REVIEWOpenAccessGutmicrobiotaandcardiovasculardisease:opportunitiesandchallengesNeginKazemian1,MortezaMahmoudi2*,FrankHalperin3,JosephC.Wu4,5,6andSepidehPakpour1*AbstractCoronaryarterydisease(CAD)isthemostcommonhealthproblemworldwideandremainstheleadingcauseofmorbidityandmortality.Overthepastdecade,ithasbecomeclearthattheinhabitantsofourgut,thegutmicrobiota,playavitalroleinhumanmetabolism,immunity,andreactionstodiseases,includingCAD.AlthoughcorrelationshavebeenshownbetweenCADandthegutmicrobiota,demonstrationofpotentialcausalrelationshipsismuchmorecomplexandchallenging.Inthisreview,wewilldiscussthepotentialdirectandindirectcausalrootsbetweengutmicrobiotaandCADdevelopmentviamicrobialmetabolitesandinteractionwiththeimmunesystem.UncoveringthecausalrelationshipofgutmicrobiotaandCADdevelopmentcanleadtonovelmicrobiome-basedpreventativeandtherapeuticinterventions.However,aninterdisciplinaryapproachisrequiredtoshedlightongutbacterial-mediatedmechanisms(e.g.,usingadvancednanomedicinetechnologiesandincorporationofdemographicfactorssuchasage,sex,andethnicity)toenableefficaciousandhigh-precisionpreventativeandtherapeuticstrategiesforCAD.Keypoints�ThecausalrelationshipbetweengutmicrobiotaandCADdevelopmenthasyettobeconfirmed.�ItisimperativetounderstandthepotentialdirectandindirectcausalrootsbetweengutmicrobiotaandCADdevelopmentviamicrobialmetabolitesandinteractionwiththeimmunesystem.�Dynamicelementsincludingourdietanddemographicfactorssuchasage,sex,andethnicitycanalsoaffectourgutmicrobiotaandCADdevelopmentandcomplicatethismatter.�InterdisciplinaryapproachesarerequiredtoshedlightonthefactorsinvolvedinthemodulationofgutmicrobiotaanditsassociationwithCADdevelopment.�Elucidatingthesystem-levelmultifacetedweboffac-torsinvolvedinmicrobiome-mediatedmechanismsandhumanhealthanddiseasecanguidenovelpre-ventativeandtherapeuticinterventionsforCAD.IntroductionHighserumcholesterol(hypercholesterolemia)isawell-documentedriskfactorforthemostprevalentformofcardiovasculardisease(CVD)knownasc...
