肠道菌群紊乱和自闭症

肠道菌群紊乱和自闭症PatholBiol(Paris).2015Feb;63(1):35-42.doi:10.1016/j.patbio.2014.10.003.Epub2014Nov2.The"psychomicrobiotic":Targetingmicrobiotainmajorpsychiatricdisorders:Asystematicreview.FondGi,BoukouaciW2,ChevalierG3,RegnaultA4,EberlG3,HamdaniN5,DickersonF6,MacgregorA?.BoyerLs.DargelA5.OliveiraJ2.TamouzaR2,LeboyerM5.AuthorinformationdnsermU955,FondaMentalFoundation,Paris-Estuniversity,ChenevierHospital,AP-HP,GHUMondor,DHUPe-Psy,PavillonHartmann,40,rueMesly,94000Creteil,France.Electronicaddress:guillaume.fond@.2Jean-DaussetLaboratory&Inserm,UMRS940,Saint-Louishospital,1,avenueClaude-Vellefaux,75010Paris,France.3Unitededeveloppementdutissulymphoide,InstitutPasteur,25,rueduDr.Roux,75724Paris,France.4lnserm,InstitutPasteur,aviesan/institutmulti-organismesimmunologie,hematologieetpneumologie(ITMOIHP),batimentBiopark,8,ruedelaCroixJarry1(er)etage,75013Paris,France.5InsermU955,FondaMentalFoundation,Paris-Estuniversity,ChenevierHospital,AP-HP,GHUMondor,DHUPe-Psy,PavillonHartmann,40,rueMesly,94000Creteil,France.6StanleyResearchProgram,SheppardPrattHealthSystem,6501N,CharlesStreet,MD21204Baltimore,UnitedStates.7InsermU1061,academicadultpsychiatrydepartment,Montpellier1university,LaColombierehospital,MontpellierCHRU,191,avenuedudoyenGaston-Giraud,34295Montpelliercedex,France.sEA3279-Self-perceivedHealthAssessmentResearchUnit,SchoolofMedicine,LaTimoneUniversity,27,boulevardJean-Moulin,13385Marseillecedex05,France.AbstractThegutmicrobiotaisincreasinglyconsideredasasymbioticpartnerinthemaintenanceofgoodhealth.Metagenomicapproachescouldhelptodiscoverhowthecomplexgutmicrobialecosystemparticipatesinthecontrolofthehost'sbraindevelopmentandfunction,andcouldberelevantforfuturetherapeuticdevelopments,suchasprobiotics,prebioticsandnutritionalapproachesforpsychiatricdisorders.Previousreviewsfocusedontheeffectsofmicrobiotaonthecentralnervoussystemininvitroandanimalstudies.Theaimofthepresentreviewistosynthetizethecurrentdataontheassociationbetweenmicrobiotadysbiosisandonsetand/ormaintenanceofmajorpsychiatricdisorders,andtoexplorepotentialtherapeuticopportunitiestargetingmicrobiotadysbiosisinpsychiatricpatients.BehavBrainRes.2015Feb1;278:542-8.doi:10.1016/j.bbr.2014.10.050.Epub2014Nov6.Intracerebroventricularinjectionofpropionicacid,anentericmetaboliteimplicatedinautism,inducessocialabnormalitiesthatdonotdifferbetweenseizure-prone(FAST)andseizureresistant(SLOW)rats.ShultzSR1,AzizNA2,YangL3,SunM2,MacFabeDF4,O'BrienTJ2.Authorinformation〔MelbourneBrainCentre,DepartmentofMedicine,TheRoyalMelbourneHospital,TheUniversityofMelbourne,Parkville,VIC,Australia.Electronicaddress:sshultz@.au.2MelbourneBrainCentre,DepartmentofMedicine,TheRoyalMelbourneHospital,TheUniversityofMelbourne,Parkville,VIC,Australia.3MelbourneBrainCentre,DepartmentofMedicine,TheRoyalMelbourneHospital,TheUniversityofMelbourne,Parkville,VIC,Australia;DepartmentofHistologyandEmbryology,KunmingMedicalUniversity,Kunming,Yunnan,China.4TheKileePatchell-EvansAutismResearchGroup,DepartmentofPsychologyandPsychiatry,UniversityofWesternOntario,London,ON,Canada.AbstractAutismisacomplexneurodevelopmentaldisorderthatischaracterizedbysocialabnormalities.Genetic,dietaryandgut-relatedfactorsareimplicatedinautism,howeverthecausalpropertiesofthesefactorsandhowtheymayinteractareunclear.Propionicacid(PPA)isaproductofgutmicrobiotaandafoodpreservative.PPAhasbeenlinkedtoautism,andPPAadministrationtoratsisananimalmodelofthecondition.Seizure-prone(FAST)andseizure-resistant(SLOW)ratswereinitiallydevelopedtoinvestigatedifferentialvulnerabilitytodevelopingepilepsy.However,FASTratsalsodisplayautistic-likefeatures,andhavebeenproposedasageneticmodelofautism.HereweexaminedtheeffectsofPPAonsocialbehaviorinFASTandSLOWrats.AsingleintracerebroventricularinjectionofPPA,orphosphate-bufferedsaline(PBS),wasadministeredtoyoung-adultmaleFASTandSLOWrats.Immediatelyaftertreatment,ratswereplacedinsame-treatmentandsame-strainpairs,andunderwentsocialbehaviortesting.PPAinducedsocialabnormalitiesinbothFASTandSLOWratstrains.WhiletherewasnoevidenceofsocialimpairmentinFASTratsthatwerenottreatedwithPPA,theseratswerehyperactiverelativetoSLOWrats.Post-mortemimmunofluorescenceanalysisofbraintissueindicatedthatPPAtreatmentresultedinincreasedastrogliosisinthecorpuscallosumandcortexcomparedtoPBStreatment.FASTratshadincreasedastrogliosisinthecortexcomparedtoSLOWrats.TogetherthesefindingssupporttheuseofPPAasaratmodelofautism,butindicatetherearenointeractiveeffectsbetweenthePPAandFASTmodels.PhysiolBehav.2015Jan;138:179-87.doi:10.1016/j.physbeh.2014.10.033.Epub2014Nov6.GastrointestinalmicrobiotainchildrenwithautisminSlovakia.TomovaAi,HusarovaV2,LakatosovaS2,BakosJ2,VlkovaB3,BabinskaK2,OstatnikovaD2.Authorinformation1lnstituteofPhysiology,ComeniusUniversity,Bratislava,Slovakia.Electronicaddress:aleksandra.tomova@fmed.uniba.sk.2lnstituteofPhysiology,ComeniusUniversity,Bratislava,Slovakia.3lnstituteofMolecularBiomedicine,ComeniusUniversity,Bratislava,Slovakia.AbstractDevelopmentofAutismSpectrumDisorders(ASD),includingautism,isbasedonacombinationofgeneticpredispositionandenvironmentalfactors.Recentdataproposetheetiopathogeneticroleofintestinalmicroflorainautism.Theaimofthisstudywastoelucidatechangesinfecalmicrobiotainchildrenwithautismanddetermineitsroleinthedevelopmentofoftenpresentgastrointestinal(Gl)disordersandpossiblyothermanifestationsofautisminSlovakia.Thefecalmicrofloraof10childrenwithautism,9siblingsand10healthychildrenwasinvestigatedbyreal-timePCR.ThefecalmicrobiotaofautisticchildrenshowedasignificantdecreaseoftheBacteroidetes/FirmicutesratioandelevationoftheamountofLactobacillusspp.OurresultsalsoshowedatrendintheincidenceofelevatedDesulfovibriospp.inchildrenwithautismreaffirmedbyaverystrongassociationoftheamountofDesulfovibriospp.withtheseverityofautismintheAutismDiagnosticInterview(ADI)restricted/repetitivebehaviorsubscalescore.TheparticipantsinourstudydemonstratedstrongpositivecorrelationofautismseveritywiththeseverityofGIdysfunction.ProbioticdietsupplementationnormalizedtheBacteroidetes/Firmicutesratio,Desulfovibriospp.andtheamountofBifidobacteriumspp.infecesofautisticchildren.Wedidnotfindanycorrelationbetweenplasmalevelsofoxytocin,testosterone,DHEA-Sandfecalmicrobiota,whichwouldsuggesttheircombinedinfluenceonautismdevelopment.Thispilotstudysuggeststheroleofgutmicrobiotainautismasapartofthe"gutbrain"axisanditisabasisforfurtherinvestigationofthecombinedeffectofmicrobial,genetic,andhormonalchangesfordevelopmentandclinicalmanifestationofautism.JNeurosci.2014Nov12;34(46):15490-6.doi:10.1523/JNEUROSCI.3299-14.2014.Gutmicrobesandthebrain:paradigmshiftinneuroscience.MayerEAi,KnightR2,MazmanianSK3,CryanJF4,TillischK5.Authorinformation〔OppenheimerCenterforNeurobiologyofStress,DepartmentsofMedicine,Physiology,andBiobehavioralSciences,DivisionofDigestiveDiseases,DavidGeffenSchoolofMedicineatUniversityofCalifornia,LosAngeles,LosAngeles,California90095,emayer@.2HowardHughesMedicalInstituteandDepartmentsofChemistry&BiochemistryandComputerScience,andBioFrontiersInstitute,UniversityofColoradoatBoulder,Boulder,Colorado80309.3DepartmentofBiologyandBiologicalEngineering,CaliforniaInstituteofTechnology,Pasadena,California91125.4DepartmentofAnatomy&NeuroscienceandAlimentaryPharmabioticCentre,UniversityCollegeCork,Cork,Ireland,and.5OppenheimerCenterforNeurobiologyofStress,DepartmentsofMedicine,Physiology,andBiobehavioralSciences,DivisionofDigestiveDiseases,DavidGeffenSchoolofMedicineatUniversityofCalifornia,LosAngeles,LosAngeles,California90095,DepartmentofMedicine,DivisionofIntegrativeMedicine,VeteransAdministrationGreaterLosAngelesHealthcareSystem,LosAngeles,California90073.AbstractThediscoveryofthesizeandcomplexityofthehumanmicrobiomehasresultedinanongoingreevaluationofmanyconceptsofhealthanddisease,includingdiseasesaffectingtheCNS.Agrowingbodyofpreclinicalliteraturehasdemonstratedbidirectionalsignalingbetweenthebrainandthegutmicrobiome,involvingmultipleneurocrineandendocrinesignalingmechanisms.Whilepsychologicalandphysicalstressorscanaffectthecompositionandmetabolicactivityofthegutmicrobiota,experimentalchangestothegutmicrobiomecanaffectemotionalbehaviorandrelatedbrainsystems.Thesefindingshaveresultedinspeculationthatalterationsinthegutmicrobiomemayplayapathophysiologicalroleinhumanbraindiseases,includingautismspectrumdisorder,anxiety,depression,andchronicpain.Ongoinglarge-scalepopulation-basedstudiesofthegutmicrobiomeandbrainimagingstudieslookingattheeffectofgutmicrobiomemodulationonbrainresponsestoemotion-relatedstimuliareseekingtovalidatethesespeculations.Thisarticleisasummaryofemergingtopicscoveredinasymposiumandisnotmeanttobeacomprehensivereviewofthesubject.CNSNeurolDisordDrugTargets.2014;13(8):1325-33.Implicationofgutmicrobiotainhumanhealth.KhanI,YasirM,AzharEI,KumosaniT,BarbourEK,BibiF,KamalMA1.Authorinformation• 1SpecialInfectiousAgentsUnit,KingFahdMedicalResearchCenter,KingAbdulazizUniversity,Jeddah,SaudiArabia.yasirkhattak.mrl@.AbstractGut-microbiota(GM)isconsideredahiddenmetabolicorganofthehumanbody,providingbiochemicalpathwayswhichareabsentinthehost.Balanceddietwithcalorierestriction(CR)promotesgrowthofhealthymicrobiota,leadingtolongevitybydown-regulatinginflammatoryresponses.While,dysbiosisleadstobodydysfunction,inducingmetabolicdisorders,causingpoorepithelialarchitecture,andimpedingthedevelopmentofmucosal-associatedlymphoidtissue,resultinginwithreducedTandBcellpopulations,renderingthebodypronetoinfections,cancerandallergy.TheGMenzymesactivityisanewriskfactorforcancerwhilegut-derivedinterleukin-6isassociatedwithhepatocellularcarcinomadevelopment.GMcanalsoinfluencethebrainbiochemistryandemotionalbehavior.ThealteredGMaffectsthegenesinvolvedinsecondmessengerpathwayandlong-termpotentiation,leadingtotheirdifferentialexpressioninthehippocampus,cortex,striatumandcerebellum.Inaddition,thedysbioticGMisassociatedwithautisticdisorder.LivingwithdysbioticGMispossiblewithconsequencesofseriousimpairments.BMCComplementAlternMed.2014Oct25;14:416.doi:10.1186/1472-6882-14-416.ProtectiveandrestorativepotencyofVitaminDonpersistentbiochemicalautisticfeaturesinducedinpropionicacid-intoxicatedratpups.AlfawazHA,BhatRS,Al-AyadhiL,El-AnsaryAK1Authorinformation1BiochemistryDepartment,ScienceCollege,KingSaudUniversity,P,Obox22452,Zipcode11495Riyadh,SaudiArabia.elansary@.sa.AbstractBACKGROUND:Reducingexposuretotoxicenvironmentalagentsisacriticalareaofintervention.Prenatalorpostnatalexposuretocertainchemicalshasbeendocumentedtoincreasetheriskofautismspectrumdisorder.Propionicacid(PA)foundinsomefoodsandformedasametabolicproductofgutmicrobiotahasbeenreportedtomediatetheeffectsofautism.Resultsfromanimalstudiesmayhelptoidentifyenvironmentalcontaminantsanddrugsthatproduceorpreventneurotoxicity,andmaytherebyaidinthetreatmentofneurodevelopmentaldisorderssuchasautism.Thepresentstudyinvestigatedtheprotectiveand/ortherapeuticeffectsofvitaminDagainstbrainintoxicationinducedbypropionicacid(PPA)inrats.METHODS:Twenty-eightyoungmaleWesternAlbinoratswereenrolledinthepresentstudy.Theyweregroupedintofourequalgroupsof7.Thecontrolgroupreceivedonlyphosphatebufferedsaline;theoralbufferedPPA-treatedgroupreceivedaneurotoxicdoseof250mg/kgbodyweight/dayfor3days;andtheVitaminD-protectedgroupreceived1000lU/kg/dayofalpha,25-dihydroxyvitaminD(3)(1,25-VD)fortwoweeks,afterwhichtheratswereinjectedwithPPA250mg/Kgbodyweight/dayfor3days.ThefourthgroupreceivedPPA250mg/Kgbodyweight/dayfor3daysfollowedbyalpha,25-dihydroxyvitaminD(3)(1,25-VD)fortwoweeks(VitaminDtherapeuticeffect).VitaminDandcalciumweremeasuredintheplasmaofthefourstudiedgroups.Serotonin,interferongamma(IFN-y),glutathione-s-transferaseactivityandDNAdoublehelixbreakswereassayedinthebraintissueoftheratsforallgroups.RESULTS:TheobtaineddatashowedthatthePPA-treatedgroupdemonstratedhigherplasmavitaminDlevelscomparedtothecontrolrats,togetherwithmultiplesignsofbraintoxicity,asindicatedbyadepletionofserotonin(5HT),anincreaseinIFN-yandinhibitionofglutathione-s-transferaseactivityasthreebiomarkersofbraindysfunction.Additionally,CometDNAassaysshowedremarkablyhighertaillength,tailDNA%damageandtailmomentasaneurotoxiceffectofPPA.CONCLUSIONS:VitaminDshowedagreaterprotectivethantherapeuticeffectonPPA-inducedneurotoxicityinrats,astherewasaremarkableameliorationoftheimpairedbiochemicallymeasuredparametersrepresentingneurochemical,inflammation,anddetoxificationprocesses.SeminImmunopathol.2015Jan;37(1):5-16.doi:10.1007/s00281-014-0456-2.Epub2014Oct22.Towardthecomprehensiveunderstandingofthegutecosystemviametabolomics-basedintegratedomicsapproach.AwW1,FukudaS.Authorinformation• 〔InstituteforAdvancedBiosciences,KeioUniversity,246-2Mizukami,Kakuganji,Tsuruoka,Yamagata,997-0052,Japan.AbstractRecentadvancesinDNAsequencingandmassspectrometrytechnologieshaveallowedustocollectmoredataonmicrobiomeandmetabolometoassesstheinfluenceofthegutmicrobiotaonhumanhealthatawhole-systemslevel.Majoradvancesinmetagenomicsandmetabolomicstechnologieshaveshownthatthegutmicrobiotacontributestohostoverallhealthstatustoalargeextent.Assuch,thegutmicrobiotaisoftenlikenedtoameasurableandfunctionalorganconsistingofprokaryoticcells,whichcreatestheuniquegutecosystemtogetherwiththehosteukaryoticcells.Inthisreview,wediscussindetailtherelationshipbetweengutmicrobiotaanditsmetaboliteslikecholine,bileacids,phenols,andshort-chainfattyacidsinthehosthealthandetiopathogenesisofvariouspathologicalstatessuchasmultiplesclerosis,autism,obesity,diabetes,andchronickidneydisease.Byintegratingmetagenomicandmetabolomicinformationonasystemsbiology-wideapproach,wewouldbebetterabletounderstandthisinterplaybetweengutmicrobiomeandhostmetabolism.Integrationofthemicrobiome,metatranscriptome,andmetabolomeinformationwillpavethewaytowardanimprovedholisticunderstandingofthecomplexmammaliansuperorganism.Throughthemodelingofmetabolicinteractionsbetweenlifestyle,diet,andmicrobiota,integratedomics-basedunderstandingofthegutecosystemisthenewavenue,providingexcitingnoveltherapeuticapproachesforoptimalhosthealth.JPediatrGastroenterolNutr.2010Oct;51(4):402-13.doi:10.1097/MPG.0b013e3181d75d52.Intrauterinegrowthrestrictionnotonlymodifiesthececocolonicmicrobiotainneonatalratsbutalsoaffectsitsactivityinyoungadultrats.Fan^a-BerthonP1.HoeblerC,MouzetE,DavidA,MichelC.Authorinformation• 1UMR1280,PhysiologiedesAdaptationsNutritionnelles,INRA,UniversitedeNantes,NantesAtlantiqueUniversites,Nantes,France.AbstractOBJECTIVE:Elucidatingwhyintrauterinegrowthrestriction(IUGR)predisposestosomeintestinalpathologieswouldhelpintheirprevention.Intestinalmicrobiotacouldbeinvolvedinthispredisposition;itsinitialsetupislikelytobealteredbyIUGRbecauseIUGRdelaysperinatalintestinaldevelopme