When your heart depends on your gut feelings.

Editorial

When

your

heart

depends

on

your

gut

feelings

Cuando

el

corazo´n

depende

del

tracto

digestivo

Lucia

Musumeci,

Ce´cile

Oury,

and

Patrizio

Lancellotti

*

a_{DepartmentofCardiologyandCardiovascularSurgery,UniversityofLie`geHospital,GIGACardiovascularSciences,CHUSartTilman,Lie`ge,Belgium} b_{GruppoVillaMariaCareandResearch,MariaCeciliaHospital,Cotignola,andAntheaHospital,Bari,Italy}

The epidemiology, microbiology, and diagnosis of infective endocarditis(IE)haschangedrapidlyoverthelast50years.The InternationalCollaborationonEndocarditis(ICE)study1_reported

that the most prevalent causes of IE were degenerative valve diseaseand thepresenceofprostheticvalves(inthe1960sand 1970s themain causeswere rheumaticlesions). Moreover, the very recent EURO-ENDO observationalstudy hashighlighted a changeinthemicrobiologyof IE—themostprevalent causative microorganismsarestaphylococci(44%),followedbyenterococci (15.8%), oral streptococci (12.3%), and Streptococcus gallolyticus (6.6%)—andenterococciarenolongerthethirdcauseofIE,asthey wereatthetime oftheICEstudy,andhavebecomethesecond cause.Thisisprobablyduetotheincreasingproportionofolder patientswithcomorbiditiesaffectedbyIE,whichalsomakesIEa diseasewithpoorprognosis.2

Gutpermeabilityandinflammation,beingmoreprevalentin theolderpopulation,couldexplaingutbacteria‘‘leakage’’inthe systemiccirculation,potentiallycausingnotonlycardiovascular butalsoautoimmunediseases.3_{Enterococciarethemostabundant}

bacteria in the human gastrointestinal tract (small and large intestine), representing 1% of the human fecal flora, with Enterococcusfaecalis and Enterococcus faecium beingthe2 _main

species of the enterococcus genus. In healthy individuals, enterococciplayacommensal/probioticrolebut,inelderlypeople, whoaremorefrequentlyaffectedbydysbiosis(animbalanceinthe communityofhealthyhumangutmicrobiota),bacteriacancross themucosaofthegutandenterthecirculation.Oneofthemany ways the microbiota maintain intestinal homeostasis is by stimulatinggobletcellsecretionofmucin,whichisathicklayer protecting the colonic epithelium from intestinal microbes. Wheneverthiscommensalroleisnotachieved,bacteriacanenter thecirculation and colonize otherareas of the body and form biofilms.4_{Chronicdysbiosisassociatedwithotherfactors,suchas}

geneticsanddiet-derivedchemical irritants,caninducechronic colonicinflammationandleadtocolorectaldiseasesandcolorectal neoplasia(CRN),whichcanprogresstocolorectalcancer(CRC).5

Enterococciarenottheonlybacteriaabletocrossthemucosaof thecolon,S.gallolyticus,whichis,however,notpresentinmost humangut(2.5%-15%ofhealthyhumans),alsohasthisproperty. S. gallolyticusbacteremia hasbeen extensively studiedand the mechanismoftranslocationanddisseminationiswellunderstood. Translocationhappensthroughsurface-exposedadhesinsallowing

adhesiontohostcells,whereasdisseminationinvolvesthepilus (Pil3expression),whichbindstoplasmafibrinogen.Onceinthe blood stream, Pil1 expressionis responsible for thebinding to collagen I (present on the surfaces of damaged heart valves), achieving heart colonization.6 _{As long ago as the 1970s,}

S. gallolyticusbacteremiawasfoundtobeassociated withboth CRNandIE.7

Incontrast,themechanismofE.faecalisbacteremiaislesswell known. Although the main portal of entry of E. faecalis is the genitourinarytract,ithasbeenshownthatE.faecalisovergrowth can stimulate reactive oxygen species production and induce genomic instability in colonic cells, favoring lesions of the intestinal mucosa and translocation of E. faecalis in the blood circulation8_(figure1).

Supportingthehypothesisofthegastroenterictractasaportal of entryof E.faecalisbacteremia,a studypublishedin 2017by Perica`setal.exploredtherelationshipbetweenE.faecalisIE(EFIE) and CRN. Theseauthors examined the prevalence of colorectal neoplasmsin EFIEpatientswhosepresumed sourceofinfection couldnotbedeterminedandfoundthat50.8% hadCRN. Inthe groupofpatientswithanidentifiedportalofentryoftheinfection, only 6 patients underwent colonoscopy and 1 of them was diagnosed withCRN (16.7%);thereforeno conclusionscouldbe drawnforthisgroup.9

In an article by Escola`-Verge´ et al.,10 _{recently published in}

RevistaEspan˜oladeCardiologı´a,theauthorsaimedtodetermine theprevalenceofcolorectaldiseaseinEFIEpatients,irrespectiveof thehypothesizedsourceofinfection.Therationalebehindtheir study was based on the fact that 5% of patients with IE (all etiologies) would experience recurrent infection with a higher mortalityrisk,thereasonbeingapotentialundiagnosedcolorectal disease (portalof entryof bacteria into thecirculation). Ifthis hypothesis is correct, performing a colonoscopy, which couldidentifyandtreattheupstreamcauseoftheendocarditis, woulddecreasetheriskofrecurrence.Intheirstudy,theauthors included all consecutive episodes (n = 103) with EFIE seen in 4referralcenters(3centersinSpainand1inItaly).Patientswere classifiedbasedonthepresumedsourceofinfectionintopatients with‘‘unknownportalofentry’’andpatientswith‘‘knownportalof entry’’.Only70EFIEpatientsunderwentcolonoscopy(6months before orafter theEFIEdiagnosis):patients withan‘‘unknown portal of entry’’ were more numerous than those with an ‘‘knownportalofentry’’(64%vs36%).

Comparison of demographic and clinical characteristics be-tweenthe2groupsrevealedthathealthcare-associatedinfections weremoreprevalentinpatientswitha‘‘knownportalofentry’’ than in those withan‘‘unknown portal of entry’’(83% vs 29%,

RevEspCardiol.2020;xx(x):xxx–xxx

SEERELATEDCONTENT:

https://doi.org/10.1016/j.rec.2019.07.007

* Correspondingauthor:DepartmentofCardiology,UniversityofLie`geHospital, DomaineUniversitaireduSartTilman,B35,4000Lie`ge,Belgium.

E-mailaddress:plancellotti@chuliege.be(P.Lancellotti).

GModel

REC-10245;No.ofPages3

Please cite this article in press as: Musumeci L, et al. When your heart depends on your gut feelings. Rev Esp Cardiol. 2020.

https://doi.org/10.1016/j.rec.2020.03.006

https://doi.org/10.1016/j.rec.2020.03.006