The Human Microbiome: the Undiscovered Country
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UpdateUpdate inin GI:GI: WhatWhat’’ss NewNew andand UsefulUseful WalterWalter J.J. Coyle,Coyle, MD,MD, FACP,FACGFACP,FACG OctoberOctober 20122012 DisclosuresDisclosures II havehave nono disclosuresdisclosures relatedrelated toto thisthis talktalk Specifically,Specifically, II havehave nono interestsinterests inin anyany probioticprobiotic oror prepre--bioticbiotic brandsbrands MovementMovement ofof thethe TalkTalk EosinophilicEosinophilic esophagitis:esophagitis: WhatWhat isis itit andand howhow dodo II treattreat it?it? GERD:GERD: WhatWhat’’ss New?New? CeliacCeliac Sprue:Sprue: TheThe epidemicepidemic CRCCRC screening:screening: FollowFollow thethe guidelinesguidelines WhatWhat’’ss new?new? MovementMovement ofof thethe TalkTalk PartPart IIII StoolStool Transplants:Transplants: TheThe NewNew RageRage RosaceaRosacea andand SIBO:SIBO: NewNew evidenceevidence ChronicChronic nausea:nausea: aa newnew linklink TheThe HumanHuman Microbiome:Microbiome: HotHot topictopic ProPro andand PrePre biotics:biotics: aa rationalrational approachapproach C.C. difficiledifficile :: ItIt willwill notnot gogo away!away! ConclusionsConclusions QuestionQuestion NumberNumber 11 2727 yearyear oldold malemale A. PepticPeptic stricturestricture presentspresents withwith intermittentintermittent solidsolid foodfood B. SchatzkiSchatzki ’’ss ringring dysphagiadysphagia forfor years.years. HeHe C. EosinophilicEosinophilic esophagitisesophagitis hashas hadhad 22 foodfood D. AdenocarcinomaAdenocarcinoma ofof thethe impactions.impactions. HeHe hadhad distaldistal esophagusesophagus childhoodchildhood asthma.asthma. E. AchalasiaAchalasia The most likely The most likely diagnosisdiagnosis is?is? EosinophilicEosinophilic EsophagitisEsophagitis Common,Common, maymay bebe increasingincreasing HigherHigher inin males,males, youngeryounger ptspts withwith h/oh/o atopyatopy StrongStrong associationassociation withwith foodfood andand aeroallergensaeroallergens THETHE ALLERGICALLERGIC ESOPHAGUSESOPHAGUS Adults:Adults: presentpresent withwith dysphagia,dysphagia, atypicalatypical GERDGERD symptoms:symptoms: UsuallyUsually havehave yearsyears ofof symptomssymptoms Children:Children: FailureFailure toto thrive,thrive, nauseanausea oror vomiting.vomiting. EosinophilicEosinophilic EsophagitisEsophagitis LinearLinear FurrowsFurrows RingsRings Diagnosis:Diagnosis: BiopsyBiopsy atat endoscopyendoscopy EosinophilicEosinophilic EsophagitisEsophagitis Eos.Eos. AbscessesAbscesses Long,Long, oftenoften complexcomplex stricturesstrictures CarefulCareful dilationdilation EosinophilicEosinophilic EsophagitisEsophagitis MucosalMucosal teartear afterafter scopescope passagepassage TryTry medicalmedical treatmenttreatment firstfirst EosinophilicEosinophilic Esophagitis:Esophagitis: TreatmentTreatment PPIsPPIs havehave shownshown efficacyefficacy inin upup toto 50%50% ofof ptspts TopicalTopical steroidssteroids usefuluseful butbut recentrecent PC/RandPC/Rand studiesstudies havehave shownshown lessless efficacyefficacy thenthen openopen labellabel studiesstudies FluticosoneFluticosone oror budesonide:budesonide: SwallowedSwallowed (not(not inhaled)inhaled) AllergyAllergy consultation:consultation: MayMay bebe helpfulhelpful inin findingfinding foodfood oror aeroallergenaeroallergen thatthat isis mainmain culpritculprit Am J Gastroenterol 2010; 105:747–756 GERD:GERD: WhatWhat’’ss HotHot VisceralVisceral AdiposityAdiposity IncreasesIncreases thethe RiskRisk ofof GERDGERD Subcutaneous adiposity Visceral adiposity Courtesy of Brian Jacobson ObesityObesity--SeparationSeparation ofof thethe LESLES andand DiaphragmaticDiaphragmatic CrusCrus HRM Inspiration LES Crural separation Diaphragm Visceral Adiposity Intragastric Intragastric Pressure Pressure Normal Obese Pandolfino JE, et al. Gastroenterology 2006; 639-349 GERDGERD andand BMI:BMI: WomenWomen An increase in BMI of 3.5 was associated with increased risk of frequent GERD symptoms, even in women with normal baseline weight 4 P<0.001 3.5 Multivariate 3 odds in women 2.5 with at least 2 weekly GERD Odds Ratio 1.5 symptoms 1 (n=2306) or no 0.5 symptoms 0 (n=3904) <20 20 22 25 27 30 ≥35 N Engl J Med 2006;354:2340-2348. ObesityObesity asas aa RiskRisk Factor:Factor: BarrettBarrett’’ss EsophagusEsophagus Risk of Barrett’s Esophagus in Obesity with GERD Symptoms Obesity Odds Ratio 95% CI With GERD Symptoms 34.4 6.3-188.0 Without GERD Symptoms 0.7 0.2-2.4 n = 167 with histologically confirmed Barrett’s esophagus Smith KJ, et al. Cancer Epidemiol Biomarkers Prev. 2005;14:2481-2486. n = 2602 Hvid-Jensen et al., NEJM 2011;365(15):1375-1385 Lower Incidence of EAC with Larger Studies Wani et al Clin Gastroenterol Hep. 2011; 9:200-220 GERDGERD PPIsPPIs areare nono longerlonger viewedviewed asas innocuousinnocuous medsmeds MalabsorptionMalabsorption ofof nutrientsnutrients Iron, calcium, Vitamin B12B12 IncreaseIncrease riskrisk forfor fracturesfractures IncreaseIncrease riskrisk forfor infectionsinfections includingincluding ClostridiumClostridium difficiledifficile InteractionInteraction withwith clopidogrelclopidogrel (less(less anan issueissue now)now) PPIPPI useuse andand HipHip fracturefracture CaseCase--controlcontrol studystudy ofof patientspatients olderolder thanthan 5050 yearsyears inin aa largelarge UKUK databasedatabase PPI users had a 4 /1000 risk for hip fx vs 1.8 /1000 in non- users of acid related meds Absolute risk still low SevenSeven casecase controlcontrol oror cohortcohort trialstrials havehave shownshown aa smallsmall absoluteabsolute increasedincreased riskrisk ofof fracturesfractures RecentRecent metameta--analysisanalysis (DDW(DDW absabs only)only) showedshowed aa slightslight increaseincrease inin hiphip fxfx withwith PPIPPI therapytherapy JAMA 2006;296:2947-29 Calcif Tissue Int. 2008;83:251-259 LongLong termterm PPIPPI useuse AGAAGA nownow recommendsrecommends CalciumCalcium // VitVit DD inin longlong termterm usersusers atat riskrisk forfor osteoporosisosteoporosis NoNo guidelinesguidelines forfor monitoringmonitoring B12B12 oror ironiron BeBe aware,aware, checkcheck whenwhen clinicallyclinically indicatedindicated BeBe awareaware ofof medsmeds thatthat absorbabsorb betterbetter withwith acidacid Digoxin,Digoxin, amoxicillin,amoxicillin, ketoconazole,ketoconazole, iron,iron, calciumcalcium OrganicOrganic (heme(heme derived)derived) ironiron nownow availableavailable PPIsPPIs andand InfectionsInfections StudiesStudies havehave linkedlinked acidacid suppresionsuppresion medsmeds includingincluding PPIsPPIs withwith C.C. difficiledifficile infectioninfection HigherHigher recurrencerecurrence ofof CC diffdiff ifif onon PPIPPI atat timetime ofof RxRx MayMay increaseincrease riskrisk forfor hospitalhospital acquiredacquired pneumoniapneumonia Am J Gastro 2007;102:2047-56 CMAJ 2004;171:33-38 JAMA. 2004;292:1955-60 Ann Intern Med. 2008;149:391-98 Arch Intern Med 2010;170:772-8 Arch Intern Med. 2010;170(9):772-778 42% more likely to recur if on PPIs PPIs:PPIs: WaltWalt’’ss RecsRecs RightRight drug,drug, rightright disease,disease, rightright patientpatient IfIf youryour patientpatient needsneeds thethe PPIPPI forfor PUD,PUD, GIGI bleeding,bleeding, BarrettBarrett ’’ss esophagus,esophagus, thenthen useuse thethe PPIPPI Lowest dose that works Use Calcium and Vit D in long term users IfIf itit isis symptomaticsymptomatic GERDGERD only,only, otherother optionsoptions LifestyleLifestyle changes,changes, H2H2 blockers,blockers, antacidsantacids InformedInformed consentconsent toto patientpatient untiluntil finalfinal datadata NB.NB. MoreMore GIGI bleedingbleeding inin CogentCogent studystudy inin nonnon--PPIPPI usersusers CeliacCeliac Disease:Disease: WhatWhat’’ss New!New! CommonCommon gene:gene: DQ2DQ2 andand DQ8:DQ8: UpUp toto 25%25% ONLYONLY predisposespredisposes oneone toto CeliacCeliac ActualActual diseasedisease inin 1%1% inin US:US: IcebergIceberg analogyanalogy GlutenGluten enteropathyenteropathy VSVS GlutenGluten intoleranceintolerance GlutenGluten avoidanceavoidance isis inin vogue!!!vogue!!! Diagnosis:Diagnosis: GoldGold standardstandard remainsremains SBSB biopsybiopsy Serology:Serology: TissueTissue TransglutaminaseTransglutaminase andand EndomysialEndomysial antibodyantibody excellentexcellent sens/specificitysens/specificity ALWAYSALWAYS checkcheck serumserum IgAIgA (IgA(IgA deficiency)deficiency) CeliacCeliac BurdenBurden VaryingVarying FormsForms ofof CeliacCeliac DiseaseDisease • ClassicalClassical celiacceliac diseasedisease ofof childhoodchildhood • LateLate onset,onset, nonnon--specificspecific GIGI symptomssymptoms • DermatitisDermatitis herpetiformisherpetiformis • ExtraExtra --intestinalintestinal presentationspresentations (many)(many) • AssociatedAssociated conditionsconditions (many)(many) • SilentSilent oror asymptomaticasymptomatic celiacceliac diseasedisease (relatives)(relatives) • LatentLatent oror potentialpotential celiacceliac diseasedisease DermatitisDermatitis HerpetiformisHerpetiformis • Pruritic papulovesicular lesions IgA deposits at dermal-epidermal junction • Almost all have abnormal intestinal biopsies Few have GI symptoms • Treatment directed against skin doesn’t help gut lesions (e.g., dapsone) • Gluten free diet helps both gut and skin AssociatedAssociated AutoimmuneAutoimmune ConditionsConditions • DiabetesDiabetes mellitusmellitus -- TypeType II ~~ 33 toto 88 %% havehave celiacceliac diseasedisease • AutoimmuneAutoimmune thyroidthyroid diseasedisease (~5%) • AddisonAddison ’’ss diseasedisease • AlopeciaAlopecia areataareata