冠心病合并非酒精性脂肪肝患者血清代谢物、肠道菌群与预后的关系

冠心病合并非酒精性脂肪肝患者血清代谢物、肠道菌群与预后的关系摘要：本研究旨在探讨冠心病合并非酒精性脂肪肝患者血清代谢物、肠道菌群与预后的关系。选取2017年1月至2019年12月在我院就诊并确诊的冠心病合并非酒精性脂肪肝患者90例，通过酸性聚丙烯酰胺凝胶电泳技术分析患者血清代谢物的谱图，同时采集粪便样本进行16SrRNA基因测序分析肠道菌群。以患者的住院时间、死亡率、再次住院情况等为指标进行预后评估。结果显示，冠心病合并非酒精性脂肪肝患者的血清代谢物和肠道菌群与预后有着密切的关系。其中，血清代谢物的变化与患者的再次住院情况呈正相关，而肠道菌群则与患者的死亡率和住院时间呈负相关。结论：本研究为深入探究冠心病合并非酒精性脂肪肝患者的代谢与肠道菌群在预后中的作用提供了新的研究思路和实验依据。

关键词：冠心病；非酒精性脂肪肝；预后；血清代谢物；肠道菌群

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