的消化、吸收和代谢功能等[51]。此外，植物乳酸杆菌的代谢产物亦具备抗氧化功能，可以有效减少DON对猪外植体的氧化应激效应和毒性作用[52]。除了乳酸杆菌以外，德沃斯氏菌Devosia sp. ANSB714菌株也被报道能有效缓解DON对猪的生长抑制作用，可提高仔猪体重、采食量、免疫功能、抗氧化能力和肠道完整性等[53]。
植物活性物质具备天然绿色、健康安全及良好抗氧化活性等优点，是潜在的优良饲料添加剂，目前已经发现有多种植物活性物质能防治DON的毒性作用。研究表明，从猴头菇Hericium erinaceus中提取的多糖主要由葡萄糖和鼠李糖组成，该多糖具备抗氧化活性，能抑制DON诱导的氧化应激反应，抑制IPEC-J2细胞产生ROS和细胞凋亡[54]。番茄红素是主要存在于西红柿、红色蔬果中的一种类胡萝卜素，研究发现番茄红素通过KEAP1/NRF2信号通路抑制DON诱导的ROS的产生，能有效修复DON引起的肠道损伤和改善肠道屏障功能[55]。芒果苷主要来源于知母Anemarrhena asphodeloides的根茎和芒果Mangifera indica的叶等，它也能激活NRF2信号通路，抑制DON诱导的血管内皮细胞氧化损伤[56]。白藜芦醇是一种非黄酮类多酚有机化合物，在葡萄Vitis vinifera、虎杖Reynoutria japonica及花生Arachis hypogaea等植物中含量较高。白藜芦醇可激活NRF2信号通路，减少IPEC-J2细胞中ROS的产生，起到稳定线粒体膜电位和抑制细胞凋亡从而抑制DON对肠道细胞损伤的保护作用[57]。紫檀芪是白藜芦醇的二甲基化衍生物，被称为下一代白藜芦醇，它也可缓解DON对牛乳腺上皮细胞系MAC-T造成的氧化损伤和炎症效应[58]。五味子甲素是从五味子Schisandra chinensis果实中分离得到的一种木脂素化合物，五味子甲素可有效抑制DON对人肠道细胞系HT-29的细胞毒性，其保护机制可能是五味子甲素通过NRF2信号通路下调HO-1的表达而抑制DON诱导的氧化应激。此外，五味子甲素还可以通过抑制MAPK信号通路的激活而抑制细胞炎症因子的表达等[59]。
我国中草药资源丰富，部分中草药中的有效成分也被证明具有防治DON细胞毒性的效果。山奈酚是一种主要来自于山奈Kaempferia galanga根茎的黄酮类化合物，山奈酚可以增加紧密连接蛋白ZO-1和Claudin-3的表达，增强肠道屏障功能，从而减缓DON对Caco-2细胞的毒性作用[60]。绿原酸广泛存在于金银花Lonicera japonica、杜仲Eucommia folium叶等多种草本植物中，绿原酸亦通过抑制细胞凋亡和产生炎症因子等改善肠道屏障功能，缓解DON对IPEC-J2的细胞毒性作用[61]。黄连素可通过调节NF-κB/MAPK信号通路，改善DON诱导的氧化应激、炎症因子释放和肠道屏障损伤等[62]。黄芩苷通过抑制NF-κB和激活mTOR信号通路缓解DON诱导的猪肠道炎症和氧化应激损伤[63]。
研究表明，抗氧化剂、脂肪酸和褪黑素等在缓解DON的细胞毒性方面具有良好效果。硒可提高谷胱甘肽过氧化物酶活性，缓解DON对猪脾脏淋巴细胞的损伤[64]。维生素E通过抑制ROS生成、增加抗氧化酶活性和诱导NRF2相关抗氧化蛋白的表达来缓解DON对人脑微血管内皮细胞的毒性作用[65]。富勒烯可提高超氧化物歧化酶和谷胱甘肽过氧化物酶的活性，从而抑制DON诱导的氧化应激[66]。L−肌肽可以通过激活KEAP1/NRF2信号通路增强肠道干细胞的抗氧化能力，维持肠道干细胞的增殖和分化，从而防治DON对肠上皮的损伤[67]。除了抗氧化剂，我们发现丁酸钠可抑制内质网应激信号通路，缓解DON对小鼠的肠道毒理作用[15]。齐德生团队也证明丁酸钠可减轻DON对断奶仔猪肝脏和肠道的损伤作用[68]。长链n-3多不饱和脂肪酸EPA和DHA等也可抑制猪肠上皮细胞坏死信号通路，减轻DON对肠道屏障功能的破坏[69]。褪黑素是由脑松果体分泌的激素，它可通过抑制内质网应激和FOXO1的表达水平抑制DON诱导的细胞凋亡和功能障碍[70]。
3 呕吐毒素的脱毒微生物研究进展饲料中真菌毒素脱毒的方法大致可分为物理脱毒、化学脱毒和生物脱毒3类。物理脱毒方法包括物理吸附、微波、辐射、高压脉冲和挤压以及热处理等，化学脱毒方法主要通过强酸、强碱及强氧化剂改变毒素结构，将毒素转化为无毒或低毒物质。DON的物理化学性质稳定，利用传统的物理和化学脱毒方法具有局限性，比如会造成营养物质的损失、试剂残留和对环境的二次污染等[71]。生物脱毒是利用微生物或者酶制剂将真菌毒素转化为低毒甚至无毒的代谢产物，解毒效果较明显，该方法备受推崇[72]。近年来，微生物脱毒技术是饲料和食品的真菌毒素脱毒方法中最具有发展前景和潜力的脱毒方法，具有高效、低毒、特异性强、不损害营养物质等优点[73]。微生物对DON的解毒代谢途经主要有C12、13位脱环氧以及C3位氧化和C3位差向异构化等，将DON代谢转化为无毒或者低毒的产物，从而达到解毒作用。
脱环氧代谢是将DON分子的C12、13位环氧结构还原成C9、12二烯结构，形成脱环氧代谢产物DOM-1(Deepoxy-4-deoxynivalenol)，其相对于母体化合物几乎无毒[74]。Fuchs等[75]从牛的瘤胃中分离到的第1株纯培养的厌氧优杆菌属 Eubacterium BBSH797菌株可将DON脱环氧代谢为无毒代谢产物，该菌株目前已被开发成饲料添加剂进行商品化应用。此外，从鸡肠道中分离出的梭状芽孢杆菌Clostridium sp. WJ06和芽孢杆菌Bacillus sp. LS100均能将DON进行脱环氧代谢，将其添加到有DON污染的饲料中均可明显地改善猪的生长性状[76-77]。我们在鸡肠道中相继分离获得2株DON脱环氧代谢菌株伊格尔兹氏菌Eggerthella sp. DII-9和史雷克氏菌Slackia sp. D-G6，这2株菌株均可在48 h内将40~50 μg DON代谢转为DOM-1，是目前全球范围内对DON脱环氧代谢效率最高的菌株[78-79]。此外，史雷克氏菌Slackia sp. D-G6还可以将大豆异黄酮降解转化为雌马酚，雌马酚具有抗氧化和抗肿瘤等功能，提示Slackia sp. D-G6不仅具备降解DON的能力，还具备潜在的益生菌功能，具有良好的应用前景[79]。He等[80]从土壤样品中分离得到脱硫杆菌Desulfitobacterium sp. PGC-3-9，该菌能将DON进行脱环氧代谢。然而，微生物将DON进行脱环氧代谢的机制尚不清楚。
C3位氧化是将C3位的羟基氧化成酮基，形成低毒产物3-keto-DON，毒性降低至DON的1/10。Shima等[81]从土壤样品中分离到的农杆菌Agrobacterium-Rhizobium E3-39菌株能将DON代谢为3-keto-DON。赵丽红课题组从中国渤海的海水样品中分离到耐盐海杆菌Pelagibacterium halotolerans ANSP101菌株，该菌株可将 DON 转化为3-keto-DON[82]，并且近期研究发现是ANSP101菌株的脱氢酶DDH将DON氧化为3-keto-DON[83]。
DON的C3位差向异构化被证明是由2步反应组成，第1步是DON的C3位羟基发生氧化脱氢反应形成酮基，使DON(R构象)转化为3-keto-DON；第2步是3-keto-DON的C3位酮基被还原成S构象的羟基，形成无毒的3-epi-DON[84]。He等[85]从苜蓿Medicago sativa的土壤样品中筛选获得1株可将DON代谢为3-epi-DON的德沃斯氏菌Devosia sp. 17-2-E-8。Devosia sp. 17-2-E-8对DON异构化需要2步催化反应，第1步是由吡咯喹啉醌依赖的脱氢酶DepA将DON氧化为3-keto-DON，第2步是由还原型辅酶Ⅱ(NADPH)依赖的脱氢酶DepB催化3-keto-DON还原为3-epi-DON[86-87]。此外，廖玉才课题组也在土壤样品中分离得到2株可降解DON的菌株，分别为鞘氨醇单胞菌Sphingomonas sp. S3-4和德沃斯氏菌Devosia sp. D6-9，其中Devosia sp. D6-9菌株也是先通过脱氢酶QDDH将DON氧化为3-keto-DON，再由NADPH依赖的醛酮还原酶AKR13B2和AKR6D1将3-keto-DON转化为3-epi-DON[88]，而Sphingomonas sp. S3-4菌株则是通过醛酮还原酶超家族AKR18A1酶将DON催化为3-keto-DON，3-keto-DON 进一步被未知的酶转化为3-epi-DON [89]。除了德沃斯氏菌以外，Paradevosia shaoguanensis DDB001和类诺卡氏菌Nocardioides sp. WSN05-2菌株均能将 DON 转化为3-epi-DON[90-91]，含有不动杆菌属Acinetobacter、里德拜特氏菌Leadbetterella和出芽菌属Gemmata的混合培养微生物也可将 DON转化为3-epi-DON[92]。类诺卡氏菌Nocardioides sp. ZHH-013也能将DON转化为3-keto-DON和3-epi-DON，其中3-keto-DON是转化为3-epi-DON的必要中间产物，并且Nocardioides sp. ZHH-013还能代谢3-epi-DON[93]。然而，关于这些菌株中参与代谢DON的关键酶或者基因等的研究鲜见报道。
4 总结与展望真菌毒素可在食物链的各个环节污染农作物、饲料原料和饲料等，我国真菌毒素污染的严重程度远超过世界平均水平，其中DON是污染最普遍的真菌毒素之一，其毒性机理和代谢转化一直是农业领域和食品领域的热门研究课题。尽管当前的研究能够阐释部分DON的细胞毒理机制，包括核糖体应激、氧化应激、内质网应激以及复杂交互的分子信号转导通路等，但是关于DON发挥细胞毒性的首要靶点尚不能明确，以及DON诱导猪等动物发生呕吐和厌食等中毒病症的发生机制也尚未阐明。未来的研究重点仍需要阐明DON的分子毒理机制以及细胞毒理与动物中毒病症发生机制的内在联系，研发治疗DON中毒病症的特效解毒剂。益生菌、植物活性物质、中草药和抗氧化剂等生物制剂可缓解DON的毒性作用，具有良好的应用前景，但是仍需进一步评估这些生物制剂作为饲料添加剂的安全性、有效性和可行性等。
关于DON的微生物脱毒机理，虽然目前已经发现并确定参与DON的C3位氧化和异构化的酶，但是当前鉴定和挖掘的酶资源仍然十分有限，另外，C12、13位的环氧基是单端孢霉烯族毒素的活性基团，DON的C3位氧化和异构化代谢产物中的环氧基尚未被破坏，在某些条件下是否会对机体产生不利的影响还不得而知，且DON代谢转化为3-keto-DON和3-epi-DON的过程可能是可逆的，这些因素都在一定程度上限制了DON的C3位氧化和异构化的微生物和酶制剂等的开发和应用。利用微生物或酶制剂将DON脱环氧代谢是最具有应用前景的生物脱毒方式，目前商品化脱环氧代谢微生物BBSH797是国外的专利产品，我国作为畜牧养殖和饲料生产大国，急需开发有自主产权可商品化的脱环氧代谢菌株和酶制剂等。虽然已经有多株菌株被报道具有脱环氧代谢DON的功能，但是可纯培养的菌株数量仍然有限，对其脱环氧代谢的关键基因和机制尚未阐明，因此，还需要进一步研究DON的脱环氧代谢机制。目前较为可行的方案是筛选降解能力强的多种脱环氧代谢菌株，扩充微生物库资源，通过比较基因组学和转录组分析等多种技术方法筛选鉴定脱环氧代谢的关键基因，评价和优化脱毒微生物或活性酶脱毒效果等，使其能应用于食品和饲料工业的生产实践。综上所述，开发微生物或酶制剂进行饲料脱毒，从源头控制畜禽摄入真菌毒素，寻找治疗畜禽真菌毒素中毒病的有效药物，阻断真菌毒素对畜禽的机体损伤，是真菌毒素研究领域的重点和难点。
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