“后抗生素”时代欧美饲料之解决方案

1、The European and American Feed Solutions in the Post-Antibiotics Era后抗生素后抗生素时代欧美饲料之解决方案时代欧美饲料之解决方案Dr. Tobias Steiner 托比斯托比斯斯坦纳博士斯坦纳博士Phytobiotics GmbH, Eltville 德国菲托百傲饲料添加剂有限公司德国菲托百傲饲料添加剂有限公司2Post-AGP strategies “后抗生素后抗生素”战略战略Isoquinoline alkaloids 异喹啉生物碱Mode of action 作用机理Efficacy in pigs 对猪的作用Conc

2、lusion 结论3Antibiotics under Pressure in the US美国面临抗生素压力美国泰森食品、好市多、麦当劳、普渡食品将逐步停用抗生素鸡肉！4/2/20224DateLegislationAction1969Swann Report recommends that use of AGPs should be restricted.1986Sweden banned all antibiotics for growth promotion.1993Initial report on the isolation of vancomycin (glycopeptides

3、) resistant enterococci, which showed cross-resistance with avoparcin, a glycopeptide antibiotic used only as a AGP in animals, published (Bates et al., 1993)1997Occurrence of glycopeptide-resistant enterococci in food animals associated with use avoparcin (glycopeptides antibiotic) in Europe (Bager

4、 et al., 1997)01/199797/6/ECAvoparcin as AGP banned Glycopeptide03/199898/19/ECRonidazole banned from use in turkeys Immidazol derivates12/1998EC 2821/98Tylosin, virginiamycin, bacitracin zinc & spiramycin banned from use as AGPs12/1998EC 2788/98Carbadox & Olaquinadox banned from use as AGPs

5、01/2006EC 1831/2003 All AGPs banned - exception: Coccidiostats & histomonostatsAGP Ban in Europe 欧洲禁抗历程January 1, 2006Removal of AGPsEU Regulation No. 1831/20034/2/20225Reduced Use of Antibiotics in the Netherlands荷兰减少抗生素使用National target: -50% from 2009-2013国家国家2009-2013的目标的目标是减少是减少50%Dutch Min

6、istry of Economic Affairs, 2014Sales of therapeutic antibiotics in tons of active substance 治疗用抗生素成吨销售治疗用抗生素成吨销售 (Source: FIDIN)4/2/20226Post-AGP Strategies “后抗生素”战略结论：结论：衡量衡量一种一种抗生抗生素替素替代产代产品是品是否有否有效的效的标准标准是看是看其能其能否抗否抗炎！炎！4/2/2022Inflammatory processes cost up to 30% of energy and nutrients. 炎症消耗炎症

7、消耗30%能量能量7Healthy100%OutcomeImmune responseInflammationOutcome70%Challenged/diseaseMinimizing this portion through isoquinoline alkaloids异喹啉生物碱能减少这部分损失异喹啉生物碱能减少这部分损失30%Inflammation is costly to Performance 炎症影响生产性能Causes of Intestinal Inflammation 肠道炎症产生原因Bacteria 细菌Parasites寄生虫Feed 饲料 Healthy健康肠道In

8、flammation发炎肠道Viruses病毒Toxins 毒素4/2/202299Consequences of Intestinal Inflammation肠道发炎后果Intestinal inflammation肠道炎症Destruction of mucosa黏膜受损Absorption of nutrients 营养吸收Undigested nutrients未消化的营养物质Bacterial overgrowth & toxin levels细菌过度产生&毒素Diarrhea & ongoing inflammation腹泻&继发炎症4/2/202

9、210Post-AGP Strategies “后抗生素”战略Antibiotic 抗生素抗生素(Class)Phagocyte function inhibition吞噬细胞功能的抑制作吞噬细胞功能的抑制作用用AGP use, past or present促生长抗生素的使用，过促生长抗生素的使用，过去或现在去或现在Chloramphenicol 氯霉素NoNoBeta-lactams -内酰胺Limited 有限有限Limited 有限有限Cyclines 四环素YesYesQuinolones 喹诺酮类NoNoMacrolides 大环内酯类YesYesStreptogramin 链霉杀

10、阳菌素YesYesIsoquinoline alkaloids 异喹啉生物碱YesYesNiewold, 2007 11Post-AGP strategiesIsoquinoline alkaloids 异喹啉生物碱异喹啉生物碱Mode of actionEfficacy in pigsConclusion12AGP-Alternatives 促生长抗生素-替代产品Isoquinoline alkaloids异喹啉生物碱异喹啉生物碱AGP-replacement抗生素替代抗生素替代:Intestinal health肠道健康Performance 生产性能Feed efficiency料肉比A

11、cidifiers酸化剂Phytogenic additives植物源添加剂Natural essential oils植物精油Nature-identical products天然相似品Herbal extracts植物提取物Ground herbs草药粉Probiotics, yeast益生素，酵母Prebiotics益生元Yeast derivates酵母衍生产品Enzymes酶制剂4/2/202213Natural extract on powdered carrier 植物提取物植物提取物Extract of Macleaya cordata 博落回提取物Dosage: 20-60

12、g/t feed 剂量：每吨饲料添加20-60克Main effects 主要作用主要作用Mild antimicrobial & strong anti-inflammatory effect轻微的抑菌与很强的抗炎效果Used as major component in oral healthcare products用作口腔保健产品中的主要成份Isoquinoline Alkaloids 异喹啉生物碱4/2/20221414Benzophenanthridine alkaloids 苯并啡啶类生物碱苯并啡啶类生物碱Protopine alkaloids 原阿片碱原阿片碱Isoqui

13、noline Alkaloids 异喹啉生物碱15Post-AGP strategiesIsoquinoline alkaloidsMode of action 作用机理作用机理Efficacy in pigsConclusion16NF-BDNARibosome 核糖体Cytokines细胞因子Receptors 受体Mode of Action: Inhibition of NF-B 作用机理：抑制NF-kB Inhibition of NF-B activation抑制NF-kB激活Chaturvedi et al., 1997Isoquinoline alkaloids异喹啉生物碱异喹

14、啉生物碱17Anti-Inflammatory Effect of Isq. Alkaloids异喹啉生物碱抗炎效果Niewold, 2013Down-regulation of inflammatory markers in IPEC-J2-cells infected with E. coli 负性调节受大肠杆菌感染猪空肠上皮细胞的炎症标志物负性调节受大肠杆菌感染猪空肠上皮细胞的炎症标志物a,b,c (p0.001)*ASA = Acetyl salicylic acid 乙酰水杨酸(0.001%) FCR 饲料转化率饲料转化率 (n=12)Inflammation marker in j

15、ejunum: 空肠炎症标志物空肠炎症标志物iNOS (n=12) 诱导型一氧化氮合酶诱导型一氧化氮合酶 （n=12)(=inducible nitric oxide synthase) Linear effect of Sangrovit vs. Control (p0.01)Effect of OTC vs. Control (p0.01)*Oxytetracycline in feed 饲料中土霉素 200 mg/kgIsq. Alkaloids (mg/l)Isq. Alkaloids (mg/l)Anti-Inflammatory Effect of Isq. Alkaloids异喹

16、啉生物碱抗炎效果Khadem, Niewold et al., 2014University of Leuven, BelgiumLinear effect of Sangrovit vs. Control (p0.01)Effect of OTC vs. Control (p0.01)19Acute phase protein of weaning piglets (age: 28-70 days) (n=72) 断奶仔猪急性期蛋白断奶仔猪急性期蛋白 （28-70日龄）日龄）a,b (p0.05)Kantas et al., 2014Anti-Inflammatory Effect of I

17、sq. Alkaloids异喹啉生物碱抗炎效果20Post-AGP strategiesIsoquinoline alkaloidsMode of actionEfficacy in pigs 猪用效果猪用效果Conclusion4/2/202221采食量采食量 Feed intake +2.8%日增重日增重 Daily gain +6.3%料肉比料肉比 FCR -3.8%Performance (%) vs. Control Piglets生产性能（%）对比对照组仔猪Reduced Stress Prior to Slaughter屠宰前减少应急Artuso-Ponte, 2014Ohio

18、State University, USAControl 对照Isq. alkaloids in feed 饲料中异喹啉生物碱Isq. alkaloids in feed & water饲料与水中异喹啉生物碱Salivary cortisol as indicator of stress (n = 27)作为应急指标的唾液皮质醇水平（n=27)a,b p 0.05Day 1Day 14Day 27Day 2823a,b p 0.05Reduced Stress = Less Contamination减少应急 = 降低污染Artuso-Ponte, 2014Ohio State Uni

19、versity, USACarcass counts胴体残留量胴体残留量Prevalence in faeces粪便残留量粪便残留量Isq. alkaloidsIsq. alkaloids24Stress indicatorInflammation indicatorReduced Stress & Inflammatory Response减少应急及炎症反应a,b p 0.05Suwannathada, 2013Khon Kaen University, ThailandCTC + Isq. Alkaloids (50 g/t)CTC + Isq. Alkaloids (100 g/

20、t)25a,b p 0.05Enhanced Feed Intake & Litter Performance提高采食以及窝产仔性能CTC (150 g/t)CTC + Isq. Alkaloids (50 g/t)CTC + Isq. Alkaloids (100 g/t)Sow feed intake 母猪采食kg/d6.136.696.74Sow BW change 母猪体重变化kg-4.7-3.7-2.8Sow body condition at weaning (21 days)断奶时（21天）母猪体质3.1b3.5a3.4aPre-weaning mortality 哺乳猪

21、死亡率%9.1a6.9b6.5bPiglet weaning weight断奶仔猪体重kg6.03b6.48a6.49aSuwannathada, 2013Khon Kaen University, Thailand26Post-AGP strategiesIsoquinoline alkaloidsMode of actionEfficacy in pigsConclusion 结论结论27Conclusion 结论 Consumer demands to reduce antibiotics消费者渴望减少抗生素使用 Isoquinoline alkaloids in feed or water异喹啉生物碱用于饲料中或水中 Stabilization of health, feed intake & performance健康，采食量以及生产性能的稳定 Stress reduction 减少应急 Standardization & QC = key to