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PresentedbytheCenterforMind-BodyMedicineandhostedbyKathieMadonnaSwift,MS,RDN,LDN.

LeakyGut:FactorFantasy?

Presentedby:SheilaDean,DSc,RDN,LDN,CCN,CDE,IFMCP

www.IFNAcademy.com

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Disclosure

• Co-founderoftheIntegrativeandFunctionalNutritionAcademy™• IFNA™ isanAccreditedProviderofCPEUsbytheCDR• IFNA™ offerstheIFNCP™,IntegrativeandFunctionalNutritionCertifiedPractitionerAdvancedPracticeCredential

LearningObjectives

• Describetherelationshipbetweenfoodexposure(i.e.gluten)andintestinalpermeability• Explaintherelationshipbetweenintestinalpermeabilityandinflammation• Discusstherelationshipbetweeninflammationandthespectrumofchronicdisease• Identifyamedicalnutritiontherapy(MNT)basedtreatmentplan

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Imagesource:EatingWell,July/August2016pg 27

“Leakygut”=Intestinal

permeability

TheBigPicture

Trigger intestinalpermeability- aka“leakygut”

Leakygut Immune/Inflammatoryresponse

Immune/inflammatoryresponse Chronicdisease

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Source:Bischoff,etalBMCGastroenterology,2014(seepreviousslide)8

LearningObjectives

• Describetherelationshipbetweenfoodexposure(i.e.gluten)andintestinalpermeability• Explaintherelationshipbetweenintestinalpermeabilityandinflammation• Discusstherelationshipbetweeninflammationandthespectrumofchronicdisease• Identifyamedicalnutritiontherapy(MNT)basedtreatmentplan

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Source:http://glutensensitivity.net/VojdaniDiagrams.htm#HG 10

Wenowrecognise thatthefunctionalstateofthetightjunction,onceconsideredastaticparameter,isinrealityincrediblydynamic.Epithelialtightjunctionsopenandcloseallthetimeinresponsetoavarietyofstimuli.These

includedietarystate,humoralorneuronalsignals,inflammatorymediators,mastcellproducts,andavarietyofcellularpathwaysthatcanbe

usurpedbymicrobialorviralpathogens.11

Zonulin istheonlyphysiologicmodulatorofintercellulartightjunctionsdescribedsofarthatisinvolvedinthetraffickingofmacromoleculesandthereforeintolerance/immuneresponsebalance.Whenthezonulin pathwayisderegulatedingeneticallysusceptibleindividuals,autoimmunedisorderscanoccur.

“TID”triggersofintestinalpermeability

ToxinsInfection

Dietaryproteins

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GlyphosateTestingnowavailable

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“TID”triggersofintestinalpermeability

ToxinsInfection

Dietaryproteins

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“ThisfindingsupportstheviewthatIPincreasesduringthecourseofprotozoaninfectionswhichcausedamagetotheintestinalwallwhilenon-pathogenicprotozoaninfectionshavenoeffectonIP.TheincreaseinIPinpatientswith B.hominis bringsforththeideathat B.hominis canbeapathogenicprotozoan.”

..thesestudiesshowforthefirsttimethatLPScausesanincreaseinintestinalpermeability..

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Whenthefinelytunedzonulin pathwayisderegulatedingeneticallysusceptibleindividuals,bothintestinalandextraintestinalautoimmune,inflammatory,andneoplasticdisorderscanoccur.

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“TID”triggersofintestinalpermeability

ToxinsInfection

Dietaryproteins

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Justthebasics:Whatisgluten?

• Glutenisamixtureofproteinsfoundinwheatandrelatedgrains,includingalltheirspeciesandhybrids.Itiscomposedoftwoprimarysubfractions:• Prolamines• Glutelins

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TheProlamine FractionofProteinsinGrains

GRAIN PROLAMINE %TOTALPROTEIN

Wheat Gliadin 69

Rye Secalinin 30-50

Oats Avenin 16

Barley Hordein 46-52

Millet Panicin 40

Corn Zien 55

Rice Orzenin 5

Sorgum Kafirin 52

Source:http://www.nutramed.com/celiac/gluten.htm 29

SpectrumofGlutenRelatedDisorders

Sapone A.etal.Spectrumofgluten-relateddisorders:consensusonnewnomenclatureandclassification.BMCMedicine.2012,10:13.30

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Howmanyknoworsuspectasensitivitytogluten?

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Eur J of Gastro & Hepatology 2014, Vol 26 No 1

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Thereisanemergingproblemencounteredinclinicalpracticeofpatientscomplainingofgluten-relatedsymptoms

despitetheabsenceofdiagnosticmarkersforCD,suchasnegativecoeliacserologyandnormalduodenalbiopsies.

Eur J of Gastro & Hepatology 2014, Vol 26 No 1

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Thesepatientsposeaclinicaldilemmatohealthcareprofessionalsandinthepasthavebeendescribedasbelongingtoa ‘noman’sland’duetothediagnostic

uncertainty.

Ok,soshouldIgoglutenfree?

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Source:ReillyN.TheGlutenFreeDiet:RecognizingFact,FictionandFad.JournalofPediatrics. 2016.DOI: http://dx.doi.org/10.1016/j.jpeds.2016.04.014

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British Journal of Nutrition (2010), 104, 773

ItappearsthataGFDinbothcoeliacandnon-coeliacsubjectscouldproducesimilar,potentiallyadversechangesinthemicrobiotasolelyonthebasisofa

markedreductioninintakeofnaturallyoccurringfructans whichhaveprebioticaction.

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Br J of Nutrition (2009), 102, 1154–1160

Therefore,theGFDledtoreductions inbeneficialgutbacteriapopulationsandreductionsintheabilityoffaecal samplestostimulatethehost’simmunity.

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British Journal of Nutrition (2010), 104, 773

Provisionofgluten-freebutprebiotic-richfoodsand/orasupplementoffructan-typeprebioticscouldavoidthissituationand,insodoing,provide

importantsupporttotheintestinalmicrobiotaaswellasimportantnutritionalguidanceforthecoeliacpatient.

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Alargenumberofhumaninterventionstudieshavebeenperformedthathavedemonstratedthatdietaryconsumptionofcertainfoodproductscanresultinstatisticallysignificantchangesinthecompositionofthegutmicrobiotainlinewiththeprebiotic

concept.Thustheprebioticeffectisnowawell-establishedscientificfact.

Asaresultoftheresearchactivitythatfollowedthepublicationoftheprebioticconcept15yearsago,ithasbecomeclearthatproductsthatcauseaselectivemodificationinthegutmicrobiota'scompositionand/oractivity(ies)andthusstrengthensnormobiosis couldeitherinducebeneficialphysiologicaleffectsinthecolonandalsoinextra-intestinal

compartmentsorcontributetowardsreducingtheriskofdysbiosis andassociatedintestinalandsystemicpathologies. 41

Theuseof probiotics seemstoreducetheinflammatoryresponseandrestoreanormalproportionofbeneficialbacteriainthegastrointestinaltract.

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Thegrainwithtwofaces

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“Conclusions:IncreasedintestinalpermeabilityaftergliadinexposureoccursinALLindividuals.”

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..wheatalsoprovidessubstantialamountsofanumberofcomponentswhichareessentialorbeneficialforhealth,notablyprotein,vitamins(notablyBvitamins),dietaryfiber,andphytochemicals..

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LearningObjectives

• Describetherelationshipbetweenfoodexposure(i.e.gluten)andintestinalpermeability• Explaintherelationshipbetweenintestinalpermeabilityandinflammation• Discusstherelationshipbetweeninflammationandthespectrumofchronicdisease• Identifyamedicalnutritiontherapy(MNT)basedtreatmentplan

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Theincreaseinintestinalpermeabilityismostlikelycausedbyinflammation-inducedparacellular permeability,ratherthan

ischemia-mediatedenterocytedamage.48

Specificgutbacteriaseemtoserveaslipopolysaccharide(LPS)sourcesandseveralreportsclaimaroleforincreasedintestinalpermeabilityinthe

genesisofmetabolicdisorders….InAsianIndianswhoareconsideredhighlyinsulinresistant,thecirculatoryLPSlevels,LPSactivity,andZO-1were

significantlyincreasedinpatientswithtype2diabetesandshowedpositivecorrelationwithinflammatorymarkersandpoorglycemic/lipidcontrol.

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Recentstudiesinvestigatingtheunderlyingmechanismsinvolvedindiseasedevelopmentindiabetespointtotheroleofthedysregulationoftheintestinalbarrier.Viaalterationsintheintestinalpermeability,

intestinalbarrierfunctionbecomescompromisedwherebyaccessofinfectiousagentsanddietaryantigenstomucosalimmuneelementsisfacilitated,whichmayeventuallyleadtoimmunereactionswithdamageto

pancreaticbetacellsandcanleadtoincreasedcytokineproductionwithconsequentinsulinresistance.

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Itisrecognizedthatachroniclow-gradeinflammationandanactivationoftheimmune

system areinvolvedinthepathogenesisofobesity-relatedinsulinresistanceandtype2diabetes.

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“Researchresultsseemtobeverypromisingandindicatethepossibilityofimprovedclinicaloutcomesinsomepatientswithschizophreniabymodifyingdiet,use

ofprobiotics,andtheimplementationofantibiotictherapyofspecifictreatmentgroups.”

LearningObjectives

• Describetherelationshipbetweenfoodexposure(i.e.gluten)andintestinalpermeability• Explaintherelationshipbetweenintestinalpermeabilityandinflammation• Discusstherelationshipbetweeninflammationandthespectrumofchronicdisease• Identifyamedicalnutritiontherapy(MNT)basedtreatmentplan

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1. Removea. Toxinsb. Infectionc. Dietarytriggers

2. Replacea. HCLb. Digestiveenzymes

3. Reinoculatea. probiotics

4. Repaira. Glutamine/SCFAsb. Fishoilsc. curcumin

HealingLeakyGutwiththe4RGIRestorationProtocol

Source:InstituteforFunctionalMedicine

Whattoconsidereliminating:• Gluten(r/oceliacdiseasefirst,ifpossible)• Dairy• Corn?Soy?Grains?animalprotein?• Refinedsugar• Infection• Toxins(alcohol,preservatives,smoking,stress)

Whattoconsideradding:• Betaine HCL,broadspectrumdigestiveenzymes• Probiotics/prebiotics/fermentedfoods• Glutamine(doselowandgoslow)/zinccarnosine• Methylatednutrients(B2,B6,folate,B12,CoQ10)• Omega-3fishoils• Fiberrichfoods/prebiotics• Antioxidant/phytochemicalrichfoods(i.e.freshfruitsandvegetables,seeds,nuts,legumes,etc.)

Onceyouhaveagoodhistory,testresultsetc.,youcanformulatetherestofyourNutritionCarePlan

Imagesource:www.IFNAcademy.com

KeyTakeaways

• Impairedintestinalpermeabilityisrealphenomenonthatispartofthe“3leggedstool”thatleadstoautoimmunity

• Triggerscanincludetoxins,infection,diet(TID)

• Impairedintestinalpermeabilitycanbehealedusingthe4Rprotocol

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Presentersfromlefttoright:Alessio Fasano,MD;SheilaDean,DSc,RDN,AndreaScaramuzza,MD76th ADAAnnualSymposium- June12,2016

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