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SmallIntes+nalBacterialOvergrowth:UpdatesandClinicalImplica0ons
Chris&neStubbe,ND,FABNO
LahnorPowell,ND,MPHMedicalEduca0onSpecialist-Atlanta
Chris0neStubbe,ND,FABNO
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SmallIntes+nalBacterialOvergrowth:UpdatesandClinicalImplica0ons
Chris&neStubbe,ND
• OverviewofSIBO• Learnwhentoconsidertes&ngforSIBO• Reviewthetestindetail• Discusstreatmentrecommenda&ons• Caseexamples• GIandothertestconsidera&ons
LearningObjec0ves
• “SmallIntes&nalBacterialOvergrowthisaheterogeneoussyndromecharacterizedbyanincreasednumberand/orabnormaltypeofbacteriainthesmallbowel.”
• “SIBOisacondi&oninwhichthesmallboweliscolonizedbyexcessivenumbersofaerobicandanaerobicmicrobesthatarenormallyfoundinthelargeintes&ne.”
• “Currentlyabacterialconcentra&onof>103c.f.u./mlisgenerallyconsideredsignificant.”
WhatisSmallIntes0nalBacterialOvergrowth?
SachdevAH,etal.Therapeu&cadvancesinchronicdisease.Sep2013;4(5):223-231.RezaieA,et.al.TheAmericanJournalofGastroenterology.2017;112:775-784.
BacterialConcentra0onsThroughouttheGITract
MowatA,etal.NatureReviewImmunology.2014;14(10):667-85.
• Gastricacid• Pancrea&candbiliarysecre&ons• Peristalsisandthemigra&ngmotorcomplex(MMC)–stasispromotesbacterialgrowth
• Ileocecalvalve–preventsrefluxofcolonicbacteriaintothesmallintes&ne
ThecompromiseofanyoftheseprocessescanleadtothedevelopmentofSIBO
WaystheBodyInnatelyPreventstheOvergrowthofBacteriaintheSmallIntes0ne
BuresJ,etal.WorldJournalofGastroenterology.2010;16(24):2978-90.HusebyeE.NeurogastroenterologyandMoAlity.1999;11(3):141-61.
MachadoWM,etal.ArquivosdeGastroenterologia.2008;45(3):212-18.PylerisE,etal.Diges&veDiseaseandScience.2012;57(5):1321-29.
WilliamsC.BestPracAceandResearch.ClinicalGastroenterology.2001;15(3):511-21.
WhentoConsiderSIBO?SignsandSymptomsAssociatedCondi&onsandRiskFactors
WhataretheCommonSignsandSymptomsofSIBO?
• Abdominalbloa&ng• Excessivegasorbelching• Abdominalcramps• Diarrhea• Cons&pa&on• Nausea• Heartburn
• Steatorrhea• Nutrientdeficiencies
– VitaminB12– Iron– Macronutrientmalabsorp&on– Fat-solublevitamins– RBCfolate
Condi0onswithaHighPrevalenceofOvergrowth
• Func&onalGIandmo&litydisorders(suchasIBS&gastroparesis)
• NeuromuscularDiseases(suchasrestlesslegsyndrome)
• InflammatoryBowelDisease(IBD) • Pancrea&cdisease• Celiacdisease
• Hypothyroidism• Liverdisease• Diabetes • Fibromyalgia• Rosacea • Parkinson’sdisease• Obesity • Plusmanyothercondi&ons
CostaMB,etal.ArquivosdeGastroenterologia.2012;49(4):279-83.Lauritano,et.al.JournalofClinicalEndocrinologyandMetabolism.2007;92(11):4180-84.
Mar&nsCP,etal.ArquivosdeGastroenterologia.2017;54(2):91-95.QueraPR,etal.RevistaMedicadeChile.2005;133(11):1361-70.
• IBS– 78%ofpa&entsposi&ve– 48%ofpa&entstreatedsuccessfullyforSIBOnolongermetRomecriteria
• FibromyalgiaandChronicFa&gueSyndrome– 42/42pa&entswithfibromyalgiahadanabnormallactulosebreathtestwithsignificantlygreaterhydrogenproduc&on;significantcorrela&onbetweendegreeofpainandpeakhydrogenlevel
– 77%ofCFSpa&entswerefoundtohaveSIBO
• Hypothyroidism– 54%ofpa&entswithhypothyroidismhaveSIBOcomparedwith5%ofcontrols– “Hypo-andhyperthyroidism,olenofautoimmuneorigin,arerespec&velyassociatedtosmallintes&nalbacterialovergrowthandtochangesinmicrobiotacomposi&on.”
PrevalenceofSIBOinCommonCondi0ons
LauritanoEC,et.al.JournalofClinicalEndocrinologyandMetabolism.2007;92(11):4180-84.PimentelM,et.al.AnnualsoftheRheumaAcDiseases.2004;63(4):450-52.
PimentelM,etal.AmericanJournalofGastroenterology.2000;95(12):3503-06.PimentelM,et.al.AmericanJournalofGastroenterology.2000;118(4):A414.
ViriliC,etal.Endocrine.2015;49(3):583-87.
• MechanicalStasis– Structural/Anatomic:Smallintes&nediver&cula,strictures,surgery– Mo&lityDisorders:Gastroparesis,Medica&ons(i.e.opioidanalgesics)
• IrritableBowelSyndrome• Hypothyroidism• MetabolicDisorders:Diabetes• ElderlyAge• OrganSystemDysfunc&on:Liver,kidney,pancrea&cdysfunc&on,Crohn’s,Celiac• Immunodeficiencystates• Hypochlorhydria• Medica&ons:Recurrentan&bio&csandgastricacidsuppressors• GIInfec&on
WhatareRiskFactorsfortheDevelopmentofSIBO?
DukowiczAC,etal.GastroenterologyandHepatology.2007;3(2):112-22.Mar&nsCP,etal.ArquivosdeGastroenterologia.2017;54(2):91-95.
• Anovergrowthofbacteriainthesmallintes&necancause:– Blun&ngofthevilli– Thinningofthemucosaandcrypts– Increasedintraepitheliallymphocytes– Microscopicinflammatorychanges
SIBOCanCauseHistopathologicChangeofSmallIntes0ne
HaboubiNY,LeeGS,MontgomeryRD.AgeAgeing.1991;20:29-32.BuresJ,et.al.WorldJournalofGastroenterology.2010;16(24):2978-2990.
Lappinga,P,et.al.ArchPatholLabMed.2010;134(2):264-70.
Tes0ngforSIBOGoldStandard:AspirateandCultureBreathTes&ng
Disadvantages• Invasiveprocedureasthesmallintes&nemustbeintubatedsothataspiratescanbecollected
• Culture-basedtechniquesdonotallowforgrowthofallorganisms,thusmayunderes&matethebacterialpopula&on
• Poten&alforcontamina&onofinstrumenta&onandinaccuratesamplingduetotechnicalproblems
• Endoscopycanonlyreachtheupperpor&onofthesmallintes&neandcolonoscopycanonlyreachthelower,thusthesubstan&almiddlesec&onofthesmallintes&neisnotaccessiblebythismethod
GoldStandard
DukowiczAC,etal.GastroenterologyandHepatology.2007;3(2):112-22.
Aspirate of small bowel fluid followed by culture and bacterial count
• “Unlikebreathtes&ng,smallbowelaspira&onisinvasive,&me-consumingandcostly.”
• “BreathTes&ngisauseful,inexpensive,simpleandsafediagnos&ctestintheevalua&onofcommongastroenterologyproblems.”
BreathTes0ngversusSmallBowelAspira0on
RezaieA,et.al.TheAmericanJournalofGastroenterology.2017;112:775-84.
BreathTes0ngforSIBO
• Baselinebreathmeasurement• Drinksubstrate(lactulose)• Lactulosetransitsthroughsmallintes&ne-ifbacteriaarepresent,H2(hydrogen)orCH4(methane)gasisproduced
• H2andCH4absorbedthroughintes&nesintobloodstream
• Gasescarriedtolungsthroughbloodstreamandexpired
• Breathcollectedat&medpoints
RanaSV,etal.WorldJournalofGastroenterology.2014;20(24):7587-601.
Tes0ngSubstancesforSIBOBreathTest
Lactulose • Cannotbedigestedorabsorbedbyhumans,thuspassesthroughen&relengthofsmallintes&ne
• Advantage:Candiagnosedistalovergrowthwhichisthoughttobemorecommon
• Notassensi&veasglucose
Glucose• Glucoseisabsorbedwithinfirstfewfeetofsmallintes&ne,thuscanonlydiagnoseproximalovergrowth
• Disadvantage:Cannotdiagnosedistalovergrowth
• Accuratediagnosisofproximalovergrowth
• Veryimportanttoreviewtheinstruc&onswiththepa&entastheyaredetailedandspecific
• Impropercollec&oncanleadtoambiguousresults• Keyinstruc&ons:
– 4weeksprior:Noan&bio&cs,colonoscopyorbariumenema– 7daysprior:Nolaxa&ves,stoolsoleners,stoolbulkingagentsorantacids– 24hoursprior:Dietlimitedtoafewfoodsandnoprobio&cs– 12hoursprior(fas&ngwithonlywater):Nonon-essen&almedica&ons/supplements,toothpaste,gum,candiesormouthwash
– 1hourpriorandduringtes&ng(fas&ngwithonlywater):Nosmoking,sleeping,vigorousexerciseortoothpaste
Collec0onPackInstruc0ons
• Collec&ontechniquewith&mingandbreathingintothetubemayneedtobereviewedwiththepa&ent– Breathenormally,inhaleandhold5seconds– Exhalenormallyintomouthpiece(donotblowhard)– Inserttubeandremovealer2seconds– Record&mesonlabelsandrequisi&onform
Collec0onPackInstruc0onsCon0nued…
Greatdemonstra&onvideoforpa&entstowatchcanbefoundontheSIBOpageonwww.gdx.net:
www.gdx.net/product/bacterial-overgrowth-of-the-small-intes&ne-sibo-test
TestInterpreta0on
2017NorthAmericanBreathTes0ngConsensusGuidelines• Standardiza&onwaslackingregardingindica&onsfortes&ng,testmethodologyandinterpreta&onofresults
• Whoformedtheconsensusgroup?• Consensuswasreachedon26statementsintheareasofindica&ons,prepara&on,performance,interpreta&onofresultsandknowledgegaps
RezaieA,et.al.TheAmericanJournalofGastroenterology.2017;112:775-84.
BreathTests:3-Hourversus2-Hour
3-HourSIBOBreathTest 2-HourSIBOBreathTest
TestComponents
• Graphofhydrogen(H2)andmethane(CH4)
• Chartofbreathgasesatthe&medpoints
• Carbondioxide(CO2)evalua&onforqualitycontrol
• Actualcollec&on&mes• Evalua&onforhydrogen• Evalua&onformethane
• AriseofH2of>20ppmoverbaselineinthefirst90minutesoftes&ngisposi&veforSIBO
• Genova’sEvalua&onforhydrogenbasedonconsensuspaper;thiscutpointisseenwidelythroughouttheliterature
Evalua0onforHydrogen(H2)
• SignificanceofelevatedbaselineH2levelsinpa&entsrepor&ngadherencetofas&nganddietaryguidelinesisnotknown– Inasymptoma&cpa&ent,someclinicalgroupswithexper&seinSIBOmanagementmayconsideranelevatedhydrogenbaselineaposi&vetest
• Approximately8to27%ofindividualsdonotproduceH2duetothepresenceofmethanogenicmicrobiotawhichconsumehydrogenmoleculestoproducemethanegas– LowH2findingsthroughall&mepointsinasymptoma&cpa&entmayreflectafalsenega&veresult– Clinicalaqen&onshouldbeshiledtoevalua&onofCH4
Evalua0onforHydrogen
• Theconsensusgroupandotherpapersrefertoanabsolutevalueof10orgreateratanypointduringthetestasa“methaneposi&ve”result– Results10+willbeoutlinedinredandflaggedwithan“H”
• Peer-reviewedliteraturesuggestsanassocia&onwithcertainclinicalcondi&onsandmethanogenovergrowthatlevelsaslowas3ppm,CH4valuesbetween3and9mayindicatetheneedforclinicalinterven&oninthesymptoma&cpa&ent– Results3-9willbeoutlinedinyellow
• EmergingliteraturesuggeststhatunlikeH2,anelevatedCH4levelatbaselineiscommon
Evalua0onforMethane(CH4)
• U&liza&onofbreathmethanelevelsforSIBOassessmentiscontroversiallargelyduetoalackofvalida&onrelatedtodiagnos&cspecificssuchas&mingandmagnitudeofincrease– TheriseofCH4duringbreathtes&ngappearstonotbeassharpasH2
• However,CH4measurementsareincreasinglyobtainedtoaddressotherclinicalques&onssuchas:– Cons&pa&on
• Methanegasitselfmayslowintes&naltransit,andpa&entswithCH4-predominantbacterialovergrowthhavebeenfoundtobefive&mesmorelikelytohavecons&pa&oncomparedtoindividualswithH2–predominantovergrowth
• Theseverityofcons&pa&onhasbeenfoundtodirectlycorrelatewiththeCH4level– IrritableBowelSyndrome(IBS)– Obesity
Evalua0onforMethane
CarbonDioxide(CO2)
CarbonDioxide(CO2)ismeasuredineverysample.CO2levelsexceedingacceptablelimitsindicateroomaircontamina&onlikelyatthe&meofsamplecollec&on.IfCO2levelsexceedacceptablelimits,
sampleintegrityisques&onableandresultsaredesignatedasnon-reportable(NR).
ActualCollec0onTimes
Onthereport
Ontherequisi0onform
ActualTime• Theactual&meofcollec&onofsamplesisprovidedtoenhanceclinicalinterpreta&on• Theactual&mesreportedareu&lizedtodeterminetheactualintervalforcomparisontotherecommendedinterval
ActualInterval• Theactualintervalcanbecomparedtotherecommendedcollec&oninterval.Iftherecommendedcollec&onintervalisnotfollowedcorrectly,interpreta&onshouldbemadewithinthecontextofthealteredcollec&onschedule.Generally,devia&onsofafewminuteswillnotsignificantlyaltertheinterpreta&on.
• Ifthe90-minuteintervalismissed,evalua&onforhydrogenmaybeaffected,sincethecriteriafordiagnosisofhydrogen-producingbacterialovergrowthisby90-minutes
ActualCollec0onTimes
Trea0ngSIBOTreattheovergrowthProvidenutri&onalsupportCorrecttheunderlyingcause
• Forthemajorityofpa&entsdiagnosedwithaposi&vebreathtest,SIBOwilllikelybeachronicandrelapsingcondi&on– Forexample,onestudyfoundthat44%ofpa&entstreatedsuccessfullywithan&bio&csrelapsewithin9months
• Goalsoftreatmentarethreefold:– Treattheovergrowth– Providenutri&onalsupport– Correcttheunderlyingcause
Trea0ngSIBO
DukowiczAC,etal.GastroenterologyandHepatology.2007;3(2):112-22.LauritanoEC,etal.TheAmericanJournalofGastroenterology.2008;103(8):2031-35.
• Rifaximin• RifaximinplusNeomycin(orMetronidazole)• Botanicals
– Berberine– Allicin(componentofgarlic)– Oreganooil– Neem– Others
Trea0ngSIBO–TreattheOvergrowth
ChedidV,etal.GlobalAdvancesinHealthandMedicine:ImprovingHealthcareOutcomesWorldwide.2014;3(3):16-24.
Trea0ngSIBO–ProvideNutri0onalSupport
• Nutri0onalconsequencesinclude:– Weightloss– Fatsolublevitamindeficiency– VitaminB12deficiency– Irondeficiency– Lowserumbileacids– LowRBCfolatelevels
• CommondietsprescribedforSIBO– SpecificCarbohydrateDiet(SCD)– LowFODMAPs– ElementalDiet
• Themigra&ngmotorcomplex(MMC)describesthewavesofelectromechanicalac&vitythatsweepthroughtheintes&nesinaregularcycle
• TheMMCisresponsibleformovingbacteriafromthesmallintes&netothelargeintes&ne,aswellasforinhibi&ngmigra&onofcolonicbacteriaintotheterminalileum
• Suppor&ngop&malfunc&onoftheMMCincludes:– Mealspacingevery4-5hourswithovernight12hourfast– Useofprokine&cagents
• Pharmaceu&calagentssuchaslow-doseerythromycin,Tegaserod,low-dosenaltrexone,andPrucalopride
• Naturalagentssuchasginger,herbalbiqersandthebotanicalproductIberogast
Trea0ngSIBO–AddresstheCause
ChaixA,etal.CellularMetabolism.2014;20(6):991-1005.VantrappenG,etal.TheJournalofClinicalInvesAgaAon.1977;59(6):1158-1166.
• Revisittheslideonriskfactorsandassociatedcondi&ons.Afewexamplesofaddressingthecausemayinclude:– Discon&nua&onofmedica&ons:Tobediscussedbetweenpa&entandclinician(acid-blockingmedica&ons,medsthatslowtransit-opioidanalgesics,etc.)
– TreatHypothyroidism• TreatmentwithLevothyroxineassociatedwithgreaterincidenceofSIBO• Whatiscausingthehypothyroidism?
– Hypochlorhydria• Biqers,BetaineHCl,etc.• Whatiscausingthehypochlorhydria?
– Somecausescannotbereversed(i.e.surgicalaltera&ons);ongoingmanagementmaybenecessary.
• Considervisceralmanipula&onforadhesions
Trea0ngSIBO–AddresstheCause
BrechmannT,etal.WorldJournalofGastroenterology.2017;23(5):842-852.
www.siboinfo.comisaninforma0vewebsitemaintainedbyDr.AllisonSiebecker,ND,andincludestreatmentconsidera0ons
• Inapa&enttreatedforSIBO,manyvariablesaffectthedecisionofwhentoretest—includingthepa&ent’sunderlyingcondi&onanditsseverity,lengthoftreatment,etc…
• TheNAConsensusGrouprecommendsthatan&bio&csshouldbeavoidedfor4weekspriortotes&ng—thisrecommenda&onusuallyappliestoini&altes&ngforSIBO
• However,thereareemergingclinicalrecommenda&onswhichsuggestretes&ngpa&entswithinafewdaysofanµbialcoursecomple&ontoensureefficacyofthetreatment.TheNorthAmericanConsensusgroupaswellasotherssuggestthat‘breathtestsmaybeperformedshortlyalercessa&onofan&bio&ctherapytoconfirmeradica&on’
Retes0ng
RezaieA,et.al.TheAmericanJournalofGastroenterology.2017;112:775-84.
CaseExamplesCaseExample#1Hydrogenposi&ve,mildmethaneposi&veCaseExample#2Methaneposi&veAddi&onalScenario
• 34yofemalewithbloa&ngandalterna&ngdiarrheawithcons&pa&on
• SymptomsongoingsinceshecaughtaGIbugwhiletravelinginCentralAmerica9monthsago;didnotexperiencethesesymptomspreviously
• Certainfoodsareproblema&candshefindsherselfea&ngmorepaleototrytocontrolsymptoms
• Pa&entisveryac&veandkeepsbusywithworkandtravel;theIBSsymptomshaveinterferedwithdailyliving
CaseExample#1
CaseExample#1
• Hydrogenposi&veresults• Methaneyellow–moderate• Collec&onschedulefollowedcorrectly
• Treatment:Sincethepa&entdidhaveamixedIBS-typepicturewithalterna&ngdiarrheaandcons&pa&on,theclinicianchosetotreatbothmethaneandhydrogen-producingbacteria– BotanicalregimenincludingCandibac&nARandBRplusAllimed(formethane)x6weeks– BeginlowFODMAPsdiet– Mealspacingevery4-5hours
• Followup:Aler2months,thepa&entsymptomshadimproved,sotherewasnofollowuptes&ng.Thepa&entcon&nuedwiththemealspacingandmodifiedFODMAPs– Thegoalisnotcon&nuousFODMAPs,sincefermentablecarbohydrateisimportanttothehealthofthecommensalbacteriaofthelargeintes&ne.Thegoalwouldbetointroducefermentablecarbohydrates/resistantstarchesover&me
CaseExample#1
• 66yomalewithbloa&ngandexcessivebelchingandflatulence• Severecons&pa&onforaslongashecanremember• Hasupto2bowelmovementsperweekthataredifficulttopass,heconsidersthispaqernnormalforhim
• Obese,hypertension,hypothyroid,diabe&c• Takesoxycodonedailyforabackinjury3yearsago• EatsastandardAmericandiet
CaseExample#2
CaseExample#2
• Methane-posi&vetest• Hydrogennormal• Collec&onschedulefollowedcorrectly
• Treatment:– Theclinicianchosetotreatmethane-producingorganismswithRifaximinplusNeomycinx14days
– Aprokine&cwasprescribed–Mo&lPro(combina&onofgingerand5HTP)indefinitelyun&lchroniccons&pa&onresolves
– Magnesiumwasprescribeddailytoassistwithregularity– LevothyroxineRxwasswitchedtoArmourThyroid– Recommendedincreasingwaterintakefrom1cupdailytoatleast1-2Ldaily– Whilefiberisimportantforcons&pa&on,itwasavoidedini&allytoaddressSIBO– Lowcarbohydratedietrecommended(fordiabetes,obesity,andSIBO)
CaseExample#2
• Thelong-termfocuswiththispa&entwouldbetoworkonhisoverallhealthcondi&onsandhabitsthatmaypredisposetoSIBO(diabetes,hypothyroid,StandardAmericanDiet,oxycodoneuse)– TherecurrenceofSIBOiscommonespeciallyifunderlyingcondi&onsarenotaddressed– Thispa&ent’slifestyleandhealthcondi&onsareinflamma&on-promo&ng,sotransi&oningtoan&-inflammatorydiet/lifestylemaytake&me,inordertocomeoffoxycodone
• AGIEffectsComprehensivestoolanalysiswasalsoorderedforthispa&ent– IfthereareotherGIabnormali&es,forexamplepancrea&cinsufficiency,thenpancrea&cenzymescanbegiventohelpwithdiges&on(pancrea&cinsufficiencyiscommonwithdiabetes)
CaseExample#2
• LowH2andCH4throughoutthetestcouldindicate:– Itisanega&vetestforSIBO;considerothertes&ngtoassesse&ologyofpa&entsymptoms– IfbothH2andCH4arelowall3hours,itmaysuggestthepresenceofH2S-producingbacteria
• TheH2S-producingbacteriaconsumetheHthatwouldotherwisehavegonetothebacteriathatmakeH2orCH4
• H2Ssmellslikeroqeneggs,soifthisiswhatthepa&entexperiences,thismaybethecase
– Thepa&entmaynothavefollowedcollec&onpackinstruc&onscorrectly• Thebreathdidn’tmakeitintothetube• Theymayhavejustcompletedan&bio&cs
– Instruc&onssaywait4weeksalerdiscon&nuingan&bio&cs– Somecliniciansmayadvisetheirpa&enttocollectimmediatelyalerfinishingan&bio&cstoensureefficacyoftreatment
Addi0onalScenario:“FlatlineTest”
© Genova Diagnostics
BanikGD,etal.JournalofBreathResearch.2016;10(2):026010.RezaieA,etal.TheAmericanJournalofGastroenterology.2017;112(5):775-84.
GITestConsidera0onsSIBOOthertests
• IBS• GIsymptoms• Bloa&ng• IntolerancetocarbohydratesorFODMAPs• Symptomsalerea&ng• Unexplainedabdominalsymptoms• Predisposingcondi&ons(seelist)
Itisimportanttodesignatesomeoneintheofficetogoovercollec+onpackageinstruc+onswitheachpa+enttoensureop+malresults
Review:WhentoOrderSIBOTes0ng
• GIEffectsiscomprehensiveandcaniden&fy:– Pancrea&cinsufficiency– Inflamma&on– Dysbiosis– Yeastovergrowth– Parasi&cinfec&on
• FoodAn&bodypanel• CeliacandGlutenSensi&vitypanel
OtherGITestConsidera0onsforSimilarSymptoms
GIEffectsprofilecannotdiagnoseSmallIntes0nalBacterialOvergrowth• Therearemarkersonthisprofilethatcanbesugges&veofSIBOintherightpa&entpopula&on:– Eleva&onsinProductsofProteinBreakdown– Eleva&onsinFecalFats– Unexpectedorextremeeleva&onsinTotalSCFAsandn-butyrate
GIEffects®ComprehensiveProfile
Nutri0onalInsufficiencies
• Bvitamins• Macronutrients• Fat-solublevitamins
TheNutrEvalassessesurineorganicacidsincludingmalabsorp0on
anddysbiosisbiomarkers
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TheviewsandopinionsexpressedhereinaresolelythoseofthepresenteranddonotnecessarilyrepresentthoseofGenovaDiagnos&cs.Thus,GenovaDiagnos&csdoesnotacceptliabilityforconsequencesofanyac&onstakenonthebasisoftheinforma&onprovided.
Chris&neStubbe,ND,FABNO
SmallIntes+nalBacterialOvergrowth:UpdatesandClinicalImplica0ons