乳仔猪和种猪场肠道微生态平衡和免疫调控研究进展

ResearchadvancesinrelationtoimmuneIfunctionandmicrobialbalanceinthegastrointestinaltractofyoungpigs仔猪消化道免疫功能和菌群平衡研究进展ProfessorJohnPluskeMurdochUNIVERSITYInvitedpresentationatthe2012SummitontheVerticalIntegrationandValue-ChainBuildupofLivestockandAquacultureProductionToday'spresentation主要内容,OverviewoftheAustralianswineindustry澳大利亚养猪业概况•Thegastrointestinaltract-whatisguthealth?消化道-什么是肠道健康,Guthealth-thesucklingpig消化道健康哺乳仔猪,Guthealth-theweanlingpig消化道健康-断奶仔猪・Take-homemessages结论TheAustralianpigindustry:abriefoverviewThenumberofregisteredproducersinAustraliahasdecreasedovertime澳大利亚注册生产企业（者）的数量减少AustralianPigAnnual,2009-2010s&.atMMg3c-,aDa1鸵R:档・27§2D,aOCw.aKi『恤酥Theaveragenumberofsowsperherdhasincreasedovertime每群母猪的平均数量增加W带繆术芥方3职苹对爹妒歩逮妒妒带爹莆成材Year胃

From2ODSsowreumbenonrymila&^eHerdsizerangesfrom5sowsto40,000sowsAustralianPigAnnual,2009-2010母猪每群数量由5头上升到40,000头ThetotalnumberofsowsinAustraliahasdecreasedsince2008从2008年至今澳大利亚母猪总量在减少AustralianPigAnnual,2009-2010TMOaSows5001c=====#FromZDOSedwnumbersonlyavailable2009BrEedin。Sows:Z4礼!X）。Thenumberofslaughteringshasreducedbetween2006and20112006-2011年屠宰量减少MonthlyAustralianPtgSlaughteringsAustralianPigAnnual,2009-2010Breedingherdperformance,2008-2009繁殖猪群的生产性能ParameterUnitsAverageofallsystemsPigsweaned/sow/yearNumberofpigs21.1Numberbornalive,giltsNumberperlitter10.2Numberbornalive,giltsandsowsNumberperlitter10.7Stillbirths,%perlitter%ofpigletsborn7.7Sowmortalityrate,%%oftheherd12.0Sowturnoverrate%oftheherd655Farrowingrate,gilts%ofgiltsbred83.7Farrowingrate,giltsandsows%ofgiltsandsowsbred81.3Pre-weaningmortality,%%ofpigletsbornalive13.9PigsweanedperlitterNumberperlitter9.2WeaningageDays22.7LitterspersowperyearNumberoflitters2.3Summary:Australianpigindustry小结-澳大利亚养猪业Verysmalllevelofproductionbyworldstandards(=0.4%ofworldproduction),70-80%ofprocessedporkconsumedisimported^e.g.^Denmark,USAfCanada依据全球标准养猪业仍处于较低生产水平，7480%猪肉消费依靠进口(比如从丹麦、美国和加拿大)oRapidconsolidationofAustraliansownumbersintorelativelyfewbreedingherdsoflargersiae,母猪数量集中于相对较少的大规模繁殖猪群。•Fewerfarrow-to-finishfamilyownedunits家族式自繁自养模的单位减少<>,Moremulti-sitecontractoperations更多的多站点合同操作°,Increaseinthenumberandsizeofverticalintegrationenterprises一体化垂直管理企业数量和规模增加。Majorpartofpigproductionnationallyfoundinareasofhigherpopulationofeastandsouth-eastofAustralia,全国主要的养猪生产基地建在人口较多的澳大利亚东部和东南部地区•RegionsofhighestpopulationdensityA口密度最大的区域Australianindustryischaracterizedbyrelativelyhighhealthstatus,澳大利亚养猪业的特点是健康状况相对较高,NoPRRS,noFMDfnoTGEDiversityofhusbandry/housingsystems饲养体系多样性IntensivehousingsystemsStraw-basedsystemsDifferentoutdooraccommodationCurrentandfuturechallengesforthe澳大利亚养猪业目前和将来面临的问题•Environment环境•Welfare动物福利•Consumers消费者•Profitability盈利能力PorkCRCCRCFORHEGHINTEGRTTYAUSTRALIANPORKProgram1-Confinement-freeSowandPigletManagement♦Reducingthetimesowsspendinasowstallafterweaningandinpregnancy(grouphousiu容)减少断奶间隔♦Extensionoftheweaningagetoaccommodateoestrusinlactation延长断奶日龄以适应哺乳期发情•Program2-HerdHealthManagement猪群健康管理.Reducingtheuseofantibiotics(prophylactic,therapeutic)inpigproduction减少抗生素的使用•Program3-HealthyPorkConsumption健康的猪肉消费♦Increasingthefunctionality,con^stencyandreliabilityofAustralianproducedporkft>rconsumer增加功能性、质量稳定可靠猪肉产品的供给•Program4-Carbon-ConsciousNutrientInputsandOutputs注重环保营养品的投入和产出♦ReducingthecarbonfbotprintofpigfMoductioninAustralia降低养猪业的碳排放量“DeliveryoftheseoutcomeswilldifferentiateAustralianporkasahighintegritymeatthatiswelfare-optimal,premiumquality,safe,nutritiousandinhighdanand,whichcanbeproducedwhileconservingenergyandwaterresources,minimisinggreenhousegasemissionandmaintainingefficiencyandcostofproductionatalevelthatpromotesinvestment,growthandsustainabilityoftheindustry”这将把漠洲猪肉与其他国家的产品做出区隔，具备动物福利，优质，安全，营养要求高的高诚信肉类，同时节约能源和水资源，尽量减少温室气体排放并确保生产效率和成本，促进投资的増长和行业的可持续发展.GastrointestinaltractandguthealthWhatisguthealth?肠道健康•Difficulttodefine难以定义.Generalisedconditionofhomeostasis/homeorhesisofthegastrointestinaltract,inallphasesofgrowth动物生长全期消化道内环境稳定状态.€Guthealth，-viewedasanoutcome(positive,negative,thestatusquo)ofinteractionsbetween,肠道健康可®1为以下多种相互作用的结果.Nutrition(feedcomposition,presenceorabsenceofantibioticfeedadditives,particlesize,etc.),营养方面，包括日粮组成、抗生素添加与否、颗粒大小等.Immune6

activity7

(innate^acquired),免疫激活(天然免疫，荻得免疫).Microbiota(density,location,diversity,etc.)微生态区系(密度、分布、多样性等)(Williamsetal.,1997)Levelofimmunesystemactivationaffectsperformance6-27kgLW免疫系统激活水平对生产性能的影响ItemImmunesystemactivationDietarylysine,%ofthediet0.600.901.201.50Dailygain,___gramsU^High400556644663—357

49551。5°4DailyfeedLowintake,"grams

High896102510521002889954889911Low445544613662Gainfeed,g---perkgC^Hiqh395522581

565>Whatcontributestoahighlyfunctionalgut?影响肠道发挥强大功能的因素FEEDcomponentsSchematicpresentationofthegastrointestinaldefencebarriersystemandeffectorsites(afterWang,1995)消化道生物屏障系统和效应位点示意图LuminalfactorsEpithelialfactorsSubmucosalfactorsEpithelialbarrierfunctionPhospholipidlayerMucuslayerTightjunctionAA-cellEnterocyTeMacrophageLymphocyteLeukocyteLymphtubeStabilityUnstableStable(Sporetal.,2011；

Nat.Rev.Microbiol.9：279-290)Lifetimestabilityofthegastrointestinaltractmicrobiota消化道微生物区系稳定性EarlylifeAdult----->AgingGutmicrobialdysbiosisassociatedwithdisease一humanexamples与疾病相关的菌群失衡-以人为例HuhtyccfrtrqlfWMitPositive/negativeeffectsofbacteria细菌的正负效果OUStomachSmallIntestineCecumLargeIntestine<---PROXIMALGTIT—><—DISTALGUT―>PrimarilyGrampositivefacultativeanaerobic:bacteriaNEGATIVEEFFECTSCompetewithhostforenergyandproteinProductionofgrowthdepressingmetabolitesPOSITIVEEFFECTSCompetitiveexclusionofpathogensPrimarilyanaerobicbacteriaPOSITIVEEFFECTSProduceenergyfromundigestedfeedCompetitiveexclusionofpathogensNEGATIVEEFFECTSProductionofgrowth。depressingmetabolites(Gaskinsetal.,2002)Microbiotacompositionisessentialforimmunehomeostasisandbalance徜生物区系组成对免疫系统的稳定和平衡非常重要PsthobiontsProbioPathogenmmatsonRegulationImmunologicaldysequilibriumInflamnnationRegulation(ReproducedwithkindpermissionfromProfessorD.Kelly)'*imunologkalequilibrium、.CommensalsColonizationbygutbacteriadrivedevelopmentofimmunesystem肠道细菌的定植促进免疫系统发育•Littledevelopmentofmucosalimmunesystemingerm-freeneonatalpiglets无菌初生仔猪粘膜免疫系统儿乎没有发育•Nodevelopmentofintraepitheliallymphocytes肠上皮内淋巴细胞没有发育•LaminapropriaTcellsdonotappearinsignificantnumbers固有层T细胞数量不显著•NoincreaseinCD4+andCD8+lymphocytesinthelaminapropria固有层CD4、CD8、淋巴细胞数量没有增加•Peyer'spatchesremainsmall普氏体很小ImprintingofthegutimmunesystembythecommensalbacteriaMicrobiota共生菌群影响肠道免疫系统Germ-free*Experiinentswithgerm-fieerevealmanydifferentsystemsareshapedbytheIgAA

..microbiotasmallintestine•StiniulalionofinmiunesystemrequiiesIgAPeyerpschighdosesofbacteriapatchE••LivebacteriaarebetterstimulusforCD44J<為詞四fitZuiiimiimesystemthandeadintestine験.1■尊*曲尊-*-■：HypoplasticMiicewithnormsiIgutmicrobiota(ReproducedwithkindpermissionfromProfessorD.Kelly)与肠上皮细胞和树状细胞的相互作用Q1O1QATreguJatorycells(Tregs)ceHscriticalinimmunehomeostasis.Importanttherapeutsctargetsinautoimmunity(ReproducedwithkindpermissionfromProfessorD.Kelly)QlQlQlQlQlQlQlQlQlQlQlQ□Csubksel1ADendriticcells(DCs)keyinitiatorsandregulatorsfT}oftheadaptive-cy顷3immuneresponseTh1Th2TMTAEpithelialcells(ECs)FirstlineofcontactwithbacteriaBacteriainteractwithepithelialcellsanddendriticcellsintheintestineDevelopmentofthemucosalimmunesystemintheyoungpig仔猪粘膜免疫系统的发育Supplementary“protection”Stageofimmunologicalmaturity(fromStokes,2006)Birth4weeks6-8weeksSummary小结•Gutbacteriadrivedevelopmentoftheimmunesystemimmediatelyfrombirth肠道细菌从动物出生就促进免疫系统的发育。•Developmentneedstobecontrolled,butprecisemechanismsforachievingthisareunknown这种作用是受控制的，但其精确机制尚不明确。•Homeostasisislessenergy-costlythanactiveinflammatoryresponsesthatoccurintheabsenceofregulationandcontrol与机休调控缺失时出现的主动炎症反应相比，微生态平衡需要的能量消耗更少。Guthealth.thesucklingpigColostrum-thevitalsecretion初乳-至关重要的分泌物Newbornpigisimmunologicallynaive新生仔猪获得天然免疫SwineareaGroupIIImammal,soepitheliochorialplacentationpreventsimmunoglobulintransfer所utero猪是III组哺乳动物，在子宫内上皮绒毛形成胎盘可阻止免疫球蛋白转移Maternalsupplyerfpassiveimmunitymustoccurafterbirth,出生后母体会提供被动免疫•Non-specifictransfer(pinocytosis)insmallintestineintobloodwppl?小肠中经非特异性传递进入血液供应•隽刘果臬transferIgGacrossmucosadisappearsinfirst24-36hoflifeffi,最初的24-36小时，传递IgGilii粘膜的能•HigherconcentrationsofIgA(inparticular)providemucosalprotection高浓度的IgA提供粘膜保护Passiveimmunityalsoprovidesdefensefactorsviamolecules,被动免疫还可通过分子提供防御因子•LadtoferHn.cytokines&chemGkir必annateimmunity)Nsozvme汛铁蕾白、细胞因子和趋化因子(天然免疫)、溶菌酶Pigimmunoglobulins(Igs)猪免疫球蛋白•Afamilyofproteinsthatareimportantforgrowth,developmentofimmunity,andsurvival对动物生长、免疫发育、生存起重要作用的一系列蛋白质,Threemajorlgclasses：三类主要免疫球蛋白•IgG：•Quantitativelymostimportantinpigserumandcolostrum,hastwosubclasses(lgG1andIgG/anaprovidesforsystemicimmunity'在猪血清和初乳中含量较高，具有两个亚型，供给系统免疫•IgM：•Theseantibodiesplaymajorroleindefenceagainstviruses这些抗体在防御病毒方面起重要作用•IgA：•Provideslocalimmunityatmucosalsurfacesfegflungs,gastrointestinaltract在希膜表面展峪局部虽疫[Bourne(1973),Proc.Nutr.Soc.32：205]IgMIgAIgGIgMIgATransferofIgsfromserumtocolostrumandmilkinthesow母猪免疫球蛋白由血清向初乳及乳中转移Serum:ColostrumtransferSerum:Milktransfer[Bourne(1973),Proc.Nutr.Soc.32：205]wII-Colostrum15600lgderivedfromscrum(%)Milklgformedinmammarygland(%)Pigletsneedtoconsumecolostrumasquicklyaspossible仔猪需尽早采食初乳•LeDividichetaL(2005),•Colostrumintakeexplains0.86-0.88ofvariationinpigletweightgainbetweenbirthand24hafterbirth出生24小时内，仔猪体重0.86-0.88的变异由初乳摄取量导致•Pigletsneed160-170gcolostrumperkgbodyweightforsurvival仔猪要摄取16。-170g/kg体重初乳以满足生存需要♦SynthesisofIgGbypigletpositivelyrelatedtoamountofmaternalIgGabsorbed(Rookeeta^2003)仔猪IgG的合成与母体IgG吸收量呈正相关•Pigletsthatsucklaterafterbirthhavelowerserumy-globulinconcentrations出生后没及时哺乳的仔猪血清y球蛋白浓度较低•Pigletssurvivingto2idofagehavehigherserumy-globulinconcentration21日龄的仔猪血清y球蛋白浓度较高Changesincompositionoflipidflactoseandproteinincolostrumfrombirthoffirstpigletto36h仔猪出生36小时内，初乳中脂肪、乳糖和蛋白质组成的变化[LeDividichetal.(2005),J.Agric.Sci.143：469]MoreIgGat7daysofagemeansmoreIgGat28daysofage7日龄时IgG水平高意味着28日龄时其水平也较高PlasmaIgGat7days(mg/ml)[Rookeetal.(2002),Livest.Prod.Sci.78：13](Emm)sx-a崙IEeesee:RoleofenvironmentinmicrobiotaandimmunityinthegutRoleofenvironmentinmicrobiotaandimmunityinthegut环境在肠道微生物区系和免疫中的作用,Earlymicrobialcolonizationofthegutreducestheincidenceofinfectiousinflammatoryandautoimmunediseases(Frank2007)肠道微生物尽早定植可以降低感染性炎性和自身免疫病的发生♦Studiesshowthatchildhoodhygieneisasignificantriskfactorfordevelopmentofinflammatoryboweldisease(Pendersetat,2OO6)f研究表明幼儿早期卫生保健有导致炎性肠病的风险一^Hygienehypothesis^,andthepotentialimportanceofmicrobialcolonizationduringearlylife卫虫傷设理论，动物生长車期微生物定植的潜在重要性♦Theextenttowhichearly-lifeenvironmentimpactsonmicrobialdiversityandsubsequentimmuneprocesseshasnotbeencomprehensivelyinvestigatedinpigs生长早期环境对微生物多样性和免疫过程的影响程度在猪上尚未深入研究OutdoorSowrearedIndoorSowrearedIndoorIsolator+AntibioticsOtherPepftos^reptococcacemGkysirtd/ac&aeWe^ffQneffaceaeLachnospjraceaeRiJiTwhococcaoeaeLeuiwiosfoom皿aeStrepto&acwacMeLactobacitiaoes^BacillaleBErysipelolrictiiGjammaproeeobaclsriaBelaprovedbackedaEpsiksnproteobacteriaAlphapraceobacteria□Bacteroidetes□□□Prewo^eJtaceaeBact&roidaceaeFcfpftjTOnrorw曲Actinot>3deria(Mulderetal.,BMCBiology2009,7:79)mucosa-associateddiversity生长早期环境改变与粘膜相关微生物多样性«TJ100%75%50%25%0%Phylogeneticdistributionofbacteriafromilealandfecalsamplesindifferenthousingenvironments不同养殖环境下回肠及排泄物中细菌系统发育分布(Mulderetal.,BMCBiology2009,7:79)FirmicutegOtherActinobaciBribPro®DbecleriaBaDtercidetes□IN■OUT□IR□INS□OUTSLactobacilliinilealandfecalsamplesfrompigletsandsowsindifferentenvironments不同环境下仔猪、母猪回肠及排泄物中乳酸杆菌情况•EDifferentiallyexpressedgenesintheileumofanimalshousedindifferentenvironments不同养殖环境下回肠表达基因差异SpecificallyassociatedIRvsOUTINvsOUT□Upregulaleclgems□Dawnragulaledgeneswithinflammatorygenes,e.g.Type-1IfN(Mulderetal.,BMCBiology2009,7:79)Guthealth-the\AAaanlinnnin<<J.......-一Theweaningprocess断奶过程•Weaningimposesmultipleandsimultaneousstressorsonyoungpigs.断奶会同时对仔猪带来多种应激•Nutritional,营养因素•Dietshighinindigestiblecarbohydrates,lowerinlipid,changedaminoacidprofile日粮中不可消化碳水化合物含量高，脂肪含量低，氨基酸组成变化•Changesindietformandpresentation日粮形态、组成变化•Psychological,心理因素•Mixingandmovingpigs,separationfromthesow合并群，与母猪分开•Environmental,环境因素•Temperature/feederandwaterlocations^™.度，料槽、饮水器位置•''Growthcheck。生长检查•Aimafterweaningistoreducethenegativeimpactweaninghasonproduction,diseaseincidencefmorbidityandmortalityB的是降低断奶对生产性能、发病率和死亡率带来的负面影响Feedintakeafterweaningandgutbarrierfunction断奶后饲料釆食和肠道屏障的功能•Periodoftemporarystarvationafterweaningcompromisesgutbarrierfunction,断奶后暂时性饥饿过程破坏肠道屏障作用♦Lowfeedintake^低釆食量•Increasesnumbersoflymphocytesandinfiltratedcellsinepithelium上皮中淋巴细胞和浸润细胞数量增加,Causesatransientinflammatoryresponse导致瞬间炎症反应,Decreasesepithelialtissueresistance(more"leaky"intestines)降低上皮组织抵抗力--—^6/丿/•VillusheightrfOCryptdepth峪

△CellproliferationL_♦■■.Acutephase(Adaptivephase~►I*TrFT'''!rrlJj151015Dayspost-weaningDayspost-weaning(fromBurrinandStoll,2003;InWeaningthePig:ConceptsandConsequences)Therearetwophasesofchangeinthesmallintestineafterweaning断奶后在小肠中发生两个阶段变化150湛aeoeCD，5000150OO,1sucMM.Edolug」①CLDietandsmallintestinalstructure5daysafterweaningPigsfedcows'wholemilkadlibitumPigsfedconventionalstarterdietadlibitum(Pluske,1993)Foodintakeandaveragevillousheightinmilk-fedpigs哺乳仔猪釆食量和平均绒毛高度1(pim)700-1600-500-400-300-200_____________________________0200400600Drymatterintake(gday-1)r=0.82P<0.001(Pluskeetal.,1997,Livest.Prod.Sci51:215-236)Villousheightdeterminesemptybodyweightgainafterweaning断奶后肠绒毛高度决定净增重=6oo1o400-o200r2=49%0-200T__________________Averagevillousheight(pm)Averagevillousheight(pm)FedstarterdietafterweaningEmptybodygain(g/day)Emptybodygain(g/day)<60Fedmilkafterweaning(Pluskeetal.,1996)300400500600700200300400500ADFIday0-34,g/d0050100150200250300350400ADFIday0-8,g/d0050100150200250300350400ADFIday0-8,g/dFoodintakeduringwk1afterweaningdeterminesapproximately40%offoodintakeandgainbetween8-23KG(Bruininxetal.,2004)100y=1.097x+343.72Theimportanceofearlyfoodintake：thepracticalperspective早期釆食的重要性-实践应用pa4CO6>ep00<Inflammatoryandimmunologicalconsequencesoflowfeedintakeafterweaning断奶后低釆食量导致炎症和免疫学上的后果•IncreasedT-cellnumbers(cellsof'innate'immunesystem)inintestinesofpigsassociatedwithnutrientdeprivation由于营养不良引起猪肠道T细胞数量增加•T-cellexpansioniscorrelatedto,T细胞的增加与以下方面有关•Poorerepithelialintegrity较差的上皮细胞完整性•Localinflammation(up-regulationofcytokinegeneexpressioninsmallintestine,e.gIL-邛，IL-6,TNF-a)局部炎症•Compromisednon-immunologicaldefencemechanisms(mucinetc.)缺乏抵抗力的非免疫性防御机制0T-lymphocytenumbersincreaseinvilliofstarvedpiglets饥饿状态下仔猪肠绒毛中T淋巴细胞数量增加No.ofcells141210(Ganessunkeretal.,1999)8BaselinePigsfedfor7dafterbirth6bOralfedFedbyintravenouscatheter□Jejunum□Ileumaa42aaFunctionsofpro-inflammatorycytokines促炎细胞因子的功能■IHematopoiesisT-cellproliferation(Grimble,1998)IgswitchingChemotaxisSummary:theimportanceofarapidtransitiontofeedintakeafterweaning小结-断奶后釆食快速过渡的重要性•Preventionofdamagetotheintestinalstructure(e.g.rPiuskeetal,2996；vanBeers,1996)

防止损害肠道结构,Increasedmaintenancerequirementsinweekaafterweaning(eg.,Schramaetal.,2997)

增加断奶后一周的维持需要•PreventionofaHleakygut"(eg*SpreeuwebergetaL,2001；Verdonketal.f2001)防止肠漏症的发生•PreventionofadecreaseindigestivecapacityMakkink,1993)防止消化力降低,Reductionofpost-weaningdiarrhoea?(MadecetaL,1998；CarstensenetaL,2005)减少断奶后腹泻SolutionstoimprovingguthealthafterweaningI—*w_________上八xxu■攻晋觀矶后购追谜康旳惜她IllTheJournEilofNutritionNutritionandOisMseSpecificfeedingredientsandmucosalfunction:spray-driedplasmaproducts特定饲料原料和粘膜功能-喷雾干燥血浆产品DietaryPlasmaProteinSupplementsPreventtheReleaseofMucosafProinflammatoryMediatorsinIntestinalInflammationinRats1,2Anna凹.-丘照叫&1.|灯心Mia'fi/JovkrPnEo/Louhkusscll,"JoyCampbctL/EricWtaver.*Jfj*CrtnishawLandMiquelMureto14E>rpan:r7?c.nrofMiysiflioEjy,Fjh：uIevPharrrui；rmtdNuEHlhia^iidf<K>d、盘日/Rfwarrh[nwi=u-tv厲止*UnnenilyofBjir».<iru,BarcdonaSpaio；J-umprS.A.t

C,r^iinllrri0H4flSp：itn：^APCInc,1A5002k：BrtdhFro(ianrl-kdlihandBiD£(igLcaEi,Anktny,JATIXIJ]Effectsoffeedingplasmaandimmunoglobulinsonmucosalimmunity饲喂血浆和免疫球蛋白对粘膜免疫系统的影响Ratsfeddietssupplementedwith(i)spray-driedporcineplasma(SDP；

8%ofdiet),(ii)Igconcentrate(IQ1.5%ofdiet),or(iii)Controldiet(milkproteins)•Diets(i)and(ii)bathhadsimilarIgGcontents(10g/kgofdiet)•Intestinalinflammationinducedbyi.p.administrationofS.aureusenterotoxinB(SEB)ondays32and35afterbirthAuthorsmeasuredexpressionof;-Pro-inflammatorycytokines(IFNy,TNFa#IL-6)andinflammatorymediators(LTB。andinducibleoxidenitricsynthase(iNOS))-Anti-inflammatorycytokines0L-io,TGFp)Theyalsoexpressedaratioofpro-inflammatory:anti-inflammatorycytokinesRatskilled6hoursafterseconddoseofenterotoxinRatioofpro-:anti-inflammatorycytokinesisalteredusingplasmaorIgconcentrate饲喂血浆和免疫球蛋白可改变“促炎症因子/抗炎症性细胞因子”比例•EnterotoxinBincreasedtheratioofpro-:anti-inflammatorycytokinesinA:jejunum,B:Peyer'spatches,andC:serum肠毒素B提高空肠、派尹尔氏淋巴结、血清中促炎症因子/抗炎细胞因子的比例。•Feedingeitherspray-driedplasmaorIgconcentratepreventedtheincreaseinthisratio饲喂喷雾干燥血浆或免疫球蛋白可防止这一比率升高。(Perez-Bosqueetal.,

2010；

JournalofNutrition140:25-30)B43■bbliIL-6AL-HD■nNFa/IL-10ncctntrol■呂E目OSEB-SDP«SEB4CoCorrtr&rflSErgiDaysofdietarytreatmentSpray-driedporcineplasmareducesinflammationinthesmallintestineofpigsafterweaning喷雾干燥血浆减少断奶仔猪小肠内的炎症反应Spray-driedporcineplasmareducesinflammationandimmunesystemactivationafterweaning喷雾干燥血浆降低断奶仔猪炎症反应和免疫系统的激活(Jiangetal.,

2000；

J.Nutr.130:21-26)D^ysofdietarytreatmentM=iwEscherichiacoOandpost-weaningcolibacillosis(diarrhoea)大肠杆菌和断奶后大肠杆菌病(腹泻)Most£.co/rassociatedwithpost-weaningcolibadI(0515areenterotoxin-producing,P-haemolyticstrains,eg,O13%O141与断奶后腹泻相关的大肠杆菌是产生内毒素的片溶血性菌株Diseaseofsmallintestine,populationsinlargeintestine小肠疾病，大肠菌群Insmallintestine,virulentE.coliattachtoreceptors(egfF4)andcausehypersecretorydiarrhoeaviaenterotoxins^e.g.fSTaf5Tb小肠中，有毒的大肠杆菌与受体结合,通过内毒素导致腹泻Cancausedeath,morbidity引起动物发病，甚至死亡Associationsbetweendietproteinlevelanddigestivedisturbances0粮蛋白水平与消化紊乱间的关系•Proteinlevelsinstarteddietsvary,uptomaximumof250g/kg开口料中蛋白水平最高到250g/kg。•

Proteinthatisnotdigestedinthestomachorsmallintestinegoesintothelargeintestine蛋白质在胃和小肠中不被消化，而是进入大肠。•Thebacteriaproduceby-products,suchasammonia,thatmaycausescoursafterweaning细菌产生的代谢产物（如氨）导致动物断奶后腹泻。•Higherlevelsofcrudeproteinwereassociatedwithmorediarrhoea粗蛋白水平越高越容易引起腹泻。Feedinglowproteindietstoreducescoursafterweaninq断奶后饲喂低蛋白日粮可减少腹泻,Intheory：feedinglowproteindiets(<180gofproteinperkgofweanerdiet)shouldreducescours断奶后饲喂低蛋白(每kg日粮中蛋白质少于180g)日粮可以减少腹泻。*However-difficulttomakea'balanced'dietatthisamountofprotein,unlessyouaddexpensivesyntheticaminoacids,但是此蛋白水平下很难实现平衡日粮，除非添加昂贵的合成萼基酸。-Commercialmanufactureofvalineandisoleucine^氨酸、异亮氨酸的工业化生产•Previousstudies-lowproteindietsreducescoursbutalsoreducegrowthafterweaning,whentheyarenotfaormultedproperly过去研究表明，当配比不适当时，低蛋白日粮可减少腹泻也会降低断奶后生长效率。Aimsofthestudies研究目的•Canareductionindietaryproteinpreventscoursafterweaning?断奶后降低日粮蛋白水平能否预防腹泻？•Howlongdoweneedtofeedalowproteindietfor?低蛋白日粮要饲喂多久？•Willalowproteindietreducegrowthafterweaning?低蛋白日粮在断奶后会降低生长效率吗？Experimentaldesign试验设计TreatmentsHP14(n=24)LP14(n=24)LP7(n=24)Phase-IIProteinlevel256g/kg175g/kg175g/kg212g/kgFeedingduration14d14d7dUpto28d•AlldietscontainedLys,Met,ThrandTryp•LPdietssupplementedwithisoleucineandvaline•NOantimicrobialcompoundsuseinthediets■Animals•Pigsweanedat21-23d(about6kg)21-23天的断奶仔猪(大约6公斤)•HalfofthepigspertreatmentwereinfectedwithE.colifandotherhalftreatedwithbroth一组感染大肠杆菌，另一组做对照O149;K91;K88Total19mlover3d(109CFU/ml)三天共19ml(109

CFU/ml)EnterotoxigenicEcollinfectionreducesproteinutilization感染可产生肠毒素的大肠杆菌降低蛋白利用率HP,NonLP?NonHP,infectedLP,infectedinfectedinfectedI■TotaldietaryNintake,gApparentilealdigestibility,%IlealNflow,gperd1.DIETeffectonNintake(P<0.001)2.INFECTIONeffectonAID(P<0.05)3.DIETandINFECTIONeffectsonilealNflow(P<0.05)(Heoetal.,2010;Anim.FeedSci.Tech.,160:148-159)FecalammoniaN,mg/kgLowproteindietsreduceproductionofammoniaingut低蛋白日粮减少肠道中氨的产生口HP14口LP7口LP14600-Treatments(Heoetal.,2009)Areductionincrudeproteinsupplyinthececumreducesmeasuresofproteinfermentation盲肠中粗蛋白水平的降低可减少蛋白质发酵水平Crudeproteincontent,gperkgdietItem255199P-valueNH3-N,mg/L150101<0.001Amines,mMPutrescine0.881■U.540.002Cadaverine0.580.580.969VFA,mMIsobutyricacid21Isovalericacid0.300.140.005TotalVFA85620.036(afterHtooetal.,2007)Lowproteindietsincreasethedrymattercontentofthefaeces低蛋白日粮可增加粪便中干物质成分口HP14口LP7口LP14d7Non-infectedd7Infectedd14Non-infectedd14InfectedTreatments(Heoetal.,2009；

J.Anim.Sci.,87：2833-2843)40000321Mcosamwuobi6o-140-120-100-8o-60-40-20-Lowproteindietsreducepost-weaningdiarrhea低蛋白日粮降低断奶后腹泻口HP14口LP7口LP14d4-7Noninfectedd4-7Infectedd8-9Noninfectedd8-9InfectedTreatmentsd10-12Noninfectedd10-12Infected(Heoetal.,2009；

J.Anim.Sci.,87：2833-2843)XCDPU-£oll」」eQReducingcrudeprotein(CP)inthedietreducesloosefaecesandreducesurine降低日粮中粗蛋白可减少稀便和尿液(afterLeBellegoandNoblet,2002)9Item22.420.418.416.9%changeBW,kgStart11.712.011.812.0Final26.026.827.226.8Consistencyoffeces(%oftotalnumberofdaysintheexperiment)Soft14.7Liquid2.0Urineproduction,gperday757643625481-35%Feedingbalancedlowproteindietsdoesnotdecreaseproduction饲喂平衡低蛋白日粮不会降低生产性能□ADGOADFIAG:F.r.------------------------------(Infection：P<0.001)Treatments(Heoetal.,2009；

J.Anim.Sci.,87：2833-2843)HP14LP7LP14HP14LP7LP14Non-infectedInfectedFeedingalow-proteindietforonly5daysreducesdiarrhea饲喂5天低蛋白日粮可减少腹泻2008；

Arch.Anim.Nutr.,62：343-358)(Heoetal.,■R-HPLP5—M—LP7—4--LP1450o4ECUCLIBESPigsfeddifferentcerealsvaryindiarrheaafterweaning断奶后饲喂不同谷物对腹泻的影响P<0.01CornBarleyRolledOatsRicePigschallengedwithoraldoseof2x109CFU/pig；6pigsweanedat21dofage/treatment；Diarrheascore0=normalfeces;4=severe(Buckinghametal.,2006)口服剂量为每只猪2x109CFU/pig；21日龄断奶；腹泻指数0代表正常粪便。Also:reducedremovalofpigsfromnurseryforbarleyvscorn:3.6vs7.1%(P<0.05)(Perez-Mendozaetal.,2006)•cadaverine•putrescine•tryptamine•histamine]Amines,mM(Bolduanetal.,1988)8r6.75765-645.752345678CFinfeed,%Serumurea,mM3——I---1——I——I---1——5.5Ahigherindigestiblefibrecontentreducesbacterialnitrogenmetabolism不可消化纤维含量较高可降低细菌氮代谢[Biogenicamines:Feedprocessinginfluencessurvivalofpathogenicbac