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首页|妊娠期糖尿病患者肠道菌群特征与妊娠期高血压疾病的关联研究

妊娠期糖尿病患者肠道菌群特征与妊娠期高血压疾病的关联研究

ssociation of Gut Microbiota with Hypertensive Disorders in Patients with Gestational Diabetes Mellitus

中文摘要英文摘要

背景 ?患有妊娠期糖尿病(GDM)的孕妇常合并妊娠期高血压疾病(HDP),进而严重影响妊娠期健康及分娩结局。肠道菌群与妊娠健康关系受到越来越多的关注,但其与GDM合并HDP的关联还有待研究。目的 ?探究GDM患者肠道菌群特征与并发 HDP 的关联。方法 ?以2019年8月至2020年1月在杭州市妇产科医院行产前检查的204例GDM患者为研究对象。仅确诊GDM的孕妇作为 GDM 组(n=181),同时确诊GDM和HDP的孕妇作为GDM合并 HDP 组(n=23)。收集入组孕妇的临床资料与炎症检测指标,并留取同期粪便样本进行肠道菌群16s rDNA扩增子测序分析;采用LEfSe分析,在门、科和属水平分别对两组孕妇肠道菌群的组成结构进行比较,识别各组明显富集的菌群;通过 Logistic 回归分析探索 GDM 合并 HDP 相关的肠道菌群特征;采用Spearman秩相关分析探究肠道菌群与炎症指标的关联。结果 ?两组肠道菌群组成及主要门水平上的菌群相对丰度比较,差异无统计学意义(P>0.05)。LEfSe分析结果:科水平分析显示,与GDM组相比,韦荣氏菌科(Veillonellaceae)在GDM合并HDP组明显富集(P<0.05),而柔膜菌纲RF39未分类菌科(Mollicutes RF39 unclassified family)和毛螺菌科(Lachnospiraceae)的相对丰度降低(P<0.05);属水平分析显示,GDM 组与 GDM 合并 HDP 组比较,小杆菌属(Dialister)、肠杆菌属(Intestinibacter)、真杆菌属(Eubacterium)和副萨特氏菌属(Parasutterella)在GDM合并HDP组明显富集(P<0.05),嗜木聚糖真杆菌属([Eubacterium] xylanophilum group)、Ruminiclostridium 6、柔膜菌纲 RF39 未分类菌属(Mollicutes RF39 unclassified genus)和毛螺菌科未分类菌属(Lachnospiraceae unclassified genus)在GDM组明显富集(P<0.05)。Logistic回归分析结果显示,Veillonellaceae(OR=1.06,95%CI=1.01~1.11)、Dialister(OR=1.26,95%CI=1.10~1.45)、Intestinibacter(OR=2.07,95%CI=1.12~3.84) 丰度上升是GDM孕 妇 合 并HDP的 独 立 危 险 因 素(P<0.05);Lachnospiraceae unclassified genus(OR=0.24,95%CI=0.08~0.75)丰度上升是GDM孕妇合并HDP的保护因素(P<0.05)。Spearman 秩相关分析结果显示,Veillonellaceae 与单核细胞比例呈正相关(rs=0.149,P<0.05);Dialister 与白细胞计数、嗜酸粒细胞比例、嗜酸粒细胞计数呈正相关(rs=0.151、0.163、0.171,P<0.05)。结论 ?Veillonellaceae、Dialister、Intestinibacter 丰度上升是GDM孕妇合并HDP的独立危险因素,Lachnospiraceae unclassified genus 丰度上升是GDM孕妇合并HDP的保护因素,其中Veillonellaceae、Dialister与多项炎症指标正相关,肠道菌群可能是GDM合并HDP的重要风险因子。

Background??Pregnant women with gestational diabetes mellitusGDMare often comorbid with hypertensive disorders of pregnancyHDPwhich can severely impact pregnancy health and delivery outcomes. The relationship between gut microbiota and pregnancy health has received increasing attentionbut its association with concurrent HDP in GDM remains to be investigated. Objective ?To explore the association between gut microbiota characteristics and concurrent HDP in GDM patients. Methods ?The 204 patients with GDM who underwent prenatal examination at the Obstetrics and Gynecology Hospital of Hangzhou from August 2019 to January 2020 were selected as the study subjects. Pregnant women diagnosed with GDM only were categorized as the GDM groupn=181while those concurrently diagnosed with GDM and HDP were categorized as the GDM with concurrent HDP groupn=23. Clinical data and inflammation detection markers of the enrolled pregnant women were collectedand fecal samples of the same period were retained for gut microbiota 16s rDNA amplicon sequencing analysis. LEfSe analysis was used to compare microbiota composition between the two groups at the phylumfamily and genus levelsand to identify distinct bacterial enrichments. Logistic regression analysis was performed to identify gut microbiota characteristics associated with concurrent HDP in GDM. Spearman's rank correlation analysis was performed to explore the association between gut microbiota and inflammatory markers. Results ?No significant differences were found in overall gut microbiota composition and relative abundances of major phyla between the two groupsP>0.05. LEfSe analysis on family level showed that the Veillonellaceae?family was enriched in the GDM with concurrent HDP groupP<0.05while Mollicutes RF39 unclassified family?and Lachnospiraceae?were depletedP<0.05. At the genus levelDialisterIntestinibacterEubacterium and Parasutterella?were enriched in the GDM with concurrent HDP groupP<0.05whereas Eubacterium xylanophilum groupRuminiclostridium 6Mollicutes RF39 unclassified genus?and Lachnospiraceae unclassified genus?were enriched in the GDM groupP<0.05. Logistic regression analysis results showed increased abundances of VeillonellaceaeOR=1.0695%CI=1.01~1.11DialisterOR=1.2695%CI=1.10~1.45and IntestinibacterOR=2.0795%CI=1.12~3.84were independent risk factors for concurrent HDP in GDMP<0.05while increased Lachnospiraceae was a protective factorP<0.05. Spearman's rank correlation analysis results showed Veillonellaceae?was positively correlated with the proportion of monocytesrs=0.149P<0.05Dialister?was positively correlated with leukocyte counteosinophil leukocyteand eosinophil countrs=0.1510.1630.171P<0.05. Conclusion ?Increased abundances of VeillonellaceaeDialister?and Intestinibacter?are independent risk factors for concurrent HDP in GDM pregnant womenwhile increased abundance of Lachnospiraceae unclassified genus?is a protective factor. Veillonellaceae?and Dialister?are positively correlated with multiple inflammatory markers. Gut microbiota may be an important risk factor for concurrent HDP in GDM.

高畅、梁新袖、卢莎、华雯、代愉恒、胡文胜、郑钜圣

10.12114/j.issn.1007-9572.2023.0321

妇产科学基础医学微生物学

糖尿病,妊娠高血压,妊娠性肠道菌群LEfSe 分析炎症影响因素分析

iabetes,gestationalHypertension,pregnancy-inducedIntestinal floraLEfSe analysisInflammationRoot cause analysis

高畅,梁新袖,卢莎,华雯,代愉恒,胡文胜,郑钜圣.妊娠期糖尿病患者肠道菌群特征与妊娠期高血压疾病的关联研究[EB/OL].(2023-08-16)[2025-07-16].https://chinaxiv.org/abs/202308.00199.点此复制

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