张发明Fecal microbiota transplantation through mid-gut for

bs_bs_bannerdoi:10.1111/jgh.12727

CLINICALTRIALSANDTHERAPEUTICS

Fecalmicrobiotatransplantationthroughmid-gutfor

refractoryCrohn’sdisease:Safety,feasibility,andef?cacytrialresults

BotaCui,*,1QiangFeng,?,1HonggangWang,*,MinWang,*ZhaoyuanPeng,*PanLi,*

GuangmingHuang,*ZhengLiu,*PingWu,*ZhiningFan,*GuozhongJi,*XinWang,?KaichunWu,?DaimingFan?andFamingZhang*

*MedicalCenterforDigestiveDiseases,theSecondAf?liatedHospitalofNanjingMedicalUniversity,Nanjing,?BGI-Shenzhen,Shenzhen,?StateKeyLaboratoryofCancerBiology&XijingHospitalofDigestiveDiseases,FourthMilitaryMedicalUniversity,Xi’an,China

1

Keywords

Crohn’sdisease,fecalmicrobiota

transplantation,in?ammatoryboweldisease,rescuetherapy.

Acceptedforpublication12August2014.Correspondance

ProfFamingZhang,MedicalCenterforDigestiveDiseases,theSecondAf?liatedHospitalofNanjingMedicalUniversity,121JiangJiayuan,Nanjing210011,China.Email:fzhang@njmu.edu.cn

1

Abstact

BackgroundandAim:Thegutmicrobiotaplaysapivotalroleintheintestinaldiseases.Fecalmicrobiotatransplantation(FMT)mightbearescuetherapyforrefractoryin?am-matoryboweldisease.Thisstudyaimedtoevaluatethesafety,feasibility,andef?cacyofFMTthroughmid-gutforrefractoryCrohn’sdisease(CD).

Methods:Weestablishedstandardizedlaboratoryprotocolandclinicalwork?owforFMT.OnlyrefractoryCDpatientswithHarvey–BradshawIndex(HBI)score≥7wereenrolledforthisstudy.AllincludedpatientsweretreatedwithsingleFMTthroughmid-gutandassessedduringfollow-up.

Results:Metagenomicsanalysisshowedahighconcordancebetweenfecessampleandpuri?edfecalmicrobiotafromsamedonors.Standardizedfecalmicrobiotapreparationandclinical?owsigni?cantlysimpli?edthepracticalaspectsofFMT.Totally,30patientswerequali?edforthepresentanalysis.Therateofclinicalimprovementandremissionbasedonclinicalactivityatthe?rstmonthwas86.7%(26/30)and76.7%(23/30),respectively,whichwashigherthanotherassessmentpointswithin15-monthfollow-up.Patients’bodyweightincreasedafterFMT,andthelipidpro?leimprovedaswell.FMTalsoshowedafastandcontinuoussigni?canteffectinrelievingthesustainingabdominalpainassociatedwithsustainingCD.

Conclusion:ThisisapilotstudywiththelargestsampleofpatientswithrefractoryCDwhounderwentsingleFMT.TheresultsdemonstratedthatFMTthroughmid-gutmightbeasafe,feasible,andef?cientrescuetherapyforrefractoryCD.

Theseauthorscontributedequallytothiswork.

Partialresultsofthepresentstudywere

orallypresentedintheconferenceofJournalofGastroenterology&HepatologyFoundation(JGHF)YoungInvestigatorAward(YIA)inGastro2013APDW/WCOGShanghai(O0018).

Theauthorshavenocon?ictsofinteresttodisclose.

Introduction

Thegutmicrobiotaisconsideredtoconstitutea“microbialorgan”whichplaysapivotalroleintheintestinaldiseases.1Thegutmetagenomicsequencingshowedthatover99%ofthegenesarebacterial.2Previousstudiesfromourgroup3andothers4,5stronglysupportthelinkbetweenintestinalbacteriaandin?ammatoryboweldisease(IBD).IBDisachronicin?ammatorydisorderofthegastrointestinaltractthatincludesbothulcerativecolitis(UC)andCrohn’sdisease(CD).InIBDpatients,theadaptiveimmunesystemishyper-reactivetothecommensalintestinalmicro?oraingeneticallysusceptibleindividuals,andtheintestinal?oraspeciesdecreasesbyabout30?50%.6

JournalofGastroenterologyandHepatology30(2015)51–58

PatientswithsevereCDusuallypresentwithsystemicsymp-tomssuchasabdominalpain,diarrhea,fatigue,anorexia,andmalnutrition,sometimeswithstricturing,?stula,orperforatingcomplications.7TheconventionalapproachforCDtreatmentisadministrationofmultiplecoursesofcorticosteroidsandimmunomodulatorspriortoescalationtomonoclonalanti-bodies,whiletherearemanydisadvantagesofthesedrugs.8AlternativeCDtreatmentapproachesaimedatmodifyingthecompositionoftheintestinalmicrobiotainordertoovercomegutdysbiosishavebecomeamajorinterestinrecentyears.9TransplantationofthefecalmicrobiotafromhealthydonorsisoneofthepotentialalternativetherapyoptionsforIBD.1,9–11

51

?2014JournalofGastroenterologyandHepatologyFoundationandWileyPublishingAsiaPtyLtd

FecalmicrobiotatransplantationBCuietal.

Theconceptoffecalmicrobiotatransplantation(FMT)fortreat-mentofhumanintestinaldiseaseswas?rstlyrecordedintradi-tionalChinesemedicine(TCM)inthefourthcentury.12Inmodernmedicine,FMThasbeenusedforsuccessfullytreatingthousandsofcaseswithClostridiumdif?cileinfection13,14andlimitedcaseswithIBD.9Alldocumented12reportsofFMTforIBDuntilMay2013haddemonstratedasuccessratecloseto90%inimprovingUC15buthadbeenrarelyusedforCDmanagement.15Recently,threeseparatecasesshowedthatclinicalremissionswereachievedbyFMTinthreesevereCDpatients.16–18Onewasreportedbyusaboutapatientwithsevereentercolonic?stulizingCrohn’sdisease.16Thiscasehassustainedclinicalremissionwithnormalworkproductivityoveroneyear,andthefollow-upisongoing.However,despitethelongandsuccessfultrackrecord,aswellasgreatclinicalneed,theavailabilityofFMTformanypatientsremainsverylimitedduetounstandardizedprocedureforIBDandlackofsystemicclinicalstudyaswellasthebasicresearch.In2012,weestablishedthestandardizedFMTprogram,whichhasevolvedsincetoovercomeorminimizesomeoftheassociatedchallengesinisolationofgut?oraandclinicalwork?ow.Thisstudyexploredthesafety,feasibility,andef?cacyofsinglestan-dardizedFMTthroughmid-gutfortreatmentofrefractoryCD.torypuri?edfreshfecalmicrobiotasuspensionwasinputintopatients’mid-gutbyatubewithingastroscopeunderanesthesia,andtheentireprocedureshouldbedonewithin1h.Ifthefecalmicrobiotawasobtainedfrombacteriabankunder?80°C,itshouldbethawedatroomtemperature?rstandthenproceedtoFMTimmediately.AfterFMT,patientswereencouragedtoeataccordingtofoodinstructionmadebyus,whichwasbasedontheliteraturebyMacdertmott.20Mesalazine3.0gdailywasgivenasasustaintreatmentforthreemonthsandthenthedosereducedto1.5–2.5gdaily,noothermedicationwasused.Althoughmesalazinehadlimitedbene?tinmoderatetosevereCD,thereasonforusingherewastoprovideadjunctiveanti-in?ammationeffectforthepatientswhomightachieveimprovementtowildconditionorgetremissionafterFMT.Toavoidtheobservationbias,MesalazinewasstartedfromoneweekbeforeFMT.BloodandstoolsampleswerecollectedbeforeandafterFMT.

Here,weinputthemicrobiotabymid-gutinsteadofduodenum,itisbecauseofthepossiblerouteviaduodenumbelowVaterpapilla,orproximaljejunumpost-gastrodunodenalsurgery.Theendoscopicparameterswerecollected,includingthetimeofinjectingbacteriasuspension,whethertherewasre?uxfromsmallintestinetostomachandotheradverseevents.

Methods

Patientrecruitment.Allpatientsanddonorsagreedtopar-ticipateinaclinicaltrialofFMTformoderatetosevereCD(NCT01793831)atTheSecondAf?liatedHospitalofNanjingMedicalUniversity.StandardizedFMTwasofferedtopatients,whomhadtoberefractorytostandardCDtreatmentoptions.Atpresenttime,thereisnoagreementonde?nitionofrefractoryCD.19Tode?netherefractoryCD,wehadmadedetailedstan-dards,andpatientswereincludedorexcludedaccordingTableS1.ThestudystartedNovember2012,andtheendpointoffollow-upwasFebruary2014.

Donorscreening.Patientswereaskedtoself-identifypoten-tialdonor,suchasrelative,familymember,friend,orthephysicianrecommendedfecalmicrobiotafromourbacteriabank.Acom-pletemedicalandsurgicalhistoryofeachpotentialdonorwasobtained.Donorswereconsideredtobesuitableiftheyhadbeenscreenedbyourexclusioncriteria(TableS2).Theageofdonorrangedfrom8to15-yearolds,exceptonewhowas28yearsold.Eightpatientsshareddonorswithothersbecausetheycouldn’tsupplyavaliddonorthemselves.ThevolunteerswhohadpassedtheselectioncriteriaweregiventwobagsofForlax(macrogol4000)orallybeforedefecation.

PatientpreparationandFMTprocedure.AsshowninTableS3,atleastoneweekpriortoFMT,allconventionaltreat-mentforCDwasstopped.BeforeFMT,patientconditionwasassessedthoroughly,includingdiseaseduration,diseaselocaliza-tion,diseasebehavior,treatmentandsurgicalhistory,bodyweight,aswellasHarvey–BradshawIndex(HBI).Peripheralbloodwascollectedforchemicalandbiologicalanalyses.Patientswerepre-paredaccordingtothepreparationofcustomgastroscopy.ThedetailedprocedureofFMThadbeenshowninTableS3.Labora-52

StoolsamplecollectionandmicrobialDNAextraction.Fecalsampleswereobtainedfromfourclinicalscanneddonors(TableS2)aftersigninganinformedconsentform,andwereisolatedformicrobiotaatthelaboratory.ThefecalsamplesandisolatedmicrobiotasampleswerefrozenimmediatelyandunderwentDNAextractionusingstandardmethodsatBGI-Shenzhen.2Forsequencinganddataprocessing,IlluminaGAIIx&HiSeq2000(SanDiego,CA)wereused.2

SurveillancepostFMT.ThewholeprocessofthisstudywasshowninFigureS1.Thesurveillancepointsstartedfromthe?rstdaytothethirdday,oneweek,onemonth,threemonths,andlatereverythreemonthsafterFMT.TheactivityofthediseasewasassessedbyHBIbaseduponabdominalsymptoms,examination?ndings,andpresenceofextraintestinalmanifestations.21Clinicalimprovementwasde?nedasdecreaseofHBI>3.Clinicalremis-sionwasde?nedasHBIscore≤4.Allthepatientswhoachievedclinicalremissionwerealsoincludedintheanalysisofclinicalimprovement.Bloodandstoolsampleswerecollectedatthesametimeandwereanalyzedby?owcytometryandlaboratoryexami-nation,clinicalactivitywasalsoassessedateachvisit.Forthosepatientslivinginremoteprovinces,somefollow-upinformationwasobtainedthroughtelephoneandInternet.Thesurveillancewasstoppedincaseofdiseaserecurrenceorgettingworse.

Safety.AdverseeventswererecordedduringFMTandafterFMT.Forassessmentoflongertermsafety,allinvolvedpatientshadmorethansixmonthsoffollow-up.IntensityandrelationshipofadverseeventswithFMTwasdescribedusingCommonTermi-nologyCriteriaforAdverseEvents(version3.0).Intensityofadverseeventswasclassi?edasmild,moderate,severe,ordis-abling.RelationshipofadverseeventswithFMTwascategorizedasunrelated,possible,probable,orde?nitelyrelatedtoFMT.

JournalofGastroenterologyandHepatology30(2015)51–58

?2014JournalofGastroenterologyandHepatologyFoundationandWileyPublishingAsiaPtyLtd

BCuietal.Fecalmicrobiotatransplantation

Statisticalanalysis.DatawereanalyzedbyusingSPSS(Chicago,IL)orGraphPad(LaJolla,CA).Analysesincludedpairedstudent’st-testforpaireddataandFisher’sexacttestforcategoricaldata.TwotailedPvaluewascalculatedwitheachtest.Pvalues<0.05wereconsideredsigni?cant.

Ethicalconsiderations.Thisclinicalstudy(NCT01793831)hadbeenapprovedbytheSecondAf?liatedHos-pitalofNanjingMedicalUniversityethicalcommitteeinNovem-ber2012.Allpatientsanddonorswereinformedofthebene?tsandpotentialrisksofstandardizedFMTandlaboratoryscreening.Theirwritteninformedconsentwasobtained.

withmetoclopramidewaslowerthanthatingroupwithoutmetoclopramide(P<0.05,datanotshown).Theeffectofmetoclopramidemightpotentiallyavoidtheadverseeventsduringprocedure,suchasvomitingduringendoscopy,adverseeventsafterlongertimeanesthesia.Two(2/30)patientswereobservedwithfeverwithin1hto6hafterFMT.Thiswasconsideredasdoubtfuladverseevent,becausethesepatientsalsohadfeveraftertheircolonoscopyunderanesthesiabeforeFMT.Within1hto6hafterFMT,23.3%(7/30)ofpatientshadincreaseddiarrhea.Althoughnopainandfecalileusoccurred,thecriteriahadtobementionedthatthosepatientswithseverestrictureinrectumwere

Results

Patientanddonorcharacteristics.Thisstudyincludes49patientswhoreceivedstandardizedFMTthroughmid-gutforCD.AllpatientswereChineselivinginChina.Nineteenpatientswereexcludedfromanalysis,including11patientswithlessthansix-monthfollow-up,threepatientswithstoma,threeforunde-?nedIBD,oneforaccompanyingwithglycogenstoragedisease,andoneforC.dif?cileinfection.Finally,30patientswereana-lyzedinthisstudy(Table1).Scannedforstooldonationwere23donors.

Sequencingofpuri?edfecalmicrobiotaandfeces.Theshotgunsequencingjusti?edthesimilarityofbacte-rialcompositionbetweenthepuri?edfecalmicrobiotaandoriginalfecesfromfourdonors(Fig.1).Thepuri?edfecalmicrobiotaseemedhigherthanthatoforiginalfeces,whiletherewasnosigni?cantdifference.Thisindicatesthatpuri?cationoffecalmicrobiotashouldbeagoodwaytoenrichbacteriaforhavingsensitivesequencingresults.ThemappingratetomOTUdatabasewashigherthanthatoforiginalfeces.Thisindicatesthatthepuri?edfecalmicrobiotashouldbequitesimilarbutlesscomplexthanoriginalfeces.

SafetyofFMTandendoscopicprocedure.Therewerenosevereorobviousadverseeventsduringendoscopicinfu-sionafterFMTandlong-termfollow-up.Theinjectionofmetoclopramidesavedthetimeofendoscopicinfusion(3.5±2.16minvs6.0±1.23min,P=0.0192).Therateof?orasuspensionre?uxfromduodenumtostomachingroup

Table1ThecharacteristicsofincludedpatientsanddonorsItems

Results

30

38.0±13.83(15–71)64.5(19)7.4±5.311.7±4.526.7%(8)10%(3)63.3%(19)48.8±10.166.7%(20)56.7%(17)20%(6)60%(18)2011

23

14.3±5.2(5–28)56.5(13)26.1%(6)26.1%(6)

Patient

Totalnumber

Age,m±SD(range)Sex,male%(n)

Diseaseduration(years,m±SD)HarveyBradshawIndex(m±SD)Location,%(n)

L1(withorwithoutp)L2(withorwithoutp)L3(withorwithoutp)Weight(kg,m±SD)

Usingimmunomodulator,yes%(n)Usingsteroid(>10mg/dprednisoneequivalent),yes%(n)Usinganti-TNF,yes%(n)

Withhistoryofsurgery,yes%(n)Frequencyofsurgery(n)IntestinalsurgeryAnalsurgeryTotalnumber

Age,m±SD(range)Sex,male%(n)

Onedonorto≥2recipients,%(n)Geneticbackground,yes%(n)

Donor

Immunomodulatorheredidnotincludesteroid.

Geneticbackgroundwithrecipient:yes,withbrother,sisterorparent-childrelationshipbetweendonorandrecipient.

L1,ileal;L2,colonic;L3,ileocolonic;P,perianaldisease(accordingtoMontrealclassi?cationofCD).

Figure1Metagenomicsanalysis.(a)ThespeciesnumberofbacteriawasevaluatedbypairedWilcoxtest,andtheresultsshowedthattherewerenosigni?cantdifferencesbetweenthepuri?edfecalmicrobiotaandoriginalfecesfromfourdonors.(b)ThemappingratetomOTUdatabasebetweentwogroupsfurthersupportedthesimilarity.Thefecessample(n=4)andpuri?edmicrobiotasamples(n=4)werefromfourhealthydonors.,puri?ed;,fecal.

JournalofGastroenterologyandHepatology30(2015)51–58

?2014JournalofGastroenterologyandHepatologyFoundationandWileyPublishingAsiaPtyLtd

53

FecalmicrobiotatransplantationBCuietal.

excludedforFMT.Exceptoftheabove,therewerenomoreadverseeventsduringthewholeFMTprocedureand6–15-monthfollow-up.

ResponsetoFMT.CD-relatedabdominalpain,stoolfre-quency,bloodypurulentstool,erythrocytesedimentationrate(ESR),C-reactiveprotein(CRP),?stula,andotherparameterswereassessedforallpatientsafterFMT.Endoscopy,magneticresonanceimagingorcomputedtomographyscanwasgenerallyperformedsixmonthsafterFMT.HBIateachassessmentpointfromoneweekpost-FMTdramaticallydecreasedcomparedwiththebaselineHBIbeforeFMT(Fig.2).Bothratesofclinicalimprovement(86.70%)andclinicalremission(76.7%)reachedthepeakof15-monthfollow-upatthe?rstmonthpost-FMT.Thelongestfollow-upuntiltheendpointofthisstudywas15months,andtheshortestfollow-upincludedinthisanalysiswas6months(Table2).Thosepatientsweren’tinvolvedinlaterassessmentforhavingnotreachedtherequiredassessmenttimepoint.Twenty-sixof30patientshadabdominalpainorrelatedbackpain(de?nedasCD-relatedpain).Figure2showedanimmediatesigni?cantreliefatseveralhourspost-FMT.Andbodyweightincreasedsigni?-cantlyatthree-monthassessmentpointafterFMT.

AsshowninFigure3a–c,thelevelofESRdecreasedonemonthpost-FMTcomparedwiththevaluebeforeFMT(n=27,P<0.01),CRPinperipheralblooddecreasedat1weekafterFMT(n=20,P<0.01),andtheserumimmunoglobulinM(IgM)increasedsigni?cantly1monthafterFMT(n=18,P<0.01).Bloodlymphocytesof17patientswereanalyzedbyFCMatlaterphase.Threepatientswereexcludedfromtheanalysisforhavingbeentreatedwithimmunomodulatorsorsteroidwhenpresentedtoourhospital,whichmaydisturbthenormallymphocytesystem.AsshowninFigure3d–i,Tlymphocyte,CD3+CD4+cell,andratioofCD4+/CD8+wasincreasedatthreedayspost-FMT(P<0.05,n=14),whiletherewerenosigni?cantchangeinBlymphocyte,NKcells,andCD3+CD8+cellsbeforeandafterFMTtreatment.Changesofbloodbiochemistry.Plasmahemoglobin,albumin,andbloodlipidwereanalyzed(Table3).ThreemonthsafterFMT,thelevelofplasmahemoglobin,albumin,totalcholes-terol,HDL-C,andLDL-Callshowedsigni?cantincreasecom-paredwiththatbeforeFMT(P<0.05).

FMT-relatedfactors.Wetestedthecorrelationbetweenthepotentialimpactfactors(includingdonors’age,relativegeneticbackground,orclosecontactwithrecipients,fecalbacteria’sform)andpatients’clinicalresponseatsixmonthspost-FMT.AsseeninTable4,relativegeneticbackgroundorclosecontactwithrecipi-entsdidnotsigni?cantlyaffecttheoutcomeofpatients’clinicalresponseatsixmonthsafterFMT.Therewerenodifferencesinpatients’clinicalresponsebetweenthetwoagegroupsofdonors,whichweredividedbythemeanageofdonors(14-yearolds).Theef?cacyofFMTusingfreshfecalmicrobiotaseemedhigherthanthatusingfrozenfecalmicrobiota,however,thedifferenceontheclinicalimprovementorclinicalremissionwasnotsigni?cantly.

Discussion

Theintestinalmicrobiotaplaysimportantrolesintheregulationofhumanphysiology,2includemetabolism,nutritionabsorption,and

54

Figure2Harvey–BradshawIndex(HBI)scoreanalysisandabdominalpainremission.(a)TheHBIscoreatthebaselinebeforefecalmicrobiotatransplantation(FMT),andsurveillancepointat?rstweekand?rstmonthpost-FMT.(b)Thechangeofpatients’HBIscoresfrombasicvaluebeforeFMTto15monthspost-FMTduringthefollow-up.(c)FMTrelievedabdominalpain(n=26)andsustainedtheeffects(trendoflongerfollow-upthanonemonthnotshown),fourcaseswithoutpainbeforeandafterFMTwerenotincluded.

JournalofGastroenterologyandHepatology30(2015)51–58

?2014JournalofGastroenterologyandHepatologyFoundationandWileyPublishingAsiaPtyLtd

BCuietal.Fecalmicrobiotatransplantation

Table2ClinicalresponsetoFMT

Post-FMT1week1month3month6month9month12month15month1month3month6month

Clinicalimprovement(n)83.3%(25/30)86.7%(26/30)80%(24/30)66.7%(20/30)57.1%(12/21)60%(9/15)85.7(6/7)

48.9±10.1vs49.9±10.2*(30)48.3±9.9vs50.1±11.3*(23)48.8±9.9vs51.8±10.9**(22)

Clinicalremission(n)60%(18/30)76.7%(23/30)70%(21/30)60%(18/30)52.3%(11/21)53.3%(8/15)57.1(4/7)///

ClinicalresponseActivitybasedHBI

Bodyweight(beforevspost)

Pairedt-test,*P<0.05,**P<0.001.

ThecomparisonofHBIbetweenpost-FMTineachobjectiveendpointfromoneweekto15monthsandbaselineissigni?cantly(pairedt-test,P<0.005,datanotshowninthistable).Theratesofclinicalimprovementincludethepatientswhoachievedclinicalremission.Bodyweight(mean±SD).

FMT,fecalmicrobiotatransplantation;HBI,Harvey–BradshawIndex.

Table3ChemicalchangesafterFMTduringfollow-up

n242418181818

BeforeFMT101.0±23.0932.95±8.963.29±1.011.26±0.820.98±0.281.78±0.63

3monthspost-FMT114.0±21.8038.83±7.953.67±0.771.54±0.851.15±0.302.02±0.51

P0.0016**0.0067**0.0327*0.29340.048*0.0066**

Parameter(normalrange)Hemoglobin(110–160,g/L)Albumin(39.7–49.4,g/L)

Totalcholesterol(3.0–5.7mmol/L)Triglycerides(0.4–1.7mmol/L)HDL-C(1–23.1mmol/L)LDL-C(<3.1mmol/L)

*P<0.05;**P<0.01.

Pairedt-test,thevalue(mean±SD)ofeachassessmentpointafterFMTcomparedwiththatbeforeFMT.

FMT,fecalmicrobiotatransplantation;HDL-C,highdensitylipoprotein-cholesterol;LDL-C,lowdensitylipoprotein-cholesterol.

immunologicalreaction.22–24Here,weestablishedanewstandard-izedFMTprotocoltorebuildrefractoryCDpatientsintestinalmicrobiotacircumstance,includingthecrudepuri?cationofmicrobiotafromfeces,preparationofrecipientbeforetransplan-tation,endoscopicprotocolthroughmid-gut,volumeofpuri?edmicrobiotaforasingletherapy,andthefoodplanbeforeandaftertheFMT.

Shotgunsequencingshowedthatthismethodsuccessfullymaintainedthebacteriacompositioninthepuri?edmicrobiotacomparedwiththeoriginalfecesmicrobiota.Theselected30casesinthisstudyhadfailedorhadbeenprovennotsuitabletobiotherapeutics,immunosuppressant,steroids,aminosalicylicacid,orsurgery.AfterFMTtreatment,theoverallclinicalimprove-mentandclinicalremissionofthesecaseswas83.3%and60%atthe?rstweek,respectively.ThisstronglyshowedthefastclinicalresponsetoFMTthroughmid-gut.Thehighestratesofclinicalimprovement(86.7%)andclinicalremission(76.7%)afterFMTwereatthe?rstmonth.Thefollow-upwithinthe15monthsfurthershowedthesustainedclinicalef?cacy.Thereasonwhythehighestef?cacyappearedat?rstmonthpost-FMTremainedunknown.Furthermetagenomicanalysiswithpatients’fecesmicrobiotawillprovidemoreevidences.Apossibleexplanationwasthehostintes-tinemayexertcolonizationresistancetothetransplantedmicrobiotaatbeginning,afteronemonth’sremodeling,anewbalancewasrebuiltbetweentheforeignmicrobiotaandhost

JournalofGastroenterologyandHepatology30(2015)51–58

microbiota,whichwouldexertmaximalef?cacy.Butthebalancemightbevulnerabletotheeffectofhost’sgenetic,intestinalenvi-ronment,dietary,andotherpathogenesis,whichmightultimatelycausethediseaserelapse.

OneofaimsoftherapyforCDistoregainworkandproduc-tivityimprovement.25FMTtherapysigni?cantlyimprovedthepro-ductivityoutsideofworkinthepresentpopulationofpatients.Unfortunately,theworkabilitywasnotincludedforassessment.Themoresurprising?ndinginthisstudywastheroleofFMTthroughmid-gutinrelievingCD-relatedpain,whichusedtobeaclinicallychallengeforaphysician.Althoughtheresultshouldbecon?rmedbyalargeplacebogroup,thisimpliedde?nitelynovelcluesontranslationalresearchfromgut?oraremodelingtopainmanagement.

Thebodyweights,aswellasthehemoglobin,albumin,andlipidpro?leofpatientswithCDwereimprovedafterFMT.Oftheinvolvedpatients,35.5%(11/30)haddry,itchy,orburstskin,whichwasde?nedas“skinlesions,”72.7%(8/11)ofthemhadlesionsrelievedwithintwoweeksafterFMT(datanotshown).Sevenin10patientswhohadsexuallifewerereportedtohavesigni?cantimprovementinthequalityofsexuallifeinthreemonthsafterFMT(datanotshown).TheseinterestingphenomenonamightrelatetotheimprovementofnutritionstatusafterFMT.

ThedecreasedCRPandESRoneweekpost-FMTshowedthefastanti-in?ammationeffect.FCMtestdemonstratedthe

55

?2014JournalofGastroenterologyandHepatologyFoundationandWileyPublishingAsiaPtyLtd

百度搜索“77cn”或“免费范文网”即可找到本站免费阅读全部范文。收藏本站方便下次阅读，免费范文网，提供经典小说综合文库张发明Fecal microbiota transplantation through mid-gut for在线全文阅读。