* your gut is killing you 2.10 gut is... · fasting & the gut fasting is a “way of not...

“Dr. Al” Danenberg Periodontist

Certified Functional Medicine Practitioner ADAPT Trained Health Professional

Certified Primal Health Coach https://drdanenberg.com/

YourGutisKillingYouIntroductionIproposeauniquestartingpointforchronicdiseasetoday.Aswiththecenterofawheel,differentpaths(likethespokesofawheel)spreadoutfromthiscentralpointprogressingthroughoutthebody.Thiscentralpointisthegut.Thespokesrepresentvariousformsofsystemicdisseminationleadingtoorgansystems.ThemechanismofdisseminationisbasedonsomecompellingmedicalresearchinvolvingtheGastrointestinalMucosalBorder(GIMB),whichisthegatewaytothesystemiccirculationthatcanbecompromised.1Theendresult,dependingontheindividual’sweaknessesorgeneticpredispositions,isthemanifestationofvariouschronicdiseases.Wellbeforeamedicalpractitionermightdiagnoseanyofthesechronicdiseases,viciouscyclesalreadymayhavebeeninplacetocomplicateitstreatment.

Thegenesisofmytheorybeginswithchangesinthegut.Changesinclude(1)anincreaseofunhealthymicrobesresultingindysbiosisinthegutand(2)changesinthepermeabilityofthegutliningresultinginleakageoftoxicsubstancesintothebloodsystem.2,3,4,5Ifthesechangesweretobecomepersistentandchronic,theycouldbecomepathogenic.6Then,asequalaeofcascadingeventscouldanddooccur.Inturn,thesechangescouldsetoffmanydifferingpathstochronicdisease.Fundamentally,yourgutmightbekillingyou.

FirstThingsFirstOurprimalancestorsrarelydevelopedchronicdisease.7Skeletalremainsofourdistantrelativessuggestthatdegenerativediseaseswerenotprevalentastheyaretoday.Infact,thefewprimalsocietiesinexistencetodayinremoteareasoftheworldrarelydevelopdegenerativechronicdiseases.8

Recenthumanstudieshaveshownthatdietandlifestylearedeterminantsofmetabolicsyndrome.9Medicalresearchhasshownthatmetabolicsyndromeisaprecursortomanychronicdiseases.Metabolicsyndromeisthenameforagroupofriskfactors,whichinclude:

1 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3384703/ 2 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5433529/pdf/BCJ-2016-0510C.pdf 3 http://www.altmedrev.com/publications/9/2/180.pdf 4 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4555153/ 5 http://dmd.aspetjournals.org/content/dmd/43/10/1557.full.pdf 6 https://www.ncbi.nlm.nih.gov/pubmed/29098118 7 http://ajcn.nutrition.org/content/81/2/341.long 8 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3402009/ 9 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4588744/

• Largewaistline

• Hightriglyceridelevel

• LowHDL-Cholesterollevel

• Highbloodpressure

• Elevatedbloodsugar

• Insulinresistance

Inaddition,publishedpapersdemonstratethatwhenhumansconsumenutrient-densefoods,avoidprocessedfoods,obtainrestorativesleep,exerciseefficiently,andmanagestressesofalltypes,thenalltherisksofmetabolicsyndromedecreasesignificantly.Dentalhealthaswellimprovessignificantly.10,11,12

Today,chronicdiseasesconsistofsuchconditionsasheartdisease,stroke,cancer,diabetes,obesity,andarthritistonameafew.Toothdecayandgumdiseasealsoarechronicdiseases.Chronicdiseaseshavemultiplecauses.AccordingtotheU.S.NationalCenterforHealthStatistics,chronicdiseaselasts3monthsormoreandgenerallycannotbepreventedbyvaccinesorcuredbymedication.Theyjustdon’tdisappearontheirown.TheCentersforDiseaseControlandPreventionstatedthat60%ofAmericanslivewithatleastonechronicdisease,andchronicdiseasesareresponsiblefor70%ofdeathseachyearintheUnitedStates.13Poorlifestyleandpooreatingchoicescausedamageinthegutovertimeleadingtochronicdisease.Thesepoorchoicescausechronicsystemicinflammation,andthedamageiscumulative.Chronicdiseasesleadtoadecreaseinqualityoflifeandadecreaseinlongevity.LifeexpectancyhasdecreasedintheUnitedStatesafter2014despitethefactthattheUSspendsfarmoreonhealthcarethananyothercountryintheworld.14Apparentlytherearemanycausesforthis,includingtheopioidepidemic,distracteddrivingduetocellphones,andanincreaseinsuicides.Butoneoftheprimarydriversisadramaticincreaseinoverweightandobesity.AccordingtotheCentersforDiseaseControlandPrevention,72%ofAmericansarenowoverweight,and40%areobese.15AsIhavediscussed,ourprimalancestorshardlyeverhad,andtoday’sprimitivesocietieshardlyeverhave,chronicdiseases.

10 https://www.ncbi.nlm.nih.gov/pubmed/19405829 11 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4962497/pdf/12903_2016_Article_257.pdf 12 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4856634/ 13 https://www.cdc.gov/chronicdisease/center/index.htm 14 https://www.ncbi.nlm.nih.gov/pubmed/?term=Life+Expectancy+and+Mortality+Rates+in+the+United+States%2C+1959-2017 15 https://www.cdc.gov/nchs/data/hus/2018/021.pdf

OurDiet&theGutOurdiet(thefoodsweeatandthefoodsweavoideating)hasamajorimpactonourqualityoflife,health,andlongevity.16Thefoodweeatdirectlyaffectsthegutmicrobiome.Inthis2014studypublishedinNature17,researchersshowedthattheshort-termconsumptionofdietscomposedentirelyofanimalorplantproductsrapidlyaltersthegutmicrobiome.Theinvestigatorsprovedthatthegardenofbacteriainthegutcanrapidlyrespondtoanaltereddiet,facilitatingthediversityofhumandietarylifestyles.

Humanshaveastomach,smallintestine,andlargeintestinethatarebetterdesignedtodigestanimalfoodsratherthanplantfoods.Humansareomnivorous,butoursmallintestinesarelargerthanthatofotherprimates,andthecolonissmaller.Otherprimates’largecolonisidealforhandlingplantsfoods.Inaddition,primatesotherthanhumanshaveacecumthathelpsthemfermentplantfoodsintoenergy.Humansdon’thaveacecumlargeenoughtodothis.Finally,thelarger-sizedhumansmallintestineisbetterdesignedthanthesmaller-sizedsmallintestinesofotherprimatestodigestanimalproteins,fish,eggs,andsomecookedplants.So,humans’digestivetractseemstofunctionbetteronanimal-basedfoodsratherthanplant-basedfoods.Asamatteroffact,researchersdeterminedfromfossilremainsthatNeanderthalManwasmostlycarnivorous.18AndnewevidencehasbeenuncoveredthathomosapiensinMoroccopredominatelyatemeatonaregularbasis.19

Thehumanbodyhasabout30trillionhumancells,butthegutmicrobiomeiscomposedofapproximately38trillionbacteria20,whichincludesover2,100differentspeciesofknownbacteriaandmorethan3milliongenes.21Thisgardenofmicrobesisinvolvedinseveralbiologicalfunctionssuchascarbohydratedigestion,reductionofharmfulmicrobes(bycompetitiveexclusion),vitaminsynthesis,immunesystemactivity,anddrugmetabolism.22,23Thecellsofourbodyandthegutmicrobiometalkbackandforth.Thiscrosstalkallowsforhomeostasisbetweenthebacteriaandthehost.24Whenthereisanimbalanceofmicrobesinthegut,itiscalled“dysbiosis”.Inahealthygut,BacteroidetesandFirmicutesarethedominantbacterialphylamakingupapproximately90%ofthetotalbacterialcommunity.Theremaining10%aremadeupofProteobacteria,Verrucomicrobia,andActinobacteria.25Dysbiosismanifestsbecauseofoneormoreofthefollowingcategories:(1)reductioninbeneficialmicroorganisms,(2)overgrowthofharmfulmicroorganisms,and(3)reduced

16 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524347/ 17 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3957428/ 18 https://www.academia.edu/463164/Isotopic_biogeochemistry_13C_15N_of_fossil_vertebrate_collagen_application_to_the_study_of_a_past_food_web_including_Neandertal_man 19 https://www.ncbi.nlm.nih.gov/pubmed/28593953 20 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4991899/ 21 https://www.ncbi.nlm.nih.gov/pubmed/26311042 22 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4528021/ 23 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5964925/ 24 https://www.ncbi.nlm.nih.gov/pubmed/29630505 25 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143175/

diversityofmicroorganisms26,allofwhichpotentiateanincreaseininflammationandGIMBinfections.

Short-ChainFattyAcidsWhenfunctioninginahealthymanner,thegutmicrobiomeproducesvariousshort-chainfattyacids(SCFAs).27TheproductionofSCFAsinsufficientquantitiesisthedistinctivefeatureofhealthydiets.AmajorsourceofSCFAsinthegutistheanaerobicfermentationofpolysaccharidesthatareindigestiblebythehost.Thesepolysaccharidesarethefiberinourdietwhentheyareavailableinourdiet.TheSCFAsthatareproducedareacetate,propionate,butyrate,andlactate.However,recentresearchhasshownthatourgutbacteriaalsocancreateSCFAsfromaminoacids.28So,itispossiblethatanabundanceofaminoacidscouldreplacetherequirementforahighfiberdietorwhenfiberislackinginthediet.Butyrateisthemostimportantenergysourceforhealthycolonocytes,whichbecomeimpairedinpathologicalconditionsofcolitisandcoloncancer.Butyratehasbeenshowntoinhibitproliferationandpromotedifferentiationandapoptosisindifferentcancers.29Butyratealsoinhibitspro-inflammatorynuclearfactor-κBsignalingandtumorigenesis.Acetateisusedasacholesterolorfattyacidprecursor,whereaspropionateisgluconeogenicintheliverandthegut.Acetatealsomayneutralizelipogenesisfromacetateorglucoseintheliver.

Fasting&theGutFastingisa“wayofnoteating”.Itistherestrictionoffoodsothatthebodycan“rest”.Fastingincludesintermittentfasting,24-hourfasting,andmulti-dayfasting.Intermittentfastingiseatingduringawindowof8hoursorlessandfastingforabout16hoursormoreoverthecourseofa24-hourday.Forexample,apersoncouldstopeatingallfoodat8PMintheeveningandnoteatfooduntilnoonthenextday.Inthisexample,thewindowofeatingisfromnoonto8PM.Fastinghasbeenassociatedwithnumeroushealthbenefits.30Oneoftheprimarymechanismsthroughwhichfastinginducesmetabolicimprovementsisthepositiveeffectsonthegutmicrobiome.31RestrictingfoodalsodecreasesthegrowthofpathogenicProteobacteriawhileincreasingbeneficialAkkermansiamuciniphilalevels32,agram-

26 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4838534/ 27 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6244749/ 28 https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-019-0704-8 29 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3070119/ 30 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4250148/ 31 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5668683/ 32 https://www.ncbi.nlm.nih.gov/pubmed/29620942

negativeanaerobethatusesmucinasitssourceofcarbonandnitrogen.Thisresultsinmucindegradation,whichpromotesanti-inflammatoryeffects.33Anotherbenefitoffastingisrelatedtocancertreatment.Fastingpromotesapoptosisincoloncancermodelsandinducesananti-Warburgeffect34,whichischaracterizedbyincreasedoxygenconsumptionbutfailuretogenerateATP,resultinginoxidativedamageandapoptosis.35

TheWarburgeffect:Allcancercells,regardlessoftissueorigin,usefermentationenergyforgrowth,whilestoringenergyinATPmolecules.Cancercellsfermentlacticacidfromglucose(acarbohydrate)inthecytoplasmandfermentsuccinicacidfromglutamine(anaminoacid)inthemitochondria.EvenwhentumorcellsappeartobemakingATPandtakinginoxygen(whichwouldbenormalrespiration),theirmitochondriaareabnormal.Therefore,mitochondrialdysfunctionisattherootofmostcancers.Bottomlineisthatthetrueoriginofcancerisdamagetotherespiratoryfunctionofyourmitochondria,triggeringcompensatoryfermentation,whichisrunbyoncogenes(genesthathavethepotentialtocausecancer).Oncogenesfacilitatetheentryofglucoseandglutamineintothecelltoreplaceoxidativephosphorylation.36

Ananti-Warburgeffectisthemetabolicshiftfromfermentationtooxidativephosphorylation.Restoringtheoxidativemetabolismthroughmitochondrialbiogenesisprovidesatherapeuticstrategyforcancer.

UnhealthyDiets&theGut37TheStandardAmericanDiet(alsoknownastheWesterndiet)ishighlyassociatedwithobesityandrelatedmetabolicdiseases.TheWesterndietpromotesinflammation,whichiscausedbyunhealthychangesinthegutmicrobiome.Thisdietisloadedwithover-processedfoodsincludinggrainproducts,sugars,vegetableandseedoils,fatsfromanimalsfedgrainproductsandraisedwiththeuseofantibioticsandhormones;theuseofagrichemicalstoensuremaximumharvestpotential;andpreservativesandotherchemicalresiduesincludedintheprocessingofpackagedfoods–alltomaximizecommercialviability.

HealthyDiets&theGutImportantcaveat:EatOrganicTounderstandhealthyfood,youmustunderstand“organic”.The“OrganicSeal”isacertification,whichonlycanbeawardedbytheU.S.DepartmentofAgriculture(USDA)tofoodsandfoodproducts.

33 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4365749/ 34 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4783224/ 35 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4494906/ 36 https://nutritionandmetabolism.biomedcentral.com/articles/10.1186/1743-7075-7-7 37 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5872783/

Foraproducttobecertifiedorganic,it’srequiredtomeetthesestrictstandards:

• Organiccropscannotbegrownwithsyntheticfertilizers,syntheticpesticidesorsewagesludge.

• Organiccropscannotbegeneticallyengineeredorirradiated.

• Animalsmusteatonlyorganicallygrownfeed(withoutanimalbyproducts)andcan’tbetreatedwithsynthetichormonesorantibiotics.

• Animalsmusthaveaccesstotheoutdoors,andruminants(hoofedanimals,includingcows)musthaveaccesstopasture.

• Animalscannotbecloned

Inthepracticalworld,somelocalfarmsareunabletomeetthefinancialexpensestogaintheOrganicSeal.However,theirproductsmaybegrownandraisedaccordingtothestandardsIoutlinedabove.Ifyoucanascertainthatyourlocalfarmeriscompliantwiththerequirementstobe“organic”buthasnotbeenabletoaffordthecoststoreceivethe“OrganicSeal”,thatwouldbeacceptable.Youshouldeat“organic”foodswheneverpossible.Also,theplantsthatanimalsconsumefortheirnormal,unadulteratedsupplyoffoodshouldbeorganic.Animalsshouldbeeither100%wild-caughtor100%pasture-raisedasmuchaspossible.Theyshouldnotbeconventionallyraisedandconfinedincagesorfeedinglotswithinorganicandunnaturalfoodsonwhichtofeed.Healthyanimalmeatandorganssupportahealthygutmicrobiome,whichcanproducemetabolitesthatmaypreventcancer.38Herearesomecompellingreasonstoeat“Organic”:

• Plantsmanufacturephytonutrientsinsidetheircells.Thesephytonutrientsareliketheimmunecellsinourbody,andtherearemorethan25,000differentphytonutrientsfoundinplants39,withmorebeingdiscoveredallthetime.Thesenutrientshelptheplantstofightinfectionsandmaintaintheirhealth.Manyofthesephytonutrientsmaybenefitus.Itisreportedthattheymayhavehealth-promotingpropertiesincludingantioxidant,anti-inflammatory,andotherbiologicalactivities.Thedeepcolorsinplantsrepresenttheintensityofthephytonutrientsavailabletous.However,someofthesephytonutrientsmaybeharmfulforsomeofus.

38 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4549221/ 39 http://www.webmd.com/diet/phytonutrients-faq

• Ifplantsareexposedtomanyinsultsfromtheirenvironment,theydevelopmoreintensephytonutrientsforself-protection.Ifplantsarenotexposedtotheseinsults,theydevelopfewerphytonutrients.Whenplantsaresprayedwithinsecticidesandotherchemicalstokilloffpredatorsandmicrobes,theseplantsnotonlyhaveachemicalresiduethatisnothealthyforhumans,butalsoproducefewerphytonutrients.Eatingorganicnotonlyreducesourtoxicexposurefromthesprayedchemicalsbutalsoincreasesthequantityandqualityofthephytonutrients.Locallygrownisbetterthangrownthousandsofmilesawaybecauselocallygrownisfresher.Locallygrownproduce,forexample,isalsopickedclosesttooptimalripenesswhenbeneficialnutrientcontentsareattheirhighestandsomeplantchemicalsthatmaybetoxictohumans(i.e.lectinsandphytoestrogens,etc.)areattheirlowest.Thisisalsothetimewhenflavorisatitsbest.Protectiveplantchemicalssuchaslectinsandphytoestrogens(whicharepotentiallydamagingtothegut)actaspestrepellentstoprotecttheplantfrompestsduringitsdevelopmenttowardsmaturity,maximumnutritionalvalue,andfullripeness.Forthepurposesofnotspoilingoverlongshippingdistances,plantsgrownmanymilesawayarepickedwellbeforetheirpeakripeness;havereducednutrientcontentsandbenefits;andhavehigherlevelsofprotectiveplantchemicals,whichcontributetoadversehealthconsequences,includingdamagetotheGIMB.Imustnotethatsomeofthesephytonutrients,whichhavebeentoutedtobehealthy,maybeharmfulforsomeofus.

• Plantsgrowandthrivefromtheinfluenceofrain,thenutrientsandmicrobesinthesoil,andthesun.Whenplantshavebeensprayedwithvariouschemicals,thesechemicalscanpenetratethesoil.Theycandestroynecessarysoilmicrobesthatarerequiredtoproducehealthynutrientsinthesoil.Therefore,non-organicplantscouldbedeficientinnecessarynutrientsbecauseofcontaminatedsoils.

Several“diets”havebeenshowntobenefitthegutmicrobiome.TheyincludetheMediterraneanDiet,Low-CarbohydrateDiet,KetogenicDiet,thePaleolithicDiet,andmostrecentlytheCarnivoreDiet.

Mediterraneandiet:Thistypeofdiet40consistsofeating:(a)highlevelsofvegetables,fruits,cereals(mostlywholegrains),nuts,andlegumes;(b)lowlevelsofsaturatedfat,sweets,andmeat;(c)highlevelsofunsaturatedfat(mainlyoliveoil);(d)medium-highlevelsoffish;(e)moderatelevelsofwine;and(f)medium-lowlevelsofdairyproducts(mainlyyogurtandcheese).EatingthiswayisassociatedwithreducedinflammationandincreasedlevelsofSCFAsproduction.Low-carbohydratediet:Restrictingprocessedcarbohydratesandsugarsavoidshyperglycemiaandhyperinsulinemiaandimprovesthediversityofbeneficialgutbacteria.41,42Whenprocessedcarbohydratesarereplacedwithresistantstarch(ex:oats,rawpotatostarch,cookedandcooledrice,greenbananas),themicrobialprofileisaltered

40 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4139807/ 41 https://www.ncbi.nlm.nih.gov/pubmed/22686435 42 https://www.ncbi.nlm.nih.gov/pubmed/26196489

topromotethegrowthofanti-inflammatorymicroorganismsalongwithdecreasingthepro-inflammatoryones.43Paleolithicdiet:APaleolithic(Paleo)diettodaymimicsthedietofourancestorsduringtheOldStoneAge.Thisstyleofeatingwasprevalentduringthecourseofhumanexistence.44ThePaleodiettodayconsistsof:(1)Highconsumptionoffruits,vegetables,andvariousherbsandspices;(2)Moderate-to-highconsumptionofmeats,organs,fish,andeggs;(3)Moderateconsumptionofnutsandseeds;and(4)Exclusionofallprocessedfoods,legumes,grains,dairyproducts,andprocessedvegetableandseedoils(exceptoliveandcoconutoil).Thepaleodiethasbeenshowntobesuperiortootherformsofeatingstyles.45,46Mostimportantly,theeliminationofgrains,processedsugars,andlegumeshasbeencriticaltothesuccessofthepaleodietsincethesesubstanceshavebeenshowntodamagetheintestinalbarrierepitheliumandtopromoteauto-immuneandinflammatorychronicdiseases.47,48,49Thepaleodietalsoprovidesthefibersthatarecriticalforthemicrobiometofunctionandimprovediversity.50ItisimportanttonotethatthelossofdiversityinthegutmicrobiomewithresultingdysbiosisinWesternsocietieswhoconsumelargequantitiesofover-processedgrainproducts,legumes,processedsugars,andprocessedseedandvegetableoilscanbecounteractedbyreturningtoamodernpaleolithicdietcomposedofunprocessedfoods.51Forexample,inNovember2017,GaureeG.Konijeti,MD,MPH,andherresearcherspublishedapaperinthejournalInflammatoryBowelDiseases.52Thestudyinvolved15patientswhowerelivingwithactiveCrohn’sdiseaseorulcerativecolitisforanaverageof19years.Halfofthegroupwereonprescriptionmedicationstoattempttocontroltheirdisease.The15individualswereplacedonaPaleoautoimmuneprotocol(AIP)diet.Thedietremovedgrains,legumes,dairy,refinedseedoils,refinedsugar,eggs,nightshades,coffee,alcohol,nuts,andseeds.Byweek6ofthisautoimmunediet,11ofthe15patients(76%)hadremissionoftheirIBDsignsandsymptoms.A76%successraterivalsmostdrugtherapiesforinflammatoryboweldisease.Thestudylasted11weeks.Thenin2019,theauthorspublishedadditionalresultsfortheseparticipantsregardingtheirqualityoflifefollowingtheautoimmunediet.53Theanalysesrevealedthattheparticipantsinthestudysignificantlyexperiencedimprovementintheirclinicalsymptoms,bowelmovementfrequency,andqualityoflifewithinthe11weeksofthestudy.

43 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5409670/ 44 https://www.ncbi.nlm.nih.gov/books/NBK482457/ 45 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3402009/ 46 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4588744/ 47 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3402009/ 48 https://www.researchgate.net/publication/228866917_The_Western_diet_and_lifestyle_and_diseases_of_civilization 49 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3705319/ 50 http://jevohealth.com/cgi/viewcontent.cgi?article=1055&context=journal 51 https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0220619 52 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5647120/ 53 https://www.ncbi.nlm.nih.gov/pubmed/31832627

Ketogenicdiet:Ketogenic(keto)dietsrepresentanextremelylow-carbohydratediet.Aketodietreducescarbohydrateintaketolessthan50g/day.Atthislevel,insuliniskepttolowlevelsandcortisollevelsareslightlyelevated.Thiswillinducetheproductionofketonebodiesintheliver.Aketodietwillpromotemetabolichealthandprotectagainstcancerandothernon-communicablechronicdiseases.

Themechanismofactionappearstobe:(1)loweringinsulinlevels;(2)enhancingmitochondrialfunction;and(3)specificanti-oxidativeandanti-inflammatoryeffects.54Ahighintakeofmono-unsaturatedfattyacidsandn-3PUFAsaswellasnon-starchyvegetableswouldbebeneficialforpromotingguthealth.Ketogenicdietshavebeenshowntoinhibitcancercellglycolysisandproliferation.55,56Recentmedicalresearchhasshownthataketodietwouldimprovethegutmicrobiomeandreversedysbiosisinpatientswithautism,multiplesclerosis,andepilepsy.57,58,59CarnivoreDiet:AsIdiscussedearlier,researchersdeterminedfromfossilremainsthatNeanderthalMan60wasmostlycarnivorousaswellasHomo Sapien ancestors61 300,000 years ago were mostly meat eaters.So,thecarnivoredietisnotsonew.Asamatteroffact,apaperwaspublishedin1979titled,“TheImportanceofAnimalProductsintheHumanDiet”.62Thecarnivoredietissimilartoaketogenicdietbutwithallfruits,vegetables,nutsandseedsremoved.Aketogenicdietreducescarbohydratesandincreaseshealthyfatstoalevelwherethebody’smetabolismshiftsawayfromburningcarbstoburningfatandketonesforenergy.Thecarnivoredietrequireseatingonlywild-caughtandpasturedanimalsfromnose-to-tail.Sincethecarnivoredietcompletelyeliminatesallplants,itimportantlyavoidstheabundanceofantinutrients(i.e.lectins,oxalates,andphyticacid)foundinplants.Lectinsareproteins,whichplantsproducetodefendthemselvesagainstanimalstryingtoeatthem.Lectinscancausedigestiveupset,particularlywheneatenraw.Theseproteinsarefoundinroots,stems,leaves,andespeciallyintheseedsofmanyplants.Afterweeatlectins,theybindtothesugarportionsofourintestinalwallwheretheyinterferewithdigestionandnutrientuptake.However,afteredibleseedsarecookedusingmoistheat,someofthedamagingeffectsofmanylectinsmaybereduced.Yet,thedangeroflectinsisreal.63

54 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5828461/ 55 https://www.ncbi.nlm.nih.gov/pubmed/28653283 56 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5842847/ 57 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5009541/ 58 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5488402/ 59 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5597508/ 60 https://www.academia.edu/463164/Isotopic_biogeochemistry_13C_15N_of_fossil_vertebrate_collagen_application_to_the_study_of_a_past_food_web_including_Neandertal_man 61 https://www.ncbi.nlm.nih.gov/pubmed/28593953 62 https://www.journalofdairyscience.org/article/S0022-0302(79)83366-4/pdf 63 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6603809/

Oxalatesaretinymoleculesfoundinavarietyofseeds,nutsandmanyvegetables.Theywillbindmineralslikecalciumandformcrystals.Oxalatesalsocancausekidneystonesandareresponsibleforawidevarietyofotherhealthproblemsrelatedtoinflammation,autoimmunity,mitochondrialdysfunction,mineralbalance,connectivetissueintegrity,urinarytractissues,andpoorgutfunction.SallyK.Nortonwroteanexcellentarticleaboutthehealthhazardsofoxalates.64Medicalresearchalsohasshownthatoxalatespromotethetransformationofnormalbreastcellsintohighlymalignantandundifferentiatedtumors.65Specifically,oxalateshavebeenshowntodamagemitochondria.66Andmitochondrialdysfunctionisaprimarycomponentinthedevelopmentofcancer.67Phyticacidisauniquenaturalsubstancefoundprimarilyinplantseeds.Alledibleseeds,grains,legumesandnutscontainitinvaryingquantities,andsmallamountsarealsofoundinrootsandtubers.Theproblemwithphyticacidisthatitimpairstheabsorptionofiron,zincandcalciumandmaypromotemineraldeficiencies.68Specifically,phyticacidreducesmineralabsorptionduringthemealbutdoesn'thaveanyeffectonsubsequentmeals.Whilefoodpreparationbysoaking,sprouting,andfermentationcanreducethephyticacidcontentinmanyfoods,ifyoueathigh-phytatefoodswithmostofyourmeals,mineraldeficienciesmaydevelopovertime.Therefore,phyticacidisreferredtoasananti-nutrient.

Reportsofcasestudies:

• Acasestudypublishedin2016demonstratedthatapaleolithic-ketogenic(paleo/keto)diethealedaseverecaseofCrohn’sDisease.ThepatientstartedthedietinJanuary2015andcompletelyexcludedfruitsandvegetablesinNovember2015fortheremainderofthestudy.69

• Anothercasestudyin2016waspublishedofa60-yearoldpatientwhohadamalignantmyoepithelialtumorofthesoftpalate.Thepatientrefusedconventionalchemotherapyandradiationtreatment.Instead,thepatientstartedapaleo/ketodietinDecember2014.Forthefirstsixmonths,thepatientfollowedastrictmeatandfatonlydiet,whichwasessentiallythecarnivorediet.FromJuly2015on,shewasallowedtoeatsmallamountsofvegetableslessthantwotimesaweek.Surprisingly,thecancerprogressionwashaltedasevidencedbyimagingfollow-up.After20monthsandtheconclusionofthecasereport,thepatienthadnosymptomsorsideeffectsfromtheoriginallydiagnosedcancer.70

• Anothercancerpatient,AndrewScarborough,wasdiagnosedwithanaggressiveandincurablebraintumor(Grade3AnaplasticAstrocytoma)attheageof27.Heelectedtotreathiscancerwithastrictpaleo/ketodiet,whichhemodifiedintoa

64 https://jevohealth.com/cgi/viewcontent.cgi?article=1085&context=journal 65 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4618885/ 66 https://www.sciencedirect.com/science/article/pii/S2213231717307565 67 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4950268/ 68 https://www.ncbi.nlm.nih.gov/pubmed/19774556 69 http://www.ijcasereportsandimages.com/archive/2016/009-2016-ijcri/CR-10690-09-2016-toth/ijcri-1069009201690-toth.pdf 70 http://pubs.sciepub.com/ajmcr/4/8/8/

strictcarnivorediet.Twoyearsafterhisdiagnosis,hiscancerwasinremission.AndhisprotocolandresultsarebeinginvestigatedbyHammersfordHospitalinAustralia.71

Someofthepotentialbenefitsofacarnivoredietare:1. Restrictscaloriesandmimicsfasting:Proteinisfilling,soyoueatless.Eatingless

reducescaloricintake.Reducingcaloricintakewilldecreaseinsulinproduction,insulin-likegrowthfactor,andgrowthhormone.Fasting(whichrestrictscaloricintakeforaperiodoftime)triggersautophagywhereoldcellsdieanddamagedcellsrepair.Theendresultisreducedinflammationaswellasreducedsymptomsofchronicandautoimmunediseases.

2. Provideslowresidueingut:Thisdietisbasicallyproteinandfat–allofwhichareabsorbedintheupperpartofthegut.So,thereislittleleftoverresiduetoirritateorinflamethelowerportionsofthegut.Lessresidueinthelowergutreducesdiarrhea,bloating,gas,andabdominalpainwhilehelpingpreventinflammatoryboweldiseaseandirritablebowelsyndrome.Also,thecarnivoredietavoidsoxalatesandlectinsthatcouldbedamagingtothebody.

3. Altersthegutmicrobiome:Ahealthygutmicrobiomeisvitalforoptimumimmunehealthandreductionofinflammatorydiseases.72However,alteringthegutmicrobiomemayhavepositiveaswellasnegativeeffects.73Microbialdiversityandhomeostasisarekeytoahealthymicrobiome.

4. Suppliespre-digestednutrients:Eatingananimalfromnose-to-tailprovidesallthenutrientsthatsupportthatanimal’shealth.Thenutrientsthatareconsumedbytheanimalarepresentintheirmuscles,fat,cartilageandcollagenousparts,andtheirorgans.Eatingwildcaughtorpasturedanimalsfromnose-to-tailprovidesuswithallthesenutrients,whichmaybeinsufficientquantityandqualityforustothrive.74

5. Createsketones:Acarnivoredietwillputthebodyintoastateofketosis.Ketosiswillshiftthebodytoburningfatorketonesforenergyinsteadofburningglucose.Cancercellscannotutilizeketones,butourremaininghealthycellscan.AsImentionedabove,cancerpatientsmighthavesignificantresultsfrombeinginastateofketosiseventhoughtherearenolong-termhumanstudiestosupportthis.75

InflammationInflammationbyitselfisnormalandisnecessaryforahealthybodytofunctionandheal.Inflammationisaresponsetoapathogenicevent.Relentlessinflammationisaseriousprobleminthatthecauseoftheinflammationremainselusive,persistent,anddestructive.So,whenholesinthegutliningoccurregularlyfromcontinuousreintroductionofunhealthyfoodchoicesaswellasotherirritantsthatcouldfurtherdamagethegutlining,

71 https://www.openfuture.biz/expertise/AndrewScarborough.html 72 https://www.ncbi.nlm.nih.gov/pubmed/23618829 73 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3957428/ 74 https://carnivoremd.com/what-to-eat-on-a-carnivore-diet-your-carnivore-diet-meal-plan/ 75 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5450454/

inflammationbecomesconstant.Constantinflammationisstressful,destructiveandcanaffecttheentirebody,inducingdamagetoanyorganortissueanywhereinthebody.Acuteinflammation:Thisistheresponsetovarioustypesoftrauma.Itinvolvesthevascularsystem,theimmunesystem,andthecellsthatwereinjured.Variousinflammatorymediatorscausevasodilationallowingforbloodtoflowtotheinjurysite.Thebloodvesselsbecomemorepermeable,allowingtheplasmaandleukocytestoflowthroughthevesselwallsandintotheinjuredtissuetobeginahealingprocess.Themovementofplasmaintotissuecausesfluidbuildupandswelling.Allofthisisnecessaryforproperhealing.Theacuteinflammatoryresponseshouldbeshortandspecific.Theprocessbreaksdownthetissue,targetsthedamagedtissueandinvadingpathogens,andthenbuildsitbackup.Chronicinflammation:Ifthetriggersthatcausedanacuteinflammatoryreactionarenotremoved,thentheinflammationbecomeschronicanddestructive,alsoultimatelydegradingthegutmicrobiome.Whenthegutmicrobiomebecomesunhealthy,theimmunesystemishyper-activatedandhypersensitiveastheguthousesthebulkofthehumanimmunesystem.Thetoxicsubstancesthattriggergutdysbiosiscanalsotriggertheabnormalreleaseofzonulin,aproteinthatmodulatesthepermeabilityoftightjunctionsbetweencellsofthewallofthedigestivetract.76Overproductionofzonulinwillcausetheepithelialliningoftheguttobeincreasinglypermeable(i.e.leakygut).Theresultisthespreadofchronicsystemicinflammation.Throughacomplexsystemthatisnotcompletelyunderstood,althoughapparentlyinvolvingimmunehyperactivationandhypersensitivity,theimmunesystemmaygohaywire.Inotherwords,theimmunesystemcouldbegindestroyinghealthytissuesinthebodyinadditiontotheforeigninvaders.Theresultisknownasautoimmunedisease.77

GlutenGluten,whichcontainslectinsmentionedpreviously,isafamilyofproteinsthatispresentinwheat,rye,barley,andsomeothertypesofgrains.Glutenimpartsagreater“pliability”tothetextureoffoodsandisusedtoimprove“mouthfeel”.Productsthathavehighglutencontentorextraaddedglutenhaveimprovedtextureformorepleasurablemouthfeel,likebagels,high-glutenbread,andpastaproducts.Asamatteroffact,glutencouldbeaningredientinmanyprocessedfoods,cosmetics,prescriptionmedications,andnutritionalsupplements.Thehumanbodycannotcompletelydigestgluten.Oneoftheremnantsoftheincompletedigestionofglutenisgliadin.

GliadinGliadin,whichalsocontainslectins,hasthepotentialtoslowlyanddeliberatelydestroyvarioustissuesofthebody.Itseffectsarecumulative,producingchronicinflammationover

76 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3943850/ 77 https://onlinelibrary.wiley.com/doi/full/10.1111/joim.12395

time.Itcausesdysbiosisandopensholesinthegutlining,allowingsubstances,especiallyundigestedproteins,toleakintothebloodstreamthatshouldneverbethere.Researchershaveproventhisdamagetothegutliningoccursineveryhumanwhenevergliadinispresentintheintestines.78Gliadincausesachemicalreactionintheintestinalwall.Itincreasesthereactivityofzonulin.AsImentioned,zonulinisaproteinthatcausesthecellsoftheintestinalwalltoopenandclosenormallytoallowdigestednutrientstopassintothecirculatorysystem.However,excessivestimulationofzonulinwillcausethegutliningcellstoseparate,openinguplargeportalstothebloodstream.Ascellsintheone-cell-layer-thickliningofthegutseparatetoowidelyandfortoolongaperiodoftime,undigestedparticlesoffood,bacteria,andtoxicsubstancescanleakthroughtheopeningsintothebloodstream.79However,thehumanbodyisresilient.Thecellsoftheintestinalwallrepair,andtheyreplacethemselvesevery4-5days.80Ifglutenorotherirritantswerenotreintroducedintothedietagain,thenlikelytherewouldbenopermanentdamagefromthisone-timeoccurrence.Buttheproblemisaprocessofrepetition–constantlyconsumingglutenaswellasbeingexposedtootherirritants.

LeakyGutUnhealthyleakagefromtheintestinesintothebloodstreamisknownasincreasedintestinalpermeability(i.e.leakygut).Apreponderanceoftheevidenceindicatesthatgliadinisoneofthetriggersthatcanbreakdownthegutliningandincreasetheovergrowthofharmful,mostlyanaerobicbacteria.Whenundigestedparticlesoffoodortoxicsubstancesgetintothebloodstreamthatnevershouldbethere,theimmunesystembecomesactivated.Theimmunesystemislikeanarmythatiscalledintobattle.Theimmunesystem’spurposeistogetridofforeignelements.Theprocesstoridthebodyofirritatingsubstancesusuallybeginswithinflammation.Theinteractionbetweenhostgenetics,immuneresponse,gutmicrobiomeandfunction,andexposuretoenvironmentaltriggersiscriticalinthebreakdownofthemucosalimmuneresponseleadingtothedevelopmentofchronicinflammation.Arecentstudyhasshownthatgutepithelialbarrierdysfunctionplaysavitalroleintheinitiationofinflammation.81Increasedintestinalpermeabilityispresentinthepathogenesisofseveralchronicdiseasesincludingobesity,diabetes,anddiseasesofthebrainandthenervoussystemsuchasParkinson'sdisease,multiplesclerosis,andtheautismspectrumdisorders.82,83,84,85,86,87

78 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4377866/ 79 https://www.frontiersin.org/articles/10.3389/fimmu.2019.02233/full 80 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2965634/ 81 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6233106/ 82 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3049113/ 83 https://www.ncbi.nlm.nih.gov/pubmed?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17989107 84 https://www.ncbi.nlm.nih.gov/pubmed?Db=pubmed&Cmd=ShowDetailView&TermToSearch=27604608 85 https://www.ncbi.nlm.nih.gov/pubmed?Db=pubmed&Cmd=ShowDetailView&TermToSearch=27270497 86 https://www.ncbi.nlm.nih.gov/pubmed?Db=pubmed&Cmd=ShowDetailView&TermToSearch=20683204 87 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5129651/

In2000,AlessioFasano,MD(anexpertonautoimmunediseaseandzonulin)publishedresearchdemonstratingthatthedevelopmentofautoimmunediseasesisaresultofthreefactors:(1)geneticpredisposition,(2)environmenttriggersthataremismanagedbytheimmunesystem,and(3)breakdownintheintestinalbarrierfunctionsecondarytotheactivationofthezonulinpathwaybyfood-derivedenvironmentaltriggersorchangesingutmicrobiota.Geneticpredispositioncannotbecorrectedbytoday’stechnologies.Moreover,ifenvironmentaltriggerscanbeeliminated,ifthegutmicrobiomecanberestoredtohomeostasis,ifinflammatoryfoodchoicescanbeavoided,andiftheintestinalbarriercanberepairedandrestored,thenautoimmunediseasescouldbearrested.88,89,90,91However,in2002,Bagchietalpublishedresearchinwhichamechanismofautoimmunityininflammatorydisorderswasdescribedingreaterdetail.Essentially,theresearchdemonstratedthatchronicinflammatorydisorders(rheumatoidandosteoformsofarthritisinthisresearch)areinitiatedbyaninabilitytoformtheperfect3-dimensionalglycoproteinstructuresofTypeIIcollageninconnectivetissuesandtheIgGimmunesurveillancemolecules.Theidentityofthesestructureswentfrombeingidentifiedas3-dimensioinallycompetentandbiologicallyusablestructurestobeingunwelcomedforeignantigenicinvaders.92Therefore,thisnowcorrectclassificationinducedanupregulated“outofcontrol”immuneattackontheconnectivetissuesofthebody.Essentially,theautoimmuneresponsewascausedbyamanufacturingerrorthatinstigatedtheexcessiveimmuneresponse.ThisexplanationprovidesgreatermechanisticdetailandinsighttothesecondandthirdfactorsreportedbyDr.Fasano.

OtherIrritantstotheGutThegutmicrobiome,theintestinalmucouslayer,andtheepithelialliningofthegutbecomedamagedfrommanydifferentinfluences.Someoftheseirritatinginfluencesare:

• Stressesonthebody(includingemotional,physical,orchemical)couldbeseriousbutunrecognizedcauses.93,94,95Asignificantchemicalstresstothegutisglyphosateherbicide(Roundup)thatdamagestheDNAinhumancells;derangesglycoproteinsynthesis,structureandfunction;inhibitsthegrowthofhealthybacteria,anddirectlycausesleakygut.96,97Inaddition,stresstotheimmunesystemfrommetalionsleakingfromtitaniumimplantsplacedinthebodyandchemicalsleakingfrom

88 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3384703/ 89 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396758/ 90 https://www.ncbi.nlm.nih.gov/pubmed/22109896 91 https://www.physiology.org/doi/full/10.1152/physrev.00003.2008 92 https://www.ncbi.nlm.nih.gov/pubmed/12837047 93 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5879702/ 94 https://onlinelibrary.wiley.com/doi/full/10.1111/apt.12269 95 https://www.ncbi.nlm.nih.gov/pubmed/28336545 96 http://www.mdpi.com/1099-4300/15/4/1416/htm 97 https://oehha.ca.gov/media/downloads/crnr/032817tobelistedglyphosate.pdf

breastimplantscancausechronicsystemicinflammation,damagingthegutmicrobiome.98,99,100

• Stresstothebodyalsoincludesheavymetaltoxicity101,overexercising102,103,sleepdeprivationandsleepapnea104,continuousexposuretodirtyelectromagneticfields105,disturbancesincircadianrhythm106andexcessiveblue-lightexposureespeciallyintheevening107,andlackofpropersunlightthatisessentialfortheproductionofvitaminD3108–justtonameafewoffenders.

• Overlyprocessedvegetableandseedoils,hydrogenatedandpartially-hydrogenatedoils,processedsugars,orotherjunkandchemicalsinfoodswillhaveaharmfuleffect.109

• Allplantfoodshavethepotentialtoirritatethegutbywayoftheiranti-nutrients.Substanceslikephytates,oxalates,andlectinsthatexistinplantscoulddamagetheintestinalbarrier(discussedearlierinthesectionHealthyDiets&TheGut–CarnivoreDiet).Eliminatingallplantfoodsforaperiodoftimecouldassistthegutinhealingitself.Then,plantfoodscouldbereintroducedindividuallyandslowlylater.Oranindividualcouldcontinueforlifeonananimal-baseddietasIdescribedearlierinthispaper.

• Specificmedicationssuchasnon-steroidalanti-inflammatorydrugs(NSAIDs),corticosteroids,alcohol,narcotics,antibiotics,chemotherapydrugs,hydrogenperoxide,andbirthcontrolpills(tonameafew)couldresultinleakygut.110,111,112,113,114,115,116

• Low-doseionizingradiationhasacumulativeharmfuleffect.Inoursociety,frequentandunnecessarydentalandmedicalx-raysoverthecourseoftimecancause

98 https://www.ncbi.nlm.nih.gov/pubmed/31134756/ 99 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6223170/ 100 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5406475/ 101 https://www.sciencedirect.com/science/article/pii/S0160412018323183 102 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1332084/ 103 https://www.ncbi.nlm.nih.gov/pubmed/24882154 104 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6465302/ 105 https://www.ncbi.nlm.nih.gov/pubmed/28956351 106 https://www.ncbi.nlm.nih.gov/pubmed/32051239 107 https://www.ncbi.nlm.nih.gov/pubmed/27793218 108 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6116667/ 109 https://www.mdpi.com/1422-0067/20/10/2432/htm 110 https://onlinelibrary.wiley.com/doi/full/10.1111/apt.14451 111 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6108420/ 112 https://link.springer.com/article/10.1007/s00213-019-5185-8 113 https://www.arcr.niaaa.nih.gov/arcr382/article01.htm 114 https://www.sciencedirect.com/science/article/pii/S2213231717309163 115 https://onlinelibrary.wiley.com/doi/full/10.1111/adj.12425 116 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4939477/

damagetothemicrobiome,itsmetabolites,andtheepitheliallining.Researchonmicepublishedin2016showeddamagetothegutfromlow-doseradiation.117

• Anythingthatdisturbsthedelicatebalanceofmicrobesinthegutcouldbetheculprit.118

ACloserLookintotheInnerTubeoftheGut119Thegardenofmicrobesinthegutconsistsofacommunityofbacteria,fungi,archaea,protozoans,andviruses.Theepithelialbarrieroftheguthasanareaof400 m2andisexternaltothebody.Itislikethe“holeinadoughnut”.Themicrobialcellsareeitherfloatingintheintestinallumen,adheringtothemucouslayer,oradheringtothesurfaceoftheepithelialcells.120Themicrobiomefromthevaginaltractatbirthpopulatesinthegut.However,inthecaseofcesarean-sectiondeliveredbabies,themicrobiomeissimilartotheskinmicrobiome.121Duringbreastfeeding,humanmilkcontributestothegutmicrobiomeandthedevelopmentoftheimmunesystem,especiallyduringthefirstfewdayswiththecontributionofcolostrum.Astheactivemicrobialcommunitydevelops,itwillinteractwiththehost.Themicrobiomeaffectsnormalgutdevelopmentmainlythroughtheshort-chainfattyacids(SCFA)creationbythemicrobiome.SCFAplayananti-inflammatoryroleandsupportintestinalhomeostasisthroughcellularproliferation,differentiation,andinhibitionoftheproliferationofcancerouscells.Thebeneficialmicrobiomestimulatesnonspecificandspecificimmunesystemdevelopmentandinhibitstheadherenceofvariouspathogens.Itisimportanttonotethatahealthygutmicrobiomehelpssynthesizemanyvitamins,suchasB1(thiamine),B2(riboflavin),B5(pantothenicacid),B6(pyridoxine),B7(biotin),B9(folate),B12(cobalamin),andK.Inaddition,itdegradesxenobiotics,sterolsandcausesbiliaryacidsdeconjugation.122Ifthehomeostasisofthisbeneficialmicrobiomeisdisturbedandbecomesdysbiotic,thentheultimateresultisthedevelopmentofchronicdiseases.123Theintestinalepitheliallining,themucosalimmunesystem,anddiversityandqualityofthegutmicrobesareaffected.Thebodywillbecomemoresusceptibletoinfections,andtheimmunesystemmayreactagainstthebody’sowncells(autoimmunity).

Tohelpmaintainhomeostasis,theintestinalmucosalimmunesystemcontainsvarioussignalingpathways.Specificsensors,suchasPeyer’sPatches,recognizepathogens,commensalbacteria,andpotentialpathogens.Thesesensorsarepartofthehostdefense

117 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4867328/ 118 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5707675/ 119 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6104162/ 120 https://www.ncbi.nlm.nih.gov/pubmed/20664075 121 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2900693/ 122 https://www.ncbi.nlm.nih.gov/pubmed/25437605 123 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5050011/

system.Theimmunesystemwillcreateintestinalinflammationafteritrecognizespathogenicorpotentiallypathogenicmicrobesinthegut.124,125Thereisa“giveandtake”inthegut.Inahealthygut,themucosallayerresistsinvasionofunhealthygutbacteriaandinhibitsthereproductionofpathologicalspecies.Additionally,thegardenofbalancedbacteriainthegutmaintainsimmunetoleranceintheintestine.126Whentherearegeneticpredispositionsinthehost’simmunesystemtointestinalpathogens,thesecanbeoverriddenbychangingthediettoagut-friendlydiet,whichwillrestorethehumoralimmunityandinhibitthepathologicalbacteria.127

AsImentioned,themucosalimmunesystemconstantlyoverlooksthegutmicrobiome.Anydisruptioninthegutmicrobiomewillelicitanimmuneresponse.Forexample,whenthedietislackinginhealthyfibers,whicharethefoodsourceofthegutbacteria,gutbacteriabegintodamagethemucouslayertofindtheirnourishment.Theultimatedamagetothemucouslayerpromotesgreaterepithelialaccessandlethalcolitisbyvariousmucosalpathogens.128Inindividualswithdysbiosis,thegutmicrobiomecommunicateswiththegutepitheliallayertotriggerantimicrobialsubstancestoattackthepathologicinvaders.129,130Chronicdysbiosiswillencourageexacerbatedautoimmuneandinflammatorydiseases.131Ultimately,thiswillleadtochronicinflammation,mucosalbreakdown,andtissuedamage.Theimmunesystembuildsitsinnateresponsesanditsabilitytoregulateautoimmuneandinflammatorydiseasesearlyinlife.132,133,134Whenthehostexperiencesvariousmicroorganismsinthefirstfewyearsoflife,theintestinalmucosalimmunesystemlearnstoreactappropriately.135,136Toll-likereceptors(TLRs)fromthemembraneoftheepithelialandlymphoidcellsofthesmallintestineareinvolvedinthisdifferentialrecognition,beingresponsibleforthenormaldevelopmentoftheintestinalmucosalimmunesystem.TLRssuppresstheoccurrenceofaninflammatoryresponseandpromoteimmunologicaltolerancetonormalmicrobiotacomponents.

124 https://www.ncbi.nlm.nih.gov/pubmed/22179258 125 https://www.ncbi.nlm.nih.gov/pubmed/?term=Evolutionary+dynamics+of+bacteria+in+a+human+host+environment 126 https://www.ncbi.nlm.nih.gov/pubmed/21530739 127 https://www.ncbi.nlm.nih.gov/pubmed/28790160 128 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5131798/ 129 https://www.ncbi.nlm.nih.gov/pubmed/12548285 130 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2716667/ 131 https://www.ncbi.nlm.nih.gov/pubmed/20664075 132 https://www.ncbi.nlm.nih.gov/pubmed/29670252 133 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4007055/ 134 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5645538/ 135 https://www.ncbi.nlm.nih.gov/pubmed/?term=nnate+immune+recognition+of+the+indigenous+microbial+flora 136 https://www.ncbi.nlm.nih.gov/pubmed/27383981

ThegutmicrobiomeaffectsneutrophilmovementandfunctiontocausethedifferentiationofT-cellsintothevarioustypesofhelpercells(i.e.Th1,Th2,Th17)andalsointoregulatoryT-cells(Tregs).137TheTh17 cellssecretemanydifferentcytokines(IL-22,IL-17A,andIL-17F),whichhaveasignificantinfluenceonimmunehomeostasisandinflammation.138TheseTh17 cellsmaintainbothastimulatoryandaninhibitorycytokinefunction.139Ontheotherhand,regulatoryTcells,knownasTregs,activelymaintainimmunetolerance.Theymodulateanexcessivelyhighinflammatoryresponse.140IfTregsaremalfunctioning,theultimateresultsareautoimmunedisorders.141SecretoryIgA(SIgA)isthemainantibodyfoundinsecretionsofthemucouslayer.142Itisthefirstlineofdefenseinprotectingtheintestinalepitheliumfromenterictoxinsandpathogenicmicrobes.SIgAassistsintheremovalofantigensandpathogenicmicrobesfromtheintestinallumenbyblockingtheiraccesstoepithelialreceptors,entrappingtheminmucus,andcausingtheirremoval.Inthisway,SIgAfunctionsinmucosalimmunityandintestinalhomeostasis.143

GutMicrobiome&InfectionsThemicrobiomeholdsaprincipalroleintheinitiationandprogressionofinfectiousdiseases.144Ahealthygutmicrobiomewillpreventtheinvasionofpotentiallypathogenicmicrobesbycompetingwiththeseunfriendlybacteriaforadhesionsitesandnutrientsaswellasreleasingtoxicmoleculestocounteractthem.ThemicrobiomestimulatesthesecretoryIgAresponse.Also,thesignalingmoleculesreleasedbythemicrobiometriggerthedevelopmentofgranulocyte/monocyteprogenitorsinthebonemarrow,whichultimatelypromotethehostinnateresponse.Intheabsenceofthesesignalingmolecules,thereisanincreasedsusceptibilitytosystemicinfection.Theinteractionsbetweenthegutepithelialcellsandthegutmicrobiomearecrucialtomaintaingutbarrierhealth.Unfortunately,whendysbiosisoccurs,themicrobiomewillloseitsanti-infectiousbarrierqualityandthegeneralcirculationcanbeeasilyinfectedwithdifferentpathogenicmicroorganismsfromtheenvironment.Ongoingresearchshowsthespecificrolebetweenthegutmicrobiotaandtheimmunesystem.Theresearchhasfocusedoninfectiousdiseasescausedbymicrobiomemanipulation.Sincemicrobiotamanipulationcouldcontrolthebalancebetweenhealthand

137 https://www.ncbi.nlm.nih.gov/pubmed/25438024 138 https://www.ncbi.nlm.nih.gov/pubmed/24164337 139 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3965671/ 140 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3684415/ 141 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3337124/ 142 https://www.ncbi.nlm.nih.gov/pubmed/16362985 143 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3774538/ 144 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5570093/

infectiousdisease,intestinalmicrobiotaalterationbyapathogenorapathobiontcouldleadtochronicdiseases.145,146,147

CrosstalkBetweenMicrobesAllbacteriacommunicatewitheachotherbysignalingmolecules.Thisisaformofcrosstalk.Becauseofthis,bacterialcellscansensetheirenvironment,monitorthepopulationdensityandadjusttheirgeneexpression.Thus,bacteriagaintheadvantagetodisseminateandsurviveinhighlycompetitiveenvironments.Intercellularcommunicationisdividedintotwocategories,basedonthequorum-sensing(QS)mechanism.Thefirsttypeistheintraspecificcell-to-cellcommunicationthroughspecificQSmoleculesandthesecondmechanismconsistsoftheinterspecificcommunicationbasedonauniversalchemical“language,”whichprovidesinterspecificsignalingbetweenbacteriaandhostcells.TheQSmechanismallowsbacteriatoregulatethehostcolonizationbycommensalbacteriaandtomodulatethehostresponse.148,149,150Quorum-sensingisalsousedbymicrobestodetectthepresenceofothersimilarmicrobes.151Inaddition,specificintestinalhormonescanmimictheactionofbacterialsignalingmolecules,whichincreasesthecomplexityofcrosstalkbetweenthebacteriaandthehost.152

Thegutmicrobiomecommunicatesbidirectionallywiththecentralnervoussystembyproducingandsensingneurochemicalsthatarederivedeitherwithinthemicroorganismsthemselvesorwithintheirhost.153Also,thegutmicrobiomecanproduceneurochemicalswithhormonalactivitiesthatcouldgobeyondthegutandaffectchangesinanxiety,depression,cognition,pain,inflammation,autoimmunity,andmetabolicdiseases.154,155,156,157

ChronicInflammatory&AutoimmuneDiseasesChronicinflammationisevidentatthebeginningofpracticallyallchronicdiseasesandautoimmunediseases.Chronicandautoimmunediseasesoccurwhen(1)thegutbecomesoverlypermeableonaconstantbasis,(2)chronicinflammationprevailsandpermeates

145 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4310462/ 146 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3942874/ 147 https://www.ncbi.nlm.nih.gov/pubmed/29718124 148 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC99016/ 149 https://www.ncbi.nlm.nih.gov/pubmed/15953193 150 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3543102/ 151 https://www.ncbi.nlm.nih.gov/pubmed/15055923 152 https://www.ncbi.nlm.nih.gov/pubmed/11929534 153 https://www.ncbi.nlm.nih.gov/pubmed/24997027 154 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3232439/ 155 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5219689/ 156 https://www.ncbi.nlm.nih.gov/pubmed/21387369 157 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5528863/

throughthebloodsystembymeansofvariouselementsoftheinflammatorycascade,(3)ageneticweaknessinsomeremotetissuereactstothischronicinflammation,and(4)theconfusedimmunesystemstartstoattackhealthytissues.Inthecaseofgluten,gliadininitiatesthedamagetothegutlining.AsIalreadydiscussed,itisimportanttonotethatotherirritantsfromvarioussourcesdocausedamagetothegutliningandtogutbacteriaaswell.Anabundanceofvariousirritantstothegutincreasesthepotentialforchronicinflammation.Oncechronicinflammationpersists,chronicandautoimmunediseasesbegintomanifest.

Themanifestationofchronicorautoimmunediseasescouldtakeyearstodevelopfromrepeatedinsultstothebody.Apersonprobablywouldnotknowthesedestructivechangeswereslowlyoccurring.Asamatteroffact,apersonwouldnotneedtoexperienceobviousgutsymptomssuchasdiarrhea,constipation,bloating,orpain.Aleakygutfrequentlydoesnotcausegutsymptoms.Assubclinicalandfrequentinsultsaccumulateovertime,diseasemayonlymakeitselfknownmanyyearsafterthefirstinsultoccurredlongago.Anotherfactortobeconsiderediswhenchildrenundertheageof5 yearslivingindevelopedcountriesarenotexposedtomanyenvironmentalmicrobes,compounds,andantigens.Thislackofearlyimmunestimulationcouldcausemalfunctioningoftheimmunesystemandleadtohypersensitivity,hyper-reactivity,autoimmunedisease,orinflammatorydiseaseslaterinlife.

Belowisadiscussionofavarietyofchronicdiseases:

PeriodontalDiseasePeriodontaldiseaseisoftenconsideredacausalfactorformanychronicdiseases.Youneedtoknowthecompletestory–notjustpartofit.Whileperiodontaldiseasecouldbeanidusforchronicsystemicinflammation,thisisonlypartofthestory.ThestoryhasaBeginning,aMiddle,andanEnding.Let’sstartinTheMiddle.

TheMiddle

Dentalplaqueishealthyuntilit’snothealthy.158Periodontaldiseasedevelopsfromunhealthydentalplaque.Unhealthyplaqueresultswhenhealthyplaqueistransformedintounhealthydentalplaquebecauseofanunderlyingcompromisedimmunesystemandunhealthyfoodchoices.It’sfundamentalforyoutoappreciatethatacompromisedimmunesystemhasitsrootsinunhealthychangesinthegut(i.e.gutdysbiosis)159,160,whichcauseschronicsystemicinflammation.

158 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4132376/ 159 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892391/ 160 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5937375/

Acompromisedimmunesystemandunhealthyfoodchoicescouldallowthehundredsofbacteriaindentalplaquetogetoutofbalanceandbecomeunhealthy.161,162Then,unhealthybacteriacouldproliferateandcausetheprogressionofadvancedgumdisease163.OneofthemostvirulentbacteriainperiodontaldiseaseisPorphyromonasgingivalis(P.gingivalis).164,165Amongotherself-protectivemeasures,thisbacteriumproducesabiofilm,whichisresistanttothebody’simmunedefenses.166AsthebodycontinuestofighttheresistantP.gingivalis,additionalchronicinflammationresults.Thischronicinflammationcancausethetissuessurroundingtheinfectedgumspacestobreakdownallowingtheirtoxicelementstoleakintothegeneralcirculation.Forexample,investigatorspublishedastudyin2020,whichdemonstratedhowP.gingivalisisimplicatedinnon-alcoholicfattyliverdiseasebyactivatinginflammatoryresponsesinhepaticcells.167Additionally,autoimmunitymayplayaroleintheprogressionofperiodontaldisease.168Itisimportanttoremoveunhealthyplaquethroughanefficientpersonaloralhygieneprotocolperformeddaily.However,itisalsocriticaltounderstandthatgutdysbiosisleadstopathologicalchangesinthehealthycommunityofbacteriainthemouth.Therefore,gutdysbiosismustbetreatedtorestoreoralhealth,alongwithremovingunhealthydentalplaque.Imustemphasizethatitisunhealthytoindiscriminatelykillbadbacteriaaswellasgoodbacteriainthemouthbyusingantimicrobialmouthwashesorantibioticsonadailybasis.169Italsoisvitaltobeawareofperiodontaldiseasebecauseitsprevalenceisatepidemicproportions.In2010,apublishedpaperdemonstratedthat93.9%ofadultsintheUnitedStateshadsomeformofgingivitis.170Andin2012,theCentersforDiseaseControlandPrevention(CDC)publishedtheirresultsintheJournalofDentalResearch.Thereportwasrecentlyupdatedin2015intheJournalofPeriodontology.171Itshowedtheprevalenceofperiodontitiswasestimatedtobe47.2%forAmericanadults(approximately64.7millionpeople).Foradults65yearsoldandolder,theprevalencejumpedto70.1%.ThesefindingsweretheresultofthemostcomprehensiveperiodontalevaluationperformedeverintheUS.So,staticallyyoumostlikelyhavesomeformofperiodontaldisease,anditmustbetreatedcompletely.Otherwise,onceperiodontaldiseaseisestablishedinthemouth,itspathologicalbyproductscanseepintothebloodstream,lymphfluid,andbonestructurestocausespreadofinfectionandinflammationtoallareasofthebody.Thismechanismofseepingintothebody’scirculationissimilartothewaythatanunhealthygutcauses

161 https://www.ncbi.nlm.nih.gov/pubmed/28476771 162 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5126660/ 163 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3653317/ 164 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4744328/ 165 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4276050/ 166 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4925967/ 167 https://www.ncbi.nlm.nih.gov/pubmed/31283861 168 https://www.ncbi.nlm.nih.gov/pubmed/?term=10.1016%2Fj.autrev.2016.09.013 169 https://www.ncbi.nlm.nih.gov/pubmed/28353075 170 https://www.ncbi.nlm.nih.gov/pubmed/?term=20437720 171 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4460825/

leakageoftoxicelementsintothebloodstream(i.e.leakygut)–bothcreatingchronicsystemicinflammation.Theeventualresultofchronicsystemicinflammationischronicdisease.172,173,174TheCentersforDiseaseControlandPreventionstatedthat60%ofAmericanslivewithatleastonechronicdisease,andchronicdiseasesareresponsiblefor70%ofdeathseachyearintheUnitedStates.175Therefore,periodontaldiseasecouldbeasourceofdegenerativechronicdiseasesoriginatingfromchronicsystemicinflammation.

TheBeginningInterestingly,therearethreehumanresearchstudiesthatshowedahealthydietalonecanimprovethehealthofthemouth.Thesestudiesalsodeterminedthatremovingdentalplaquebybrushingandflossingwasnotessentialtoimproveoralhealthaslongasdietwascorrected.Specifically,theinvestigatorsdemonstratedthatchangingfromadietabundantinhigh-processed-carbohydrateandinflammatoryfoodstoadietexcludinghigh-processed-carbohydrateandinflammatoryfoodswilldecreasesignsofguminflammation.176,177,178However,activeperiodontaltreatmentwillbenecessaryifguminflammationprogressesintoperiodontitis,whichdestroysthejawbonesurroundingtheteeth.InFebruary2019,amedicalresearcharticlewaspublishedinBiomedicalJournal179entitled,“Associationbetweenperiodontalpathogensandsystemicdisease”.Theauthorsdescribethecorrelationbetweenperiodontaldiseaseandvariouschronicdiseasesandoutcomessuchascardiovasculardisease,gastrointestinalandcolorectalcancer,diabetesandinsulinresistance,Alzheimer'sdisease,respiratorytractinfections,andadversepregnancyoutcomes.Theauthorsgoontostatethatthereareconflictingstudies,whichtrytoprovecausalrelationships.However,thereissignificantresearchtoshowastrongcorrelation.

InanotherarticlepublishedinAugust2019byHashiokaetal180,theauthorsreviewedmedicalresearchthatindicatesacausalrelationshipbetweenperiodontaldiseaseandvariousneuropsychiatricdisordersincludingAlzheimer’sdisease,majordepression,Parkinson’sdisease,schizophrenia,aswellastheneurologicaleventofischemicstroke.Theinitiatingcauseoftheseneurologicaldiseasesisneuroinflammation,whichisinducedbychronicsystemicinflammation.Periodontaldiseasecauseschronicsystemicinflammationbythereleaseofpro-inflammatorycytokinesandtheinvasionofperiodontitisbacteria(specificallyP.gingivalis)alongwiththeirinflammatorycomponents

172 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5520251/ 173 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5359961/ 174 https://www.ncbi.nlm.nih.gov/pubmed/28835673 175 https://www.cdc.gov/chronicdisease/center/index.htm 176 https://www.ncbi.nlm.nih.gov/pubmed/19405829 177 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4962497/pdf/12903_2016_Article_257.pdf 178 https://www.ncbi.nlm.nih.gov/pubmed/?term=10.1111%2Fjcpe.13094 179 https://www.sciencedirect.com/science/article/pii/S2319417018302634?via%3Dihub 180 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6695849/

(lipopolysaccharideorLPS)intothesystemiccirculation.Chronicsystemicinflammationwillactivatethemicroglia,theimmunecellsinthebrain,creatingneuroinflammation.ButIwanttoemphasizeagainthatsystemicchronicinflammationistheresultofaleakygutfromgutdysbiosisinmostcases.Inessence,myresearchsuggeststhatperiodontaldiseaseisnottheseedofallsystemicdisease.AsIsuggestedabove,periodontaldiseaseisjustoneofmanychronicdiseasesoccurringonthecontinuumofthespreadofchronicsystemicinflammationthatstartsinthegut.Sincethemouthisvisibleandeasytoexamine,themouthmaybethefirstclinicalareawherediseaseisdiagnosed.AndasImentionedearlier,theprevalenceofperiodontaldiseaseisatepidemicproportions.Oncesystemicdiseasespreads,aviciouscyclebeginsbecausealltissuesaffectallothertissuesinthehumanbody.Allmucosaltissuesuse“crosstalk”tocommunicatewithothertissues.181,182,183

Ishouldpointoutthatunhealthybacteriainthemouthinturncaninteractfurtherwithunhealthybacteriainthegut,andviceversa.184Inthecaseofperiodontaldisease,treatmentforcascadingchronicdiseasesmustincludehealingboththeunhealthygutandtheunhealthymouth.Butforthemostpart,theoriginationofmouthdiseaseisinthegutbeforebecomingvisibleinthemouthandotherareasofthebody.

TheEndingTostopperiodontaldiseaseandpreventthisinfectionfromenteringthesystemiccirculation,theinfectionmustbetreatedefficiently.Treatmentmayoftenconsistofadentist,hygienist,orperiodontistremovingirritantsthathavebecomelodgedunderthegumtissuesandinitiatinginflammationandinfection.Removingtheseirritantswillassistthebodyinhealing.185Inmoreadvancedstages,surgicalproceduresmaybenecessarytoarrestthisdisease.Whatevertreatmentisnecessary,aneffectiveoralhygieneprogramshouldbeinstitutedatafrequencybasedonthepatient’sabilitytotakecareofhisorhermouth.Theindividualalsomusthaveapersonaloralhygieneprotocoltomaintainahealthymouth.

Butwhateverperiodontaltreatmentisrequired,completetreatmentmustincluderepairingthegut,restoringthehealthybalanceofbacteriainthegut,andavoidingunhealthyprocessedfoodsandinflammatoryfoods.

Type1Diabetes

181 https://onlinelibrary.wiley.com/doi/abs/10.1111/cea.12723 182 https://www.ncbi.nlm.nih.gov/pubmed/?term=10.1016%2Fj.cyto.2017.01.016 183 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6266996/ 184 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5028810/ 185 https://www.ncbi.nlm.nih.gov/pubmed/31849397

Type1diabetes(T1DM)iscausedbythepatient’sinabilitytosecreteinsulinasaresultoftheautoimmunedestructionofthepancreaticbetacells.186ThepatientcouldhaveageneticpredispositionforT1DM187orbeexposedtoenvironmentaltoxicsubstances,whichcouldtriggertheproductionofantibodiesagainstthepatient’sbetacells.Also,alowdiversityofgutmicrobesandtheovergrowthofunhealthybacteriacouldbefactorsinthedevelopmentofT1DM.188Dysbiosisincreasesthepermeabilityoftheintestinalepitheliumbecauseofalossoftightbarrierfunction.Thenleakageintothecirculatorysystemofincompletelydigestednutrients(especiallyproteins)fromthedietandmicrobialantigenswilltriggerinflammationthatcouldleadtobetacellattackinthepancreas.189Inaddition,thelossofhealthycommensalmicrobesinthegutwillnegativelyinfluencethepatient’simmuneresponseallowingforincreasedpotentialforinflammationandbetacellattack.190Specifically,in2019Tangetal191suggestedthatthebestinterventionstrategyforT1DMmaybeacombinationofstrictglycemiccontrolthroughdietandimmunemodulationtoprotectβ-cellfunctionasearlyaspossible.Immunemodulationcouldbeenhancedbycreatingahealthygutmicrobiome.

RheumatoidArthritisThereisacorrelationbetweenrheumatoidarthritisanddysbiosis,suggestingthatdecreasedcommunicationbetweenthehostandthegutmicrobiomeisasignificantcontributingfactortotheinflammationofautoimmunediseases.192,193

CeliacDiseaseModificationofthenormalgutmicrobiotamayhavearoleinthedevelopmentofceliacdisease.Somespeciesofbacteriawerereducedinpatientswithceliacdiseasecomparedtohealthypeople.Thefucosyltransferase2(FUT2)generegulatestheexpressionofABHbloodgroupantigensinmucusaswellasotherbodysecretionsandalsoinfluencesthecompositionofmucosa-associatedbacteria.ABHantigensarecarbohydratestructuresthataresynthesizedinastepwisefashionbyglycosyltransferaseenzymes,i.e.fucosyltransferase2inthiscase,thatsequentiallyaddspecificmonosaccharidestoglycoproteinsandglycolipids.AmutationinFUT2geneimpairsstructuralandfunctionalcompetenceandcancauseadecreaseinbacterialdiversityandimbalanceinthegutmicrobiome.ThiscouldcauseanovergrowthofCandidaalbicans,forexample,whichisaculpritintheonsetofceliacdisease.194

186 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4138592/ 187 https://www.ncbi.nlm.nih.gov/pubmed/22005987 188 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4587635/ 189 https://www.ncbi.nlm.nih.gov/pubmed/22290506 190 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2551660/ 191 https://www.ncbi.nlm.nih.gov/pubmed/31849842 192 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3816614/ 193 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4969881/ 194 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4863046/

InflammatoryBowelDiseaseIBDistheacronymforinflammatoryboweldisease.Thistermrelatestoagroupofchronicintestinaldiseasescharacterizedbyinflammationofthelargeorsmallintestines.Themostcommontypesofinflammatoryboweldisease(IBD)areulcerativecolitisandCrohn’sdisease.IBDcreatesendotoxemia195,whichcompromisestheimmunefunctionandcontributestosystemicchronicinflammation.196

TheseverityofdysbiosisdeterminestheseverityofpathogenesisofIBD.InIBD,excessiveamountsofbacteriabuildupandadheretothegutmucosaandinvademucosalepithelialcells,incitinganinflammatoryresponse.InflammationleadstochangesinthecompositionofthegutmicrobiomewithanincreaseinaerobicbacteriaaccompaniedbyasignificantdecreaseinthefecallevelsofbutyricandpropionicacidinIBDpatients.TheunbalancedmicrobiomecontributestothedevelopmentofanoverproductionofhydrogenperoxideandIBD.197,198

AllergicDiseasesAlthoughsomegeneticfactorsaffectthedevelopmentofallergicdiseases,environmentalfactorsandgutdysbiosishaveasignificanteffect.199Reducedmicrobialdiversityininfancyiscorrelatedwithanincreasedriskforallergieslaterinlife.200Also,aStandardAmericanDietwithunhealthyfatscancausepulmonarydamage.201

SystemicLupusErythematosus(SLE)Systemiclupuserythematosusisasystemicautoimmunediseasewithunknownetiologycharacterizedbythepresenceofhyperactiveandaberrantantibodyresponsetonuclearandcytoplasmicantigens.202DysbiosisisassociatedwithSLE.203Forexample,inamousestudy,dysbiosisacceleratedthedevelopmentoflupus.204

Skin-RelatedAutoimmunePathologies

195 http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0170034&type=printable 196 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4707069/ 197 https://www.ncbi.nlm.nih.gov/pubmed/20224151 198 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3400418/ 199 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5292562 / 200 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4216641/ 201 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4103790/ 202 https://www.ncbi.nlm.nih.gov/pubmed/28721860 203 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4196225/ 204 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4249226/

Skinautoimmunediseasesarelinkedtodysbiosis.205Forexample,thegutmicrobiomedysbiosisinpsoriaticarthritiswassimilartothatofIBDpatients.206Anddysbiosiswasafactorinpatientswithsystemicsclerosis.207

NeurologicalInflammatoryDiseasesMedicalresearchhasprovedthatthegutmicrobiomehasanimpactonbraindevelopmentandfunction.Moreover,theguthousesmoreneurotransmitterreceptorsthanthebrain.Therefore,dysbiosisaltersanxiety-likebehaviorandalsoupregulatesthehypothalamicpituitaryadrenalsystemstressreactivity.Neuroactivebacterialmetabolitesaretransportedthroughthebloodstreamtothebrainandstimulateinflammation.208

DysbiosiscanleadtoinflammationthatisassociatedwithAlzheimer’sDisease209aswellasmultiplesclerosis.210Theseanaerobicpathologiesprovideopportunisticenvironmentsforanaerobes,suchasyeasts,worms,parasites,mold,andviruses,particularlytheherpesviralfamily,totakeupresidenceandpromoteinfectiouspathologies.

SystemicHypertensionInducedbyObstructiveSleepApneaObstructivesleepapneaandsystemichypertensionarecommonandinterrelateddiseases.Areviewofpeer-reviewedstudieswaspublishedin2019andshowedthatgutdysbiosiscouldcauseneuroinflammation,whichisahallmarkofthepathophysiologyofobstructivesleepapnea-inducedsystemichypertension.Theprocessappearstobethecreationoflow-gradeinflammationthroughdamagetothegutwallbarrierresultingin“leakygut”.Theresearcherssuggestedthatreversinggutdysbiosisatanearlystagethroughprebioticsandprobioticscombinedwithpositiveairwaypressuretherapymayopennewhorizonsoftreatmenttopreventsystemichypertension.211

CancerDysbiosisinfluencesnotonlyaninflammatoryresponse,butdigestionandothervitalfunctions.Indysbiosis,commensalbacteriachangeintopathogenicbacteria.Thesecansensitizetheguttocancerouslesionsbycausingcellproliferationandmutationleadingtotumorformation.212Thereisanincreaseinthepermeabilityofthemucosalsurfaces,whichinturnleadstointeractionsofthegutmicrobiomeandtheimmunecells.Allthisincreasesinflammation,whichisgenerallyaresponsetoanaerobicpathogensoroxygendeprivation,whichfurthersensitizesthehostforcancerprogression(ananaerobicpathological

205 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881942/ 206 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4280348/ 207 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5508636/ 208 https://www.ocl-journal.org/articles/ocl/abs/2016/01/ocl150036-s/ocl150036-s.html 209 https://www.ncbi.nlm.nih.gov/pubmed/28372330 210 https://www.ncbi.nlm.nih.gov/pubmed/28069755 211 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6778338/ 212 https://www.ncbi.nlm.nih.gov/pubmed/29073104

process).213Then,neighboringcellscouldbecomeeffectedastheysharethesameanaerobicbiologicalenvironment.Also,activationofM1macrophagesduringdysbiosiscausesthetoxicproductionofreactiveoxygenspeciesandreactivenitrogenintermediates,whichcanleadtothecreationofcancerouslesions.214Inaddition,dysbiosiscanchangethebloodestrogenlevelandcontributetotumordevelopment.215Manypathogenicbacteriaandvirusescanalterthecellcycleprogressionandinhibitapoptosis,thusincreasingtheproductionofcancerouscells.216

Gutdysbiosishasbeenrelatedtobreastcancer.Plaza-Díaz,etal217hypothesizedthattheriskofbreastcancercouldbeassociatedwiththecompositionandfunctionalityofthemammary/gutmicrobiota,andthatexposuretoenvironmentalcontaminantssuchasendocrinedisruptorcomponents(EDCs)mightcontributetoalterthegutandthebreastmicrobiome.

Additionally,Paridaetal218discussedtheprominentrolesofthegutmicrobiomeintheregulationofsteroidhormonemetabolismasthemostimportantriskfactorinbreastcancer.Gutmicrobesencodeenzymescapableofdeconjugatingconjugatedestrogenmetabolitesmarkedforexcretion,pushingthembackintotheenterohepaticcirculationinabiologicallyactiveform.Furthermore,theintestinalmicrobesbreakdownotherwiseindigestibledietarypolyphenolstosynthesizeestrogen-likecompoundsorestrogenmimicsthatexhibitvariedestrogenicpotency.Therefore,thepotentialroleofthegutmicrobiomeinbreastcancerisbymediatingmetabolismofsteroidhormonesandsynthesisofbiologicallyactiveestrogen.Interestingly,studieshaveshownthatincreasingbeneficialgram-positivebacteriainthegutcanenhanceTh1immuneresponsesandoffertherapeuticbenefitsbypromotinganticancerimmuneresponses.219,220Also,ahealthygutmicrobiomecanproducelargeamountsoffolate,whichplaysacrucialroleinregulatingDNAsynthesis,andotherantioxidant-involvedsubstancessuchasselenium,vitaminC,andvitaminA,whichhelppreventDNAlesions.Inaddition,thereareanti-tumoraleffectsfromlacticacidproducingbacteriaaswellasbutyrateproducingbacteria.221,222

Otherinterestingmedicalresearchissuggestingtheimmunotherapy,whichbooststhebody'snaturaldefensestofightcancer,mightbeenhancedifthegutmicrobiomeisdiverse

213 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529202/?report=classic 214 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4180221/ 215 https://www.ncbi.nlm.nih.gov/pubmed/?term=Estrogen+and+Microbiota+Crosstalk%3A+Should+We+Pay+Attention%3F 216 https://www.ncbi.nlm.nih.gov/pubmed/28045107 217 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534876/ 218 https://www.ncbi.nlm.nih.gov/pubmed/31847455 219 https://www.ncbi.nlm.nih.gov/pubmed/24264990 220 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3986062/ 221 https://www.ncbi.nlm.nih.gov/pubmed/6766508 222 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5427073/

andinastateofhomeostasis.223,224,225Inotherwords,ifthereisgutdysbiosis,itmustbetreatedeffectively,whichcouldimprovethesuccessofimmunotherapyinthetreatmentofmalignantcells.

UnravelingtheMysteryofTreatmentTreatActiveInfectionsThescienceiscompellingtounravelthemysteryoftreatment.Ifthereisactiveinflammationandinfectionsthathaveaffectedotherareasofthebody,thesemustbetreatedfirst.AsIhavestressedinthispaper,oneexampleisactiveperiodontaldiseasebecauseithasbecomeasecondsourceforleakageoftoxicelementsintothebloodstreamviathetissuessurroundingtheinfectedteeth.Next,itiscriticaltoavoidwhateverstokestheflamesofinflammationandinfection.Nourishthebodywithprotectiveresourcesbutremovetheirritants.Ifinfectionisactiveinthemouth,thenthemouthmustbetreatedappropriately.Inaddition,whateveriscausingdysbiosisinthegutanddamagetothegutliningmustberemovedandavoided.

UnderstandingPeriodontalDisease

In2016,XueLiandotherspublishedtheirmedicalresearchaboutperiodontaldisease.226Theyusedhealthyhumangumtissuecellsfortheirexperiment.Thesetissuecellswereexposedtolipopolysaccharides(LPS),whicharepresentinthepathogenicbacteriaofperiodontaldisease.TheresultsoftheresearchshowedthatmitochondriainthegumtissuecellsexposedtoLPScreatedexcessreactiveoxygenspecies(ROS).FollowingtheproductionofexcessROS,thegumcellsproducedexcesscytokinesthatcouldleadtoperiodontaldestruction.However,whenthemitochondriaofthesegumtissuecellsweretreatedtoreduceexcessROSproduction,chroniccytokineproductionalsowasreducedeveninthepresenceofLPS.ItappearedthattreatingthemitochondrialdysfunctionstoppedtheprogressionofperiodontaldiseaseregardlessofthepresenceofLPS.

MelissaVosandotherspublishedapaperin2012usingananimalmodel.227Insummary,theydemonstratedthatvitaminK2wasabletorescuedamagedmitochondria,whichhadbeenalteredatthebeginningoftheresearchtorepresentdamagedcellsofParkinson’sDisease.Andin2018,DonikaIvanovaandothersdescribedhowvitaminK2transportsoutoftheliverandthendisseminatesthroughoutthebodytoassistinvariousbiologicalfunctionsincludingthepreventionofmitochondrialdysfunction.228

223 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529202/ 224 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471869/ 225 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6580757/ 226 https://www.ncbi.nlm.nih.gov/pubmed/?term=10.1016%2Fj.yexcr.2016.08.007 227 https://www.ncbi.nlm.nih.gov/pubmed/?term=10.1126%2Fscience.1218632 228 https://www.sciencedirect.com/science/article/pii/S2213231718300934?via%3Dihub

ThethreepreviouspaperssuggestthatvitaminK2couldbeanimportantnutrientindecreasingtheprogressionofperiodontaldiseasebyimprovingmitochondrialfunction.

Repair&RestoretheGutRepairwillconsistofeatingnutrient-dense,anti-inflammatoryfoods.Isuggestedseveralhealthydietsatthebeginningofthischapterandtheimportanceoforganic,wildcaught,andnaturallypasturedanimalproducts.APaleo-typediethasbeenoneofthebestsuitedtoaccomplishoverallhealth.However,theCarnivoreDietmaybesuperiorbecauseitexcludesallantinutrientsfromplants.Italsoincludesthenecessarynutrientsintheanimals’muscle,fat,andorgansforhumanstothrive.Thedisruptioninthehealthybalanceofbacteriainthegutmustberestoredandthegutrepaired.Theprotocoltotreatthegutincludesrepairoftheepitheliallining,supportofthemucouslayer,andgerminationandrestorationofhealthybacteriainthelumenusingprovenprobioticsandprebiotics.Ina2020publishedreview229,theauthorsdescribedhowprebioticsandprobioticsmodulatethegutmircobiomeandconsequentlyhelpwiththepreventionand/ortreatmentofcardiovasculardiseaseassociatedwithmetabolicendotoxemia,whichistheresultofgutdysbiosisandleakygut.Therealsoisevidencethatfecalmicrobiotatransplantscouldassistintherepairofthegutandtreatmentofmanychronicdiseases.230,231

Spore-BasedBacillusProbiotics

Probioticshavebeenshowntoimprovetheclinicalandmicrobialoutcomesfororalandsystemicdiseases.232Inawell-designedstudy,BrianK.McFarlinandotherresearcherspublishedtheirresultsin2017.233Theinvestigatorsselected28participantswhosebloodtestsdemonstratedsignificantendotoxemiaafterconsumingahigh-fat,high-carbohydratemeal.Thisselectgroupofindividualsweredividedintotwogroups.Bothgroupstooktwocapsulesofadailysupplementforfourweeks.Onegrouptookplacebocapsules,andtheothertookcapsulescontainingfivedifferentspore-basedbacillusprobiotics.Attheendofthetrial,participantsateanotherhigh-fat,high-carbohydratemeal.Theirbloodwastestedbeforethemealandthenretestedafterthemeal.Fivehoursafterthemeal,theresultsshowedanaverage42%decreaseofendotoxemiainthegrouptakingtheprobioticcapsules.However,thegrouptakingtheplaceboactuallyhada36%increaseinendotoxemia.Theauthorssuggestedthatthepositiveresultsmightbeimprovedsignificantlyifthespore-basedprobioticsweretakenforseveralmoremonths.

229 https://www.ncbi.nlm.nih.gov/pubmed/31894861 230 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6699279/ 231 https://onlinelibrary.wiley.com/doi/full/10.1002/kjm2.12069 232 https://www.ncbi.nlm.nih.gov/pubmed/31850634 233 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5561432/

Thebenefitsofspore-basedbacillusbacteriaaresignificantforthegut.Onestudylookedat35conventionalprobioticsprimarilycontaininglactobacillussp.andbifidobacteriumsp.WhentheseprobioticsweresubjectedtoasimulatednormalstomachacidofpH1,all35brandswereinactivatedbythestomachacid.AtastomachacidofpH2to3,only18brandsofthe35had50%survival.However,allthespore-basedprobioticssurvivedatastomachacidofpH1.3.234Inanotherstudy,whenconventionalprobioticsweredead,theirmetabolitesstillenteredtheintestinesandprovidedapositivebiologicalresponse.Thisisreferredtoas“metabolicresponsemodifiers”.However,sincethebacteriaweredead,theycouldnotgerminatethemselvesinthegutmicrobiome.235Therefore,theidealprobiotictoingestinordertorepairthegutisaspore-basedbacillusprobiotic.Itwasabletocreatemetaboliteswhichfunctionedasmetabolicresponsemodifiersinthegutaswellasentertheintestinesunscathedtogerminateintonewbeneficialbacteria.236,237,238,239,240

Prebiotics

Prebioticsarenon-digestiblefibersthatfeedthebacteriainthegut.Mostprebioticsonthemarketcanfeedbothbeneficialandharmfulgutbacteria,whichcanexacerbatedigestiveissues.However,oligosaccharidesarespecificfibersthatcanincreasemicrobialdiversityandselectivelyfeedbeneficial,keystonebacterialikeAkkermansiamuciniphila,Faecalibacteriumprausnitzii,andBifidobacteria.

Interestingly,inapaperpublishedin2019,SinghH.etal,studied65humansubjectsranginginagefrom70to82.Theydividedthegroupintohealthyagingandnon-healthyaging.Theynon-healthygroupwasdiagnosedwithoneormoremajordiseases:(1)cancer,(2)acuteorchroniccardiovasculardiseases,(3)acuteorchronicpulmonarydiseases,(4)diabetes,and(5)strokeorneurodegenerativedisorders.TheresearchersobservedthegenusAkkermansiatobesignificantlymoreabundantinthegutmicrobiotaofthehealthyaginggroup.Akkermansiamuciniphilaisacolonicmucin-degradingbacterium,whichhasbeneficialeffectsongastrointestinalhealth.Theinvestigatorswentontostatethatan

234 http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.526.6176&rep=rep1&type=pdf 235 https://www.ncbi.nlm.nih.gov/pubmed/?term=The+probiotic+paradox%3A+Live+and+dead+cells+are+biological+response+modifiers 236 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4669646/ 237 https://www.ncbi.nlm.nih.gov/pubmed/?term=Effects+of+Bacillus+subtilis+on+epithelial+tight+junctions+of+mice+with+inflammatory+bowel+disease 238 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2826289/ 239 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5502041/ 240 https://www.ncbi.nlm.nih.gov/pubmed/?term=Bacillus+clausii+probiotic+strains%3A+antimicrobial+and+immunomodulatory+activities

abundanceofthisgutbacteriumandpossiblyotherscoulddecreasetherisksofnon-healthyaging.241Thereisabundantresearchtoshowthatoligosaccharideswouldbetheidealprobiotictoincludeasasupplementtoassistinrepairingthegut.242,243,244,245Inaddition,asImentionedearlierinthispaper,thegutbacteriahavebeenshowntoproduceasignificantamountofSCFAsfromaminoacidsiffermentablefiberwerenotreadilyavailable.246

MucosalLayer

Themucosalsystemisaveryimportantpartofthehumanimmunesystem.247Itisthemaininterfacebetweenthehumanbodyandtheoutsideworld.Themucosalsystemcontains150timesmoresurfaceareathanskin,whichmakesitoneofthemostimportantimmunebarriers.Thehealthofthemucosadetermineshowthebodyinteractswithantigens;therefore,theintegrityoftheintestinalmucosacandictateoverallimmunefunction.248

Themucosallayercanberepairedandsupportedbyspecificimmunoglobulins,aminoacids,andcitruspolyphenols.

• Immunoglobulins(IgG,IgA,andIgM)willsupporthealthydigestion,neutralizeenvironmentaltoxins,andhelpmaintainhealthygutbarrierfunction.249

• Thekeyaminoacidsthatplayanimportantroleinthehealthymucosallayerinclude:L-proline,L-serine,L-cysteine,andL-threonine.Thesefouraminoacidshavebeenshowntoincreasemucin2productionandstimulatemucinsynthesisinthecolon,resultinginathickerandhealthiermucosalbarrier.250

241 https://www.ncbi.nlm.nih.gov/pubmed/31620923/ 242 https://www.ncbi.nlm.nih.gov/pubmed/?term=Consumption+of+kiwifruit+capsules+increases+Faecalibacterium+prausnitzii+abundance+in+functionally+constipated+individuals%3A+a+randomised+controlled+human+trial 243 https://www.ncbi.nlm.nih.gov/pubmed/?term=Xylooligosaccharide+supplementation+alters+gut+bacteria+in+both+healthy+and+prediabetic+adults%3A+a+pilot+study 244 https://www.ncbi.nlm.nih.gov/pubmed/?term=A+Mixture+of+trans-Galactooligosaccharides+Reduces+Markers+of+Metabolic+Syndrome+and+Modulates+the+Fecal+Microbiota+and+Immune+Function+of+Overweight+Adults 245 https://www.ncbi.nlm.nih.gov/pubmed/?term=Akkermansia+muciniphila-derived+extracellular+vesicles+influence+gut+permeability+through+the+regulation+of+tight+junctions 246 https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-019-0704-8 247 https://www.mdpi.com/2076-2607/7/10/440/htm 248 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5288588/ 249 https://www.ncbi.nlm.nih.gov/pubmed/?term=Survival+and+digestibility+of+orally-administered+immunoglobulin+preparations+containing+IgG+through+the+gastrointestinal+tract+in+humans 250 https://www.ncbi.nlm.nih.gov/pubmed/?term=Specific+Amino+Acids+Increase+Mucin+Synthesis+and+Microbiota+in+Dextran+Sulfate+Sodium%E2%80%93Treated+Rats

• Citruspolyphenolssupportdigestivehealthandhealthygutbarrierfunctionbyincreasingshort-chainfattyacid(SCFA)composition.251

ImportanceoftheMouthTostopperiodontaldiseaseandpreventthisinfectionfromenteringthesystemiccirculation,theinfectionmustbetreatedefficiently.Treatmentmayoftenconsistofadentist,hygienist,orperiodontistremovingirritantsthathavebecomelodgedunderthegumtissuesandinitiatinginflammationandinfection.Removingtheseirritantswillimprovetheoverallsystemicinflammatoryconsequences.252Inmoreadvancedstages,surgicalproceduresmaybenecessarytoarrestthisdisease.Whatevertreatmentisnecessary,anefficientoralhygieneprogramshouldbeinstitutedatafrequencybasedonthepatient’sabilitytotakecareofhisorhermouth.Theindividualalsomusthaveapersonaloralhygieneprotocoltomaintainahealthymouth.

PersonalOralHygieneProtocol

Removingtheamountsofunhealthybacteriafromaroundthetoothisthegoalofflossingandbrushing.Thegoalisnottokillallthebacteriainthemouthsincemuchofthebacteriainthemoutharegoodbacteria.Aneffectivemethodtocleanyourmouthistouse(1)somethingtocleanbetweentheteeth,(2)asofttoothbrushtocleantheothersurfacesoftheteeth,and(3)methodstocleanyourtongue.Performthesemethodstwiceaday–firstthinginthemorningandlastthingatnight.1.CleaningBetweenYourTeeth:Iflossbetweenmyteethusingdentalfloss.Thinkaboutslidingupanddownapole.Thatishowtheflosswrapsaroundthetoothandslidesupanddowntoscrapeawayfoodparticlesthatcouldgetcaughtbetweenthecontactsoftheteeth.Also,Ialwaysuseasmallbrushthatisdesignedtocleanbetweenteethlikeapipecleaner(onebrandiscalledTePeEasyPick®,anotherisGUMSoftPick®).Imaginethesmallbristlesofthistinybrushscrubbingawaytheovergrownbacterialfilmasitispushedinandoutbetweentheteethatthegumline.Thesesmallbrushesarethebestwaytoremoveunhealthyplaquebuildupatthebaseofthetoothandgummargin.2.BrushingYourTeeth:IliketouseanelectrictoothbrushliketheSonicare®ortheOralB/Braun®becauseelectricbrushesaremoreefficient,andIamlazy.Youdonotneedtouseanytoothpastetobrushyourteetheffectively.JustbrushwithfilteredwaterGENTLY,anglingthebristlesintothespacewherethegumsmeettheteethonboththecheeksideandthetonguesideofallteeth.BrushhorizontallybutGENTLY.However,ifyouwanttoothpaste,dipthebristlesinalittlecoconutoil(Ikeepsomewhichstayssolidatroomtemperatureinasmalljarinmybathroom),andthendipthesebristlesintoalittlebakingsoda(Ialsokeepsomeinasmalljarinthebathroom).Hereisanothersubstanceyoucanuseasatoothpaste,butitmaysurpriseyou.Researchhasshownthatrawhoneyiseffectiveatremovingpotentiallyharmfulbacteriaand

251 https://www.ncbi.nlm.nih.gov/pubmed/19566597 252 https://www.ncbi.nlm.nih.gov/pubmed/31849397

preventingtoothdecay,andgumdisease.253,254Honeyhasover200knownbiologicallyactivesubstances255–withmanytobediscoveredinthefuture.Whileallrawhoneyiseffective,mostofthemedicalresearchhasshownthesuperiorityofManukahoneybecauseofsomeofitsunique,biologicallyactivecompounds.256,257Irarelyuseamouthwash,becausedailyuseofanantimicrobialmouthwashwillkillbadbacteriaaswellasgoodbacteria.Killinggoodbacteriadailywillcompromisethehealthinyourmouthandtherestofyourbody.258Ifyouwanttouseamouthwashoccasionally,usesomecoconutoilandswishitaroundforaminuteorso.Then,spititout(calledOilPulling).Ifyouusecoconutoilasamouthwash,besuretospititoutintoanapkinorpapertowelandthrowitinthetrash.Ifyouspitcoconutoilintoyoursink,itcouldclogupthepipes!Bytheway,rawhoneyisalsoanexcellentchoiceforamouthwash.3.BrushingYourTongue:Mostoftheodor-formingbacteriaislocatedonthetopandbackareasofyourtongue,closesttoyourthroat.Aneffectivewaytoremovethisovergrownbacteriaandfoodremnantscausingodoristouseateaspoon.Placetheinvertedteaspoonasfarbackasiscomfortableontheuppersideofyourtongue.Then,gentlyglidetheteaspoonforward,removingtheexcessbacterialfilmandmicroscopicfoodparticles.Repeatthis2-3times,andthenwashofftheteaspoon.

Some“No-Nos”

• Don’tflossunderthegumtissue.Youeasilycouldcutthegumandcreateawound.Thatwoundmightstaysoreandheallikeacleft.Aggressiveflossingunderthegumalsocouldcausegumrecession.

• Awater-pickdevicecanbedangerous.Itcouldforcefooddebrisandbacteriadeeperunderthegumtissuesifusedonamoderate-to-highpressuresetting.Also,theforceofthewaterjetcouldteargumtissuecellsthataretryingtohealinsidethegumspace.

• Ifyoudrinkveryaciddrinks,themineralsofthetoothcouldbecome“softened”untiltheacidinthemouthreturnstonormal.Isuggestthatyoudon’tbrushyourteethrightafterdrinkinganyaciddrink.Researchsuggeststhatyouwaitatleastanhourbeforebrushingafterdrinkinganaciddrink.259Itwouldbeagoodideatorinseyourmouthwithwatertohelpremovetheexcessacidwhileyourmouthregainsitsnormalacidlevel.

FinalThoughts

253 https://www.ncbi.nlm.nih.gov/pubmed/?term=Honey+in+oral+health+and+care%3A+a+mini+review 254 https://www.sciencedirect.com/science/article/pii/S1349007918300975?via%3Dihub 255 https://www.sciencedirect.com/science/article/pii/S0102695X16301843?via%3Dihub 256 https://www.ncbi.nlm.nih.gov/pubmed/28901255 257 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4837971/ 258 https://www.ncbi.nlm.nih.gov/pubmed/?term=10.1007%2Fs11906-017-0725-2 259 https://www.ncbi.nlm.nih.gov/pubmed/?term=10.1111%2Fj.1365-2818.2012.03630.x

Ourbodyisamarvelousandanincrediblycomplexmachine.Itwillrepairandreplaceitstissuesonaregularbasis.However,whenthereareconstantandsite-specificirritants,thebody’sreactionistobecomechronicallyinflamed.Oncetheseedofchronicinflammationisplantedandnurtured,chronicdegenerativediseasesultimatelyresult.Forthemostpart,chronicdiseasesfindtheirorigininagutexhibitingdysbiosis.Ultimatesuccessfultreatmentmusteventuallyincludetherepairandrestorationofahealthygutmicrobiome.Iftherearetoxiccomponentsinthemouth,thesemustberemoved.Inaddition,considerchanginglifestylehabits-startexercisingefficiently,sleeping7-8hourseachnight,andpracticingstressreductiontechniques.Ifsleepiscompromisedbecauseofrestrictionoftheairwayspace,thisiscriticaltohaveevaluatedandproperlytreated.Iflackofnecessarysunlightisaconcern,thenaddressthis.ConsumingmorevitaminD3alongwithvitaminK2wouldbeanintelligentsupplementchoiceintheabsenceofadequatesunlight.Alltheseeffortsandlifestylechangescouldpreventchronicdisease.Theyalsocouldimproveconditionsifyoualreadywerediagnosedwithachronicdisease.Itappearswehaveplentyofevidencethatmuchdiseasebeginsinthegut.Whatyouswallow,breathe,andabsorbthroughyourskincanaffectthegut.Asamatteroffact,anythingthatgetsintoyourbodynomatterhowitgottherewillaffectyourgutandultimatelyeverycellinyourbody.Inaddition,howyousleep,exercise,anddealwithstresscanaffectyourgut.Anunhealthygutputstheentirebodyatrisk.It’syourgut;it’syourhealth;it’syourchoicetomakehealthyadjustments.Justtakechargeofyourhealth.

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