戈登杆菌属丰度降低与肾结石风险增加相关：一项孟德尔随机化分析与动物实验研究

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Abstract： Objective Toinvestigatethecausalrelationshipbetweengutmicrobiotaandkidneystones.MethodsMendelian randomizationanalysis wasconductedbasedondatafromtheMiBioGenconsortiumgutmicrobiotaGWAS（exposurefactors） andtheIUOpenGWASkidneystonedatasetukb-b-8297（outcomevariables）usingtheinversevariance weighted，MR-Egger regression，weightedmedianweightedmode，ndsimplemodemethods.Heterogeneitypleiotropyandleaveeout sensitivityanalyses werealsoperformed.Intheanimalexperiment，12maleSDratswererandomizedintocontrolgroupwith saline treatment and kidney stone model group treated with 1% ethylene glycol and 2% ammonium chloride for 28 consecutivedays.Urine，blood，andintestinalsamplesoftherats werecolectedfortestingthechanges inrenalfunctionand intestinal barier-relatedindicators，andkidneyandcolon pathologieswereexaminedwithhistological stainingand immunohistochemistry.Thechanges indiversityandabundanceofgut microbiota wereanalyzedusing16SrRNAgene sequencing.ResultsMendelianrandomizationanalysisshowed thatdecreased abundancesofLachnospiraceaeNK4A136group （OR=0.9974， 95% CI： 0.9948-0.9999， P=0.0393） and Gordonibacter （OR=0.9987， 95% CI： 0.9974-0.9999， P=0.0403）were associated withanincreasedriskofidneystoneswithoutsignificantheterogeneityororizontalpleiotropyndsensitivityalyes suggestedrobustnessoftheresults.Theratmodelsofkidneystonesexhibitedsignificantrenal functionimpairmentand calciumxalatealpsitioccomadbyeaedeprsssftetialeelaedprotesioed intestinal α -and β -diversityindices.IntestinalGordonibacterabundancewassignificantlyreducedintheratmodels whilethe LachnospiraceaeNK4A136 groupdidnotdifer significantlybetweenthecontrolandmodel groups.Conclusion Decreased Gordonibacter abundanceingut microbiotaisassociated withanincreasedriskof kidneystones.Theprotectiveroleof the LachnospiraceaeNK4A136groupagainstkidneystonesassuggestedbyMendelianrandomizationanalysisfailstobesupported by the experimental evidence and awaits further investigation.

Keywords：gutmicrobiota;kidneystones;Mendelianrandomization;LachnospiraceaeNK4A136group;Gordoibacter

肾结石在全球成年人中的患病率约为 10%[1] 50% 的患者经过临床治疗后会在5～10年复发2。（剩余18467字）