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MiroslavFö
rstl,InstituteofClinicalMicrobiology,CharlesUniversityinPraha,FacultyofMedicineatHradecKralove,UniversityTeachingHospital,Sokolska581,50005HradecKralove,CzechRepublic
JaroslavKvetina,InstituteofExperimentalBiopharmaceutics,JointResearchCentreofCzechAcademyofSciencesandPRO.MED.CSPrahaa.s.,Heyrovskeho1207,50003HradecKralove,CzechRepublic
ViktorVorisek,InstituteofClinicalBiochemistryandDiagnostics,CharlesUniversityinPraha,FacultyofMedicineatHradecKralove,UniversityTeachingHospital,Sokolska581,50005HradecKralove,CzechRepublic
Authorcontributions:
BuresJ,CyranyJ,KohoutovaD,Fö
rstlM,RejchrtS,KvetinaJ,VorisekVandKopacovaMcontributedequallytothiswork.
SupportedbyTheResearchProjectMZO00179906fromtheMinistryofHealth,CzechRepublic,andbyResearchGrantGACR305/08/0535,CzechRepublic
Correspondenceto:
JanBures,Professor,MD,PhD,2ndDepartmentofMedicine,CharlesUniversityinPraha,FacultyofMedicineatHradecKralove,UniversityTeachingHospital,Sokolska581,50005HradecKralove,
CzechRepublic.bures@lfhk.cuni.cz
Telephone:
+420-495-834240Fax:
+420-495-834785
Abstract
Humanintestinalmicrobiotacreateacomplexpolymicrobialecology.Thisischaracterisedbyitshighpopulationdensity,widediversityandcomplexityofinteraction.Anydysbalanceofthiscomplexintestinalmicrobiome,bothqualitativeandquantitative,mighthaveserioushealthconsequenceforamacro-organism,includingsmallintestinalbacterialovergrowthsyndrome(SIBO).SIBOisdefinedasanincreaseinthenumberand/oralterationinthetypeofbacteriaintheuppergastrointestinaltract.Thereareseveralendogenousdefencemechanismsforpreventingbacterialovergrowth:
gastricacidsecretion,intestinalmotility,intactileo-caecalvalve,immunoglobulinswithinintestinalsecretionandbacteriostaticpropertiesofpancreaticandbiliarysecretion.AetiologyofSIBOisusuallycomplex,associatedwithdisordersofprotectiveantibacterialmechanisms(e.g.achlorhydria,pancreaticexocrineinsufficiency,immunodeficiencysyndromes),anatomicalabnormalities(e.g.smallintestinalobstruction,diverticula,fistulae,surgicalblindloop,previousileo-caecalresections)and/ormotilitydisorders(e.g.scleroderma,autonomicneuropathyindiabetesmellitus,post-radiationenteropathy,smallintestinalpseudo-obstruction).Insomepatientsmorethanonefactormaybeinvolved.SymptomsrelatedtoSIBOarebloating,diarrhoea,malabsorption,weightlossandmalnutrition.ThegoldstandardfordiagnosingSIBOisstillmicrobialinvestigationofjejunalaspirates.Non-invasivehydrogenandmethanebreathtestsaremostcommonlyusedforthediagnosisofSIBOusingglucoseorlactulose.TherapyforSIBOmustbecomplex,addressingallcauses,symptomsandcomplications,andfullyindividualised.Itshouldincludetreatmentoftheunderlyingdisease,nutritionalsupportandcyclicalgastro-intestinalselectiveantibiotics.Prognosisisusuallyserious,determinedmostlybytheunderlyingdiseasethatledtoSIBO.
©
2010Baishideng.Allrightsreserved.
Keywords:
Bacterialovergrowth;
Breathtest;
Hydrogen;
Methane;
Smallintestine
Peerreviewers:
AntonioGasbarrini,MD,Professor,DepartmentofInternalMedicine,GemelliHospital,CatholicUniversityofRome,LargoA.Gemelli8,00168Rome,Italy;
AnthonyPMoran,BSc,PhD,DSc,FRSC,MRIA,Professor,DepartmentofMicrobiology,NationalUniversityofIrelandGalway,UniversityRoad,Galway,Ireland
BuresJ,CyranyJ,KohoutovaD,Fö
rstlM,RejchrtS,KvetinaJ,VorisekV,KopacovaM.Smallintestinalbacterialovergrowthsyndrome.WorldJGastroenterol2010;
16(24):
2978-2990Availablefrom:
URL:
DOI:
http:
//dx.doi.org/10.3748/wjg.v16.i24.2978
INTRODUCTION
Humanintestinalmicrobiotacreateacomplexpolymicrobialecology.Thisischaracterisedbyitshighpopulationdensity,widediversityandcomplexityofinteraction.Theduodenumandproximaljejunumnormallycontainsmallnumbersofbacteria,usuallylactobacilliandenterococci,gram-positiveaerobesorfacultativeanaerobes(<
104organismspermL).Coliformsmaybetransientlypresent(<
103bacteriapermL)andanaerobicBacteroidesarenotfoundinthejejunuminhealthypeople.Uptoonethirdofjejunalaspiratesmightbesterileinhealthyvolunteers.Thedistalileumisatransitionzonebetweensparsepopulationsofaerobicbacteriaoftheproximalsmallintestineandverydensepopulationsofanaerobicmicro-organismsinthelargebowel[1-3].Theepithelialsurfaceofthesmallintestineinahealthyhumanisnotcolonised.Occasionalgroupsofbacteriacanbefoundinlowconcentrationswithinthelumen.Bacteriadonotformclustersandspatialstructures,andtheluminalcontentsareseparatedfromthemucosabyamucuslayer[4].
Anydysbalanceofthiscomplexintestinalmicrobiome,bothqualitativeandquantitative,mighthaveserioushealthconsequencesforamacro-organism,includingsmallintestinalbacterialovergrowthsyndrome(SIBO).
definition
SIBOisaveryheterogeneoussyndromecharacterisedbyanincreasednumberand/orabnormaltypeofbacteriainthesmallbowel.MostauthorsconsiderdiagnosticofSIBOtobethefindingof≥105bacteria[i.e.colony-formingunits(CFU)]permLofproximaljejunalaspiration.Thenormalvalueis≤104CFU/mL[3,5-7].
prevalence
TheoverallprevalenceofSIBOinthegeneralpublicisunknown.Ingeneral,SIBOissubstantiallyunderdiagnosed.Thereareseveralreasonsforthisfact.SomepatientsmaynotseekhealthcareorSIBOmaynotbeproperlydiagnosedbymedicalinvestigations.SIBOmightbeasymptomaticorwithnon-specificsymptomsonly,andlastbutnotleast,allsymptomsmightbeincorrectlyascribedtotheunderlyingdisease(leadingtoSIBO).Ofcourse,diagnosticyieldalsodependsonthemethodsusedforinvestigation.Accordingtodifferentstudieswiththeinvestigationofsmallsetsofclinicallyhealthypeopleasacontrol,findingsconsistentwithSIBOwerefoundin2.5%to22%[8-17].
Inparticulardiseasesanddisorders,literaturedataonprevalencediffersubstantially.Forinstance,theprevalenceofSIBOinpatientsfulfillingdiagnosticcriteriaforirritablebowelsyndromewas30%-85%[9-11,16,18,19].TheprevalenceofSIBOincoeliacdiseasenon-respondingtoagluten-freedietwasupto50%[20].Inlivercirrhosis,SIBOwasdiagnosedinmorethan50%ofcases[21,22].Inasmallgroupofelderlypeople(70to94yearsold)withlactosemalabsorption,SIBOwasdocumentedin90%[23].AninterestingstudywasperformedonasymptomaticmorbidlyobesesubjectsandSIBOwasfoundin17%(comparedto2.5%innon-obesepersons)[15].
aetiology
Thereareseveralendogenousdefencemechanismsforpreventingbacterialovergrowth:
gastricacidsecretion,intestinalmotility,intactileo-caecalvalve,immunoglobulinswithinintestinalsecretionandbacteriostaticpropertiesofpancreaticandbiliarysecretion[24].
TheaetiologyofSIBOisusuallycomplex,associatedwithdisordersofprotectiveantibacterialmechanisms(e.g.achlorhydria,pancreaticexocrineinsufficiency,immunodeficiencysyndromes),anatomicalabnormalities(e.g.smallintestinalobstruction,diverticula,fistulae,surgicalblindloop,previousileo-caecalresections)and/ormotilitydisorders(e.g.scleroderma,autonomicneuropathyindiabetesmellitus,post-radiationenteropathy,smallintestinalpseudo-obstruction).Insomepatientsmorethanonefactormaybeinvolved.“Aetiological”and“predisposing”factorscannotbeseparatedinsomepatients.SIBOmayoccurinelderlypeoplewithoutanyevidentunderlyingsmallintestinalpathology.
Insomecases,aviciouscirclearises:
anunderlyingdiseaseiscomplicatedbySIBOandthenSIBOdirectly(asamorphologicalimpact)orvicariously(bymalabsorptionornutrientdeficiency)causesfurtherdeteriorationoftheunderlyingdisease.
OutofalldiseasesanddisordersassociatedwithSIBO(listedbelowindetail),90%ofcasescomprisesmallintestinalmotilitydisorders(ofvariousaetiology)andchronicpancreatitis[2].
Achlorhydria
Achlorhydria(duetochronicatrophicgastritis)andlong-termadministrationofprotonpumpinhibitorsmaycausebacterialovergrowthinthestomachandduodenum.Protonpumpinhibitorsnotonlyincreaseduodenalbacterialcolonisationbutalsoaccelerateintestinaltransit[24].
Exocrinepancreaticinsufficiency
ChronicpancreatitisiscomplicatedbySIBOin30%-40%ofcases[7,25].Multiplefactorscanbeinvolved:
exocrinepancreaticinsufficiency(withabsenceofanti-bacterialeffectofproteolyticenzymes),abnormalchymeinthesmallintestinallumen,motilitydisorders,administrationofpainkillersandongoingalcoholconsumptioninsomeofpatients.CysticfibrosisisalsoassociatedwithincreasedriskofSIBO.Fridgeetal[26]diagnosedSIBOin14/25(56%)patientswithcysticfibrosis.SIBOmaybeacausativefactorofdiarrhoeainadvancedpancreaticcancer[27]apartfrompancreaticexocrineinsufficiency,chemotherapyorprevioussurgery.
Immunodeficiencysyndromes
Variousimmunodeficiencysyndromes,suchasIgAdeficiency,commonvariableimmunodeficiency,AIDSandothers,arecomplicatedbymiscellaneousinfect