张发明Fecal microbiota transplantation through mid-gut for(2)

FecalmicrobiotatransplantationBCuietal.

Figure3Assessmentofin?ammationandimmunologyfunctionafterfecalmicrobiotatransplantation(FMT).(a)ThelevelofESRdecreasedonemonthpost-FMTrespectively,n=26,P<0.01;(b)CRPdecreasedoneweekpost-FMT,n=20,P<0.01;(c)SerumimmunoglobulinM(IgM)increasedsigni?-cantlyonemonthpost-FMT,n=18,P<0.01;(d–i)Tlymphocyte,CD3+CD4+cell,andratioofCD4+/CD8+wasincreasedatthreedayspost-FMT(P<0.05,respectively,n=14),whilethedifferenceofBlymphocyte,NKcells,andCD3+CD8+cellsbetweenbeforeandafterFMTtreatmentwerenotsigni?cant.

Table4ImpactfactorsonFMTef?cacy

Sixmonthspost-FMT

Clinicalimprovement(n)

Clinicalremission(n)66.7%(4/6)50%(12/24)0.656766.7%(4/6)50%(12/24)0.6567

66.7%(8/12)44.4(8/18)0.2839

56.5%(13/23)42.9%(3/7)0.6746

Donorandfecalbacteriainformation

Relativegeneticbackground

Closecontactwithrecipient

Ageofdonor(years)

Bacteriaform

yesnoPyesnoP≤14>14PfreshfrozenP66.7%(4/6)62.5%(15/24)1.000066.7%(4/6)62.5%(15/24)1.0000

75%(9/12)55.6%(10/18)0.4425

69.6%(16/23)42.9%(3/7)0.3717

Relativegeneticbackground:yes,brother,sisterorparent–childrelationshipsbetweendonorandrecipient;no,nogeneticrelationships.Fisher’sexacttestforallanalysis.

FMT,fecalmicrobiotatransplantation.

CD3+CD4+cells,Tlymphocyte,andratioofCD4+/CD8+threedayspost-FMTsigni?cantlyincreasedthanthosebeforeFMT.TheserumIgMlevelsalsoincreasedatonemonthpost-FMT.Theseimmunologicalchangesdemonstratedtheremodelingofgut?oraincreasedthehomeostaticimmunologicalabilitystatus.

TherehavebeenveryfewpossibleadverseeventsreportedforFMTtherapyintheliterature.26,27Consistently,thereisonlyveryminorpossibleadverseeventinthepresentstudy,suggestingFMTtherapyisarelativesafeprocedure.Spontaneousresolvedshort-56

termfeverinafewpatientsmaybea“doubtful”adverseeventrelatedtoFMT,whichhasbeenreportedbypreviousstudies.14,28AndseriousstricturesofcolonmightbeapotentialhighriskoffecalileusafterFMT.However,aneffectivehealtheducationandstrictinstructionondailyfoodmightbeimportanttosustaintheef?cacyofFMT.

Thepresentclinicalevidencesindicatedthatthegeneticrela-tionshiporclosecontactbetweenthedonorandpatients,theageofdonorwithintheselectedrangeandthedoseofbacteriawerenotassociatedwiththeef?cacyofFMT.However,thefreshfecal

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BCuietal.Fecalmicrobiotatransplantation

microbiotaappearedtohavehigherrateofclinicalimprovementandclinicalremissionthanfrozenmicrobiota.Butthiswasacaseseries;asmallsampleanalysismaynotbepowerfultodetectadifferenceinthedoseofbacteriaforFMT.

Thereareseverallimitationsinthispilotstudy.Itwasnotarigorousclinicaltrialdesignedtotestef?cacyofparticularFMTmethodologyversusanother.ThesubgroupofdiseaselocationrespondedtoFMTwerenotanalyzed.Instead,itwasanattempttostandardizeFMT,astheprocedureprotocolevolvedinthecourseofourclinicalexperience.Amulticenterrandomizedclinicaltrialwithlargersamplesizewouldbeimportanttoprovidemoreevi-dences.Longerfollow-upisnecessaryforassessmentofsafetyandef?cacy.Endoscopyevaluationwasnotperformedforeachcasewithinsix-monthfollow-upbecauseofpotentialrisk.Wearecurrentlytryingtoidentifythebacteriaspecieswhicharethera-peuticallymostimportanttopatientsbycharacterizingthemicro-bialcompositionofdonormaterialandrecipients’fecalsamplescollectedduringfollow-up.

Inconclusion,thisisapilotstudywiththelargestsampleofpatientswithrefractoryCDwhounderwentstandardizedsingleFMTthroughmid-gut.Thisstudyreportedanewstandardizedlaboratoryprotocolandspeci?cclinicalwork?ow.Thestrengthliesinthatthisstudyevaluatedserialobjectiveendpointsandoutcomesapartfromclinicalremissionwhichincludedbiochemicalimprove-ment,weight,andmarkersofimmunesystem.Theresultsdemon-stratedthatstandardizedFMTthroughmid-gutmightbeasafe,feasible,andef?cientrescuetherapyforrefractoryCD.

Acknowledgment

ThisstudywassupportedbypublicdonatedIntestineInitiativeFoundation,ClinicalScienceandTechnologyFoundationofJiangsuProvince(BL2014097)andtheNationalScienceandTechnologyMajorProject(2012BAI06B03).

References

1BorodyTJ,KhorutsA.Fecalmicrobiotatransplantationand

emergingapplications.Nat.Rev.Gastroenterol.Hepatol.2012;9:88–96.

2QinJ,LiR,RaesJetal.Ahumangutmicrobialgenecatalogueestablishedbymetagenomicsequencing.Nature2010;464:59–65.3ShaS,XuB,WangXetal.Thebiodiversityandcompositionofthedominantfecalmicrobiotainpatientswithin?ammatoryboweldisease.Diagn.Microbiol.Infect.Dis.2013;75:245–51.

4NgSC,BenjaminJL,McCarthyNEetal.Relationshipbetweenhumanintestinaldendriticcells,gutmicrobiota,anddiseaseactivityinCrohn’sdisease.In?amm.BowelDis.2011;17:2027–37.5AndersonJL,EdneyRJ,WhelanK.Systematicreview:faecal

microbiotatransplantationinthemanagementofin?ammatoryboweldisease.Aliment.Pharmacol.Ther.2012;36:503–16.

6FrankDN,StAmandAL,FeldmanRA,BoedekerEC,HarpazN,PaceNR.Molecular-phylogeneticcharacterizationofmicrobial

communityimbalancesinhumanin?ammatoryboweldiseases.Proc.Natl.Acad.Sci.U.S.A.2007;104:13780–5.

7CosnesJ,CattanS,BlainAetal.Long-termevolutionofdiseasebehaviorofCrohn’sdisease.In?amm.BowelDis.2002;8:244–50.8LichtensteinGR,FeaganBG,CohenRDetal.SeriousinfectionsandmortalityinassociationwiththerapiesforCrohn’sdisease:TREATregistry.Clin.Gastroenterol.Hepatol.2006;4:621–30.

9AngelbergerS,ReinischW,MakristathisAetal.Temporalbacterialcommunitydynamicsvaryamongulcerativecolitispatientsafterfecalmicrobiotatransplantation.Am.J.Gastroenterol.2013;108:1620–30.

10KhorutsA,SadowskyMJ.Therapeutictransplantationofthedistal

gutmicrobiota.Mucosal.Immunol.2011;4:4–7.

11SmitsLP,BouterKE,deVosWM,BorodyTJ,NieuwdorpM.Therapeuticpotentialoffecalmicrobiotatransplantation.Gastroenterology2013;145:946–53.

12ZhangF,LuoW,ShiY,FanZ,JiG.Shouldwestandardizethe

1700-year-oldfecalmicrobiotatransplantation.Am.J.Gastroenterol.2012;107:1755–6.

13SurawiczCM,BrandtLJ,BinionDGetal.Guidelinesfordiagnosis,

treatment,andpreventionofClostridiumdif?cileinfections.Am.J.Gastroenterol.2013;108:478–98.

14vanNoodE,VriezeA,NieuwdorpMetal.Duodenalinfusionof

donorfecesforrecurrentClostridiumdif?cile.N.Engl.J.Med.2013;368:407–15.

15ShaS,LiangJ,ChenMetal.Systematicreview:faecalmicrobiota

transplantationtherapyfordigestiveandnondigestivedisordersinadultsandchildren.Aliment.Pharmacol.Ther.2014;39:1003–32.16ZhangFM,WangHG,WangM,CuiBT,FanZN,JiGZ.Fecal

microbiotatransplantationforsevereenterocolonic?stulizingCrohn’sdisease.WorldJ.Gastroenterol.2013;19:7213–6.17KaoD,HotteN,GillevetP,MadsenK.FecalMicrobiota

TransplantationinducingremissioninCrohn’scolitisandthe

associatedchangesinfecalmicrobialpro?le.J.Clin.Gastroenterol.2014;48:625–8.

18GordonH,HarbordM.ApatientwithsevereCrohn’scolitis

respondstofaecalmicrobiotatransplantation.J.CrohnsColitis2014;8:256–7.

19RizzelloF,GionchettiP,VenturiA,MorselliC,CampieriM.Reviewarticle:themanagementofrefractoryCrohn’sdisease.Aliment.Pharmacol.Ther.2002;16(Suppl.4):40–7.

20MacDermottRP.Treatmentofirritablebowelsyndromeinoutpatientswithin?ammatoryboweldiseaseusingafoodandbeverageintolerance,foodandbeverageavoidancediet.In?amm.BowelDis.2007;13:91–6.

21VermeireS,SchreiberS,SandbornWJ,DuboisC,RutgeertsP.CorrelationbetweentheCrohn’sdiseaseactivityand

Harvey–BradshawindicesinassessingCrohn’sdiseaseseverity.Clin.Gastroenterol.Hepatol.2010;8:357–63.

22TremaroliV,BackhedF.Functionalinteractionsbetweenthegutmicrobiotaandhostmetabolism.Nature2012;489:242–9.23NicholsonJK,HolmesE,KinrossJetal.Host-gutmicrobiotametabolicinteractions.Science2012;336:1262–7.

24HamerHM,JonkersD,VenemaK,VanhoutvinS,TroostFJ,BrummerRJ.Reviewarticle:theroleofbutyrateoncolonicfunction.Aliment.Pharmacol.Ther.2008;27:104–19.

25PanaccioneR,LoftusEVJr,BinionDetal.Ef?cacyandsafetyofadalimumabinCanadianpatientswithmoderatetosevereCrohn’sdisease:resultsoftheAdalimumabinCanadianSubjectswithModEratetoSevereCrohn’sDiseaSe(ACCESS)trial.Can.J.Gastroenterol.2011;25:419–25.

26DeLeonLM,WatsonJB,KellyCR.Transient?areofulcerative

colitisafterfecalmicrobiotatransplantationforrecurrentClostridiumdif?cileinfection.Clin.Gastroenterol.Hepatol.2013;11:1036–8.27QueraR,EspinozaR,EstayC,RiveraD.Bacteremiaasanadverse

eventoffecalmicrobiotatransplantationinapatientwithCrohn’sdiseaseandrecurrentClostridiumdif?cileinfection.J.CrohnsColitis.2013;8:252–3.

28KundeS,PhamA,BonczykSetal.Safety,tolerability,andclinicalresponseafterfecaltransplantationinchildrenandyoungadultswithulcerativecolitis.J.Pediatr.Gastroenterol.Nutr.2013;56:597–601.

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Supportinginformation

AdditionalSupportingInformationmaybefoundintheonlineversionofthisarticleatthepublisher’sweb-site:

FigureS1Studydesignandproceduresinvolvedintheresearch.TableS1InclusionandexclusioncriteriaforrefractoryCDintheTableS2Exclusioncriteriaofdonorforstool.

TableS3Scheduleandprotocolofstandardizedfecalmicrobiotatransplantataion.

presentstudy.

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