GutMicrobiotainCardiovascularHealthandDiseaseW.H.WilsonTang,MD1,2,3,TakeshiKitai,MD,PhD2,andStanleyLHazen,MD,PhD1,21DepartmentofCellularandMolecularMedicine,LernerResearchInstitute,ClevelandClinic,ClevelandOH441952DepartmentofCardiovascularMedicine,HeartandVascularInstitute,ClevelandClinic,ClevelandOH441953CenterforClinicalGenomics,ClevelandClinic,ClevelandOH44195AbstractSignificantinterestinrecentyearshasfocusedongutmicrobiota-hostinteractionbecauseaccumulatingevidencehasrevealedthatintestinalmicrobiotaplayanimportantroleinhumanhealthanddisease,includingcardiovasculardiseases.Changesinthecompositionofgutmicrobiotaassociatedwithdisease,referredtoasdysbiosis,havebeenlinkedtopathologiessuchasatherosclerosis,hypertension,heartfailure,chronickidneydisease,obesityandtype2diabetesmellitus.Inadditiontoalterationsingutmicrobiotacomposition,themetabolicpotentialofgutmicrobiotahasbeenidentifiedasacontributingfactorinthedevelopmentofdiseases.Recentstudiesrevealedthatgutmicrobiotacanelicitavarietyofeffectsonthehost.Indeed,thegutmicrobiomefunctionslikeanendocrineorgan,generatingbioactivemetabolites,thatcanimpacthostphysiology.Microbiotainteractwiththehostthroughanumberofpathways,includingthetrimethylamine(TMA)/trimethylamineN-oxide(TMAO)pathway,short-chainfattyacidspathway,andprimaryandsecondarybileacidspathways.Inadditiontothese“metabolismdependent”pathways,metabolismindependentprocessesaresuggestedtoalsopotentiallycontributetoCVDpathogenesis.Forexample,heartfailureassociatedsplanchniccirculationcongestion,bowelwalledemaandimpairedintestinalbarrierfunctionarethoughttoresultinbacterialtranslocation,thepresenceofbacterialproductsinthesystemiccirculationandheightenedinflammatorystate.Thesearebelievedtoalsocontributetofurtherprogressionofheartfailureandatherosclerosis.Thepurposeofthecurrentreviewistohighlightthecomplexinterplaybetweenmicrobiota,theirmetabolitesandthedevelopmentandprogressionofcardiovasculardiseases.Wewillalsodiscusstherolesofgutmicrobiotainnormalphysiologyandt...
