AnnetteFritscher-Ravens,1DetlefSchuppan,2,3,4MarkEllrichmann,1StefanSchoch,1ChristophR?cken,5JochenBrasch,6JohannesBethge,1MartinaB?ttner,7JuliusKlose,andPeterJ.Milla8
1UnitofExperimentalEndoscopy,DepartmentofInternalMedicineI,5DepartmentofPathology,6DepartmentofDermatology,74UniversityHospitalSchleswig-Holstein,Kiel,Germany;2InstituteofTranslationalImmunology,DepartmentofMedicineI,ResearchCenterforImmunology,UniversityofMainz,Mainz,Germany;4DivisionofGastroenterology,BethIsraelDeaconess76MedicalCenterandHarvardMedicalSchool,Boston,Massachusetts;7DepartmentofAnatomy,ChristianAlbrechtUniversity,77Kiel,Germany;8UCLInstituteofChildHealth,UniversityCollegeLondon,London,UnitedKingdom
背景目标：研究疑似食物耐受不良的IBS患者，使用共聚焦激光显微内镜（CLE）实时观察这类患者小肠黏膜在经受食物刺激之后的结构/功能变化。对食物刺激之后发生功能性改变的患者(CLEt)执行个性化排除饮食并随访观察是否有长期的缓解状况发生。
方法：在德国Kiel医院使用CLE检查了36名疑似食物耐受不良的IBS患者和10位无IBS症状的Barrett食管患者（对照组），稀释的食物抗原经内镜工作通道直接注入十二指肠黏膜上，在食物刺激之前和之后分别测量上皮破损、绒毛间隙、及上皮内淋巴细胞数量（IEL）。对CLEt患者行排除饮食，并随访一年；对照组继续之前的饮食。
结果：CLE显示36名患者中22名患者实时表现出对食物抗原的反应；36名患者中14名患者未发现对食物抗原的反应(CLE-)，对照组中的患者也没有观察到对食物抗原的反应。受试者中CLEt对比CLE-患者IEL基线明显升高，上皮渗漏/间隙，并发生绒毛间隙增宽。CLEt患者上皮渗漏和绒毛间隙与基线对比也显著增加（两者均p0.)。CLE和传统病理测量IEL数量的一致性为70.6%；两者并未相互关联(P1?4.89;r21?40.)。CLEt患者症状评分在进行四周排除饮食后提高超过50%，12个月后超过74%；CLE-患者的症状一如既往。
结论：根据CLE对疑似食物不耐受IBS患者的分析，接触候选食物抗原可导致小肠黏膜即刻出现上皮破损、绒毛间隙增宽及IEL数量增加。出现这些改变的患者对排除饮食疗法会产生反应。注册于clinicaltrials.gov(注册号：NCT).
ConfocalEndomicroscopyRevealsFood-AssociatedChangesintheIntestinalMucosaofPatientsWithIrritableBowelSyndrome
AnnetteFritscher-Ravens,1DetlefSchuppan,2,3,4MarkEllrichmann,1StefanSchoch,1ChristophR?cken,5JochenBrasch,6JohannesBethge,1MartinaB?ttner,7JuliusKlose,andPeterJ.Milla8
1UnitofExperimentalEndoscopy,DepartmentofInternalMedicineI,5DepartmentofPathology,6DepartmentofDermatology,74UniversityHospitalSchleswig-Holstein,Kiel,Germany;2InstituteofTranslationalImmunology,DepartmentofMedicineI,ResearchCenterforImmunology,UniversityofMainz,Mainz,Germany;4DivisionofGastroenterology,BethIsraelDeaconess76MedicalCenterandHarvardMedicalSchool,Boston,Massachusetts;7DepartmentofAnatomy,ChristianAlbrechtUniversity,77Kiel,Germany;8UCLInstituteofChildHealth,UniversityCollegeLondon,London,UnitedKingdom
BACKGROUNDAIMS:Weinvestigatedsuspectedfoodin-tolerancesinpatientswithirritablebowelsyndrome(IBS)usingconfocallaserendomicroscopy(CLE)forreal-timevisualizationofstructural/functionalchangesintheintesti-nalmucosaafterfoodchallenge.Patientswithfunctionalchangesafterfoodchallenge(CLEt)wereplacedonperson-alizedexclusiondietsandfollowedupforlong-termsymptomrelief.
METHODS:Thirty-sixIBSpatientswithsuspectedfoodintoleranceand10patientswithBarrett’sesophagus(con-trols)withoutIBSsymptomswereexaminedbyCLEatUni-versityHospital(Kiel,Germany).Dilutedfoodantigenswereadministereddirectlytotheduodenalmucosathroughtheworkingchanneloftheendoscope.Epithelialbreaks,inter-villousspaces,andthenumberofintraepitheliallymphocytes(IEL)weremeasuredbeforeandafterthefoodchallenge.CLEtpatientswereplacedonexclusiondiets,givensymptomscorequestionnaires,andfollowedupfor1year;controlsresumedtheirpreviousdiet.
RESULTS:CLEshowedareal-timeresponsetofoodantigensin22of36patients;nore-sponseswereobservedin14of36patients(CLE-)oranyofthecontrols.BaselineIELsweresignificantlyhigherinCLEtthanCLE-subjects(P1?4.);numbersincreasedsignificantlyafterfoodchallenge(P1?4.).Within5minutesofexposureofCLEtpatientstofoodantigens,IELsincreased,epithelialleaks/gapsformed,andintervillousspaceswidened.EpithelialleaksandintervillousspacesalsoincreasedsignificantlyinCLEtvsbaseline(bothP.).TheconcordanceofIELsmeasuredbyCLEandconventionalhistologywas70.6%;theydidnotcorrelate(P1?4.89;r21?40.).Symptomscoresimprovedmorethan50%inCLEtpatientsaftera4-weekexclusiondietandincreasedto74%at12months;symp-tomscontinuedinCLE-patients.CONCLUSIONS:BasedonCLEanalysisofIBSpatientswithasuspectedfoodintolerance,exposuretocandidatefoodantigenscausedimmediatebreaks,increasedintervillousspaces,andincreasedIELsintheintes-tinalmucosa.Thesechangesareassociatedwithpatientre-sponsestoexclusiondiets.Registeredatclinicaltrials.gov(registrationnumber:NCT).
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