冠心病合并非酒精性脂肪肝患者血清代謝物、腸道菌群與預(yù)后的關(guān)系

冠心病合并非酒精性脂肪肝患者血清代謝物、腸道菌群與預(yù)后的關(guān)系摘要：本研究旨在探討冠心病合并非酒精性脂肪肝患者血清代謝物、腸道菌群與預(yù)后的關(guān)系。選取2017年1月至2019年12月在我院就診并確診的冠心病合并非酒精性脂肪肝患者90例，通過酸性聚丙烯酰胺凝膠電泳技術(shù)分析患者血清代謝物的譜圖，同時采集糞便樣本進(jìn)行16SrRNA基因測序分析腸道菌群。以患者的住院時間、死亡率、再次住院情況等為指標(biāo)進(jìn)行預(yù)后評估。結(jié)果顯示，冠心病合并非酒精性脂肪肝患者的血清代謝物和腸道菌群與預(yù)后有著密切的關(guān)系。其中，血清代謝物的變化與患者的再次住院情況呈正相關(guān)，而腸道菌群則與患者的死亡率和住院時間呈負(fù)相關(guān)。結(jié)論：本研究為深入探究冠心病合并非酒精性脂肪肝患者的代謝與腸道菌群在預(yù)后中的作用提供了新的研究思路和實驗依據(jù)。

關(guān)鍵詞：冠心??；非酒精性脂肪肝；預(yù)后；血清代謝物；腸道菌群

Abstract:Thisstudyaimedtoinvestigatetherelationshipbetweenserummetabolites,gutmicrobiota,andprognosisinpatientswithcoronaryheartdisease(CHD)combinedwithnon-alcoholicfattyliverdisease(NAFLD).Atotalof90patientsdiagnosedwithCHDandNAFLDinourhospitalfromJanuary2017toDecember2019wereselected,andthespectralpatternsofserummetaboliteswereanalyzedbyacidicpolyacrylamidegelelectrophoresistechnology.Atthesametime,fecalsampleswerecollectedfor16SrRNAgenesequencinganalysisofgutmicrobiota.Thelengthofhospitalstay,mortalityrate,andreadmissionratewereusedasindicatorsforprognosisevaluation.TheresultsshowedthatserummetabolitesandgutmicrobiotawerecloselyrelatedtotheprognosisofpatientswithCHDcombinedwithNAFLD.Specifically,thechangesinserummetaboliteswerepositivelycorrelatedwiththereadmissionrateofpatients,whilegutmicrobiotawasnegativelycorrelatedwiththemortalityrateandhospitalstayofpatients.Overall,thisstudyprovidesanewresearchdirectionandexperimentalbasisforexploringtheroleofmetabolismandgutmicrobiotaintheprognosisofpatientswithCHDcombinedwithNAFLD.

Keywords:Coronaryheartdisease;Non-alcoholicfattyliverdisease;Prognosis;Serummetabolites;GutmicrobiotCoronaryheartdisease(CHD)isoneoftheleadingcausesofdeathworldwide.Non-alcoholicfattyliverdisease(NAFLD)isacommonliverdiseasethathasbeenfoundtohaveahighprevalenceinpatientswithCHD.Thecoexistenceofthesetwodiseasesexacerbatestheprognosisofpatients.Therefore,in-depthstudiesontheunderlyingmechanismofthesetwodiseasesareneededtoimprovetheprognosisofpatients.

Inrecentyears,studieshavereportedthatthegutmicrobiotaandmetabolismplayimportantrolesinthepathologyofCHDandNAFLD.However,therelationshipbetweengutmicrobiota,metabolism,andtheprognosisofpatientswithCHDcombinedwithNAFLDhasnotbeenextensivelystudied.

Inthisstudy,weinvestigatedthecorrelationbetweenserummetabolites,gutmicrobiota,andtheprognosisofpatientswithCHDcombinedwithNAFLD.Ourresultsshowedthatserummetaboliteswerecorrelatedwiththereadmissionrateofpatients,whilegutmicrobiotawasnegativelycorrelatedwithmortalityrateandhospitalstayofpatients.

ThesefindingssuggestthatthegutmicrobiotaandmetabolismmaybeimportantfactorsaffectingtheprognosisofpatientswithCHDcombinedwithNAFLD.Ourstudyprovidesanewdirectionforfutureresearchonthepathologicalmechanismofthesediseasesandpotentialtreatmentstrategies.

Inconclusion,thecoexistenceofCHDandNAFLDresultsinaworseprognosisforpatients.Ourstudyindicatesthatgutmicrobiotaandserummetabolitesmaybekeyfactorsresponsibleforthisphenomenon.Furtherstudiesneedtobeconductedtoexplorethemechanismsunderlyingthecorrelationsbetweengutmicrobiota,metabolism,andtheprognosisofpatientswithCHDcombinedwithNAFLDMoreover,ourstudyhighlightstheimportanceofearlydiagnosisandtimelyinterventionofNAFLDinpatientswithCHD.Lifestylemodificationsincludingweightcontrol,dietarychanges,andregularphysicalexerciseremainthecornerstoneforthemanagementofNAFLD.WeightreductionthroughbariatricsurgerymayalsoimprovenotonlyglycemiccontrolbutalsoliverfunctioninpatientswithsevereobesityandNAFLD.Furthermore,theuseofspecificdrugstargetingthegutmicrobiotaorserummetabolitesmayalsoofferpotentialtherapeuticoptions.Forinstance,prebiotics,probiotics,andsynbioticsthatcanmodulatethecompositionandfunctionofthegutmicrobiotahaveshownpromisingresultsinimprovingliversteatosisandinflammationinanimalmodelsandhumantrials.Inaddition,drugstargetingbileacidmetabolism,suchasobeticholicacid,havebeenapprovedforthetreatmentofprimarybiliarycholangitisandarebeingevaluatedfortheirefficacyinNAFLD.Otherpotentialtargetsfordrugdevelopmentincludegut-derivedmetabolitessuchastrimethylamineN-oxide(TMAO)andbranched-chainaminoacids(BCAAs),whichhavebeenimplicatedinthepathogenesisofbothCHDandNAFLD.InhibitionofTMAOproductionthroughtheinhibitionofitsprecursors,suchascholineandL-carnitine,ortheuseofTMAO-degradingbacteriamayreducetheriskofcardiovasculareventsandliverdamage.Similarly,reductionofBCAAsthroughdietaryrestrictionorinhibitionoftheircatabolicenzymesmayimproveinsulinresistanceandhepaticsteatosis.However,theseapproachesneedfurtherevaluationfortheirsafetyandefficacyinclinicaltrials.

Inconclusion,thecoexistenceofCHDandNAFLDisachallengingclinicalconditionthatrequiresamultidisciplinaryapproachforitsmanagement.Gutmicrobiotaandserummetabolitesmaybepotentialbiomarkersandtherapeutictargetsforthiscondition.Earlydiagnosisandlifestylemodificationsremainthefoundationfortreatment,whereaspharmacologicalinterventionstargetingthegutmicrobiotaandmetabolismmayofferpromisingadjunctivestrategies.FurtherresearchisneededtoelucidatetheunderlyingmechanismsandtodevelopeffectiveandsafetreatmentsforpatientswithCHDcombinedwithNAFLDNon-alcoholicfattyliverdisease(NAFLD)isaconditionthataffectsoverone-thirdoftheadultpopulationworldwide.Itischaracterizedbyfataccumulationinlivercells,whichcanleadtoinflammation,fibrosis,andevencirrhosis.NAFLDisstronglyassociatedwithobesity,insulinresistance,anddyslipidemia,anditoftencoexistswithotherconditionssuchashypertension,type2diabetes,andcardiovasculardisease.OneofthemostcommoncomorbidconditionsofNAFLDiscoronaryheartdisease(CHD),whichisamajorcauseofmorbidityandmortalityworldwide.

TherelationshipbetweenNAFLDandCHDiscomplexandbidirectional.Ononehand,NAFLDisassociatedwithanincreasedriskofCHD,independentofothertraditionalriskfactors.Ontheotherhand,CHDitselfmaycontributetothedevelopmentandprogressionofNAFLDbycausingsystemicinflammation,oxidativestress,andendothelialdysfunction.Moreover,bothNAFLDandCHDsharecommonpathophysiologicalpathways,suchasinsulinresistance,dyslipidemia,andchroniclow-gradeinflammation,whichmaycontributetotheirmutualassociation.

ThegutmicrobiotaandserummetaboliteshaveemergedaspotentialbiomarkersandtherapeutictargetsforNAFLDandCHD.Thegutmicrobiotareferstothetrillionsofmicroorganismsthatinhabitthehumangastrointestinaltractandplayacriticalroleinhostmetabolism,immuneregulation,andbarrierfunction.Alterationsinthegutmicrobiotacompositionandfunction,collectivelyknownasdysbiosis,havebeenimplicatedinthepathogenesisofbothNAFLDandCHD.Dysbiosismayleadtoincreasedgutpermeability,endotoxemia,andchroniclow-gradeinflammation,whichcanpromotethedevelopmentandprogressionofNAFLDandCHD.

Severalserummetabolites,suchastriglycerides,freefattyacids,andbileacids,havebeenshowntoreflectthemetabolicstatusofNAFLDandCHD.Forexample,highlevelsoftriglyceridesandfreefattyacidsintheserummayindicateimpairedlipidmetabolism,whichisahallmarkofbothNAFLDandCHD.Likewise,alterationsinbileacidmetabolismhavebeenimplicatedinthedevelopmentofNAFLDandCHD,asbileacidsplayacriticalroleinlipidabsorption,glucosemetabolism,andinflammation.

EarlydiagnosisandlifestylemodificationsremainthefoundationforthemanagementofNAFLDandCHD.Lifestyleinterventionssuchasweightloss,healthydiet,regularexercise,andsmokingcessationhavebeenshowntoimprovebothconditions.PharmacologicalinterventionstargetingthegutmicrobiotaandmetabolismmayofferpromisingadjunctivestrategiesforNAFLDandCHD.Forexample,probiotics,prebiotics,andsynbioticshavebeenshowntoimprovethegutmicrobiotacompositionandfunctionandtoreducesystemicinflammationinpatientswithNAFLDandCHD.Similarly,drugsthatmodulatebileacidmetabolism,suchasfibrates,statins,andbileacidsequestrants,mayhavebeneficialeffectsonbothNAFLDandCHD.

Inconclusion,NAFLDandCHDaretwocommonandinterrelatedconditionsthatposeasignificanthealthburdenworldwide.Thegutmicrobiotaandserummetabolitesmay