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张青,陈国伟,苏镜旭,胡晓璇,卢富华,刘旭生,张蕾.基于肠道菌群和代谢组学探索糖尿病肾病中医湿证生物学特征[J].,2023,43(7):791-800
基于肠道菌群和代谢组学探索糖尿病肾病中医湿证生物学特征
Biological Characteristics of Diabetic Nephropathy with Dampness Syndrome Based on Intestinal Flora and Metabonomics
  
DOI:10. 7661/j. cjim. 20230531.084
中文关键词:  糖尿病肾脏病  湿热证  水湿证  湿浊证  肠道微生物  代谢组学  中医
英文关键词:diabetic kidney diseases  dampheat syndrome  water dampness syndrome  dampturbidity syndrome  intestinal microecology  metabolomics  Chinese medicine
基金项目:省部共建中医湿证国家重点实验室专项(No.SZ2020ZZ22,No.SZ2021ZZ16,No.SZ2021ZZ43);广东省中医证候临床研究重点实验室专项(No.ZH2020KF02);广州市科学技术局重点研发计划(No.202206010076)
Author NameAffiliation
张青,陈国伟,苏镜旭,胡晓璇,卢富华,刘旭生,张蕾 1.省部共建中医湿证国家重点实验室广州中医药大学第二附属医院(广州 510120)
2.广州中医药大学第二临床医学院(广州 510405)
3.广州中医药大学第二附属医院肾内科(广州 510120)
4.广东省中医证候临床研究重点实验室(广州 510120) 
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中文摘要:
      目的 探讨糖尿病肾脏病(DKD)中医湿证的差异肠道菌群、潜在生物标志物及代谢通路。方法 选择2017年1月—2019年12月储存在广东省中医院生物资源库的中医诊断为湿证的DKD患者的粪便标本和血清标本,应用16s RNA高通量测序和液相色谱-质谱法(LC-MS)检测DKD不同湿证亚型(湿热证、水湿证、湿浊证)患者之间的差异肠道菌群和血清代谢物,探索与湿证亚型相关的代谢通路,并将肠道微生物与代谢组学相结合,探讨肠道菌群和血清代谢物的关联性。结果 研究共纳入41例DKD患者的粪便和血清标本,其中湿热证21例,水湿证13例,湿浊证7例;肠道微生物结果显示:水湿证和湿浊证的差异肠道菌群有7种,湿浊证和湿热证有13种,水湿证和湿热证有4种。代谢组学结果提示:DKD湿浊证和湿热证的差异血清代谢物有8种,主要富集在苯丙氨酸代谢和泛醌和其他萜类醌生物合成通路(P<0.05);水湿证和湿热证有27种,主要富集在嘌呤代谢通路和缬氨酸、亮氨酸和异亮氨酸生物合成通路;水湿证和湿浊证有16种,主要富集在α-亚麻酸代谢通路(P<0.05)。肠道菌群与代谢组学关联分析显示:共有46种差异血清代谢物与差异肠道菌群相关,主要富集在苯丙氨酸代谢通路。结论 DKD中医湿证亚型(湿浊证、湿热证、水湿证)之间存在差异肠道菌群、血清代谢物,与差异肠道菌群关联后,这些差异血清代谢在苯丙氨酸代谢途径中富集。
英文摘要:
      Objective To investigate the distinct intestinal microbiota and potential biomarkers associated with diabetic kidney disease (DKD).Methods Stool specimens and serum specimens from patients with DKD with Chinese medicine(CM) diagnosis of dampness syndrome stored in the biorepository of Guangdong Provincial Hospital of Traditional Chinese Medicine from Jan 2017 to Dec 2019 were included,and 16s RNA high-throughput sequencing and liquid chromatography-mass spectrometry (LC-MS) were applied to detect the differential intestinal flora and serum metabolites among patients with different dampness syndrome subtypes of DKD (damp heat syndrome,water dampness syndrome,and dampness turbidity syndrome).The metabolic pathways associated with dampness subtypes and the association between intestinal flora and serum metabolites by combining intestinal microbiology and metabolomics were explored.Results A total of 41 patients with DKD were included in the study,including 21 with damp heat syndrome,13 with water dampness syndrome and 7 with dampness turbidity syndrome.The results of intestinal microorganism showed that there were 7 kinds of intestinal flora in the difference between water dampness syndrome and dampness turbidity syndrome.Similarly,there were 13 kinds of dampness turbidity syndrome and dampness heat syndrome,and 4 kinds of water dampness syndrome and dampness heat syndrome.The results of metabolomics showed that there were 8 kinds of metabolites in the blood of DKD with dampness turbidity syndrome and dampness heat syndrome,which were mainly concentrated in phenylalanine metabolism and ubiquinone and other terpenoid quinone biosynthesis pathway(P<0.05).There were 27 kinds of water dampness syndrome and damp heat syndrome,which were mainly concentrated in purine metabolism pathway and valine,leucine and isoleucine biosynthesis pathway.There were 16 kinds of water dampness syndrome and dampness turbidity syndrome,which were mainly concentrated in α- Linolenic acid metabolism pathway (P<0.05).The correlation analysis between intestinal flora and metabolomics showed that there were 46 kinds of differential blood metabolites in CM dampness syndrome of DKD,which were mainly concentrated in phenylalanine metabolic pathway.Conclusion There are differential intestinal flora,serum metabolites between the damp subtypes of DKD(dampness and turbidity,dampheat,and waterdampness),and upon association with differential intestinal flora,these differential serum metabolites are enriched in the phenylalanine metabolic pathway.
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