中国全科医学 ›› 2024, Vol. 27 ›› Issue (02): 156-162.DOI: 10.12114/j.issn.1007-9572.2023.0321

所属专题: 内分泌代谢性疾病最新文章合集 高血压最新文章合集

• 论著 • 上一篇    下一篇

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

代愉恒1, 高畅2, 梁新袖2, 卢莎1,3, 华雯4, 郑钜圣2,*(), 胡文胜1,3,*()   

  1. 1310008 浙江省杭州市妇产科医院
    2310024 浙江省杭州市,西湖大学生命科学学院
    3310008 浙江省杭州市,杭州师范大学附属妇产科医院
    4310053 浙江省杭州市,浙江中医药大学第四临床医学院
  • 收稿日期:2023-06-20 修回日期:2023-08-01 出版日期:2024-01-15 发布日期:2023-10-23
  • 通讯作者: 郑钜圣, 胡文胜

  • 作者贡献:郑钜圣进行文章的构思与研究的设计;高畅、梁新袖、卢莎、华雯进行数据收集及整理;梁新袖进行统计学处理;代愉恒、高畅负责撰写论文,进行结果的分析与解释;胡文胜进行论文的修订,负责文章的质量控制及审校。
  • 基金资助:
    国家自然科学基金面上项目(82173530); 浙江省科学技术厅"尖兵""领雁"研发攻关计划项目(2022C03102); 浙江省自然科学基金(LQ21H040001)

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

DAI Yuheng1, GAO Chang2, LIANG Xinxiu2, LU Sha1,3, HUA Wen4, ZHENG Jusheng2,*(), HU Wensheng1,3,*()   

  1. 1Hangzhou Women's Hospital, Hangzhou 310008, China
    2School of Life Sciences, Westlake University, Hangzhou 310024, China
    3The Affiliated Hangzhou Women's Hospital of Hangzhou Normal University, Hangzhou 310008, China
    4The Fourth Clinical School of Zhejiang Chinese Medicine University, Hangzhou 310053, China
  • Received:2023-06-20 Revised:2023-08-01 Published:2024-01-15 Online:2023-10-23
  • Contact: ZHENG Jusheng, HU Wensheng

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—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,与GDM组相比,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);与GDM合并HDP组相比,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与多项炎症指标呈正相关,肠道菌群可能是GDM合并HDP的重要风险因子。

关键词: 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

Abstract:

Background

Pregnant women with gestational diabetes mellitus (GDM) are often comorbid with hypertensive disorders of pregnancy (HDP), which can severely impact pregnancy health and delivery outcomes. The relationship between gut microbiota and pregnancy health has received increasing attention, but 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 Hangzhou Women's Hospital from August 2019 to January 2020 were selected as the study subjects. Pregnant women diagnosed with GDM only were categorized as the GDM group (n=181), while those concurrently diagnosed with GDM and HDP were categorized as the GDM with concurrent HDP group (n=23). Clinical data and inflammation detection markers of the enrolled pregnant women were collected, and 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 phylum, family and genus levels, and 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 groups (P>0.05). LEfSe analysis on family level showed that the Veillonellaceae family was enriched in the GDM with concurrent HDP group (P<0.05), while Mollicutes RF39 unclassified family and Lachnospiraceae were depleted (P<0.05). At the genus level, Dialister, Intestinibacter, Eubacterium and Parasutterella were enriched in the GDM with concurrent HDP group (P<0.05), whereas [Eubacterium] xylanophilum group, Ruminiclostridium 6, Mollicutes RF39 unclassified genus and Lachnospiraceae unclassified genus were enriched in the GDM group (P<0.05). Logistic regression analysis results showed increased abundances of Veillonellaceae (OR=1.06, 95%CI=1.01-1.11), Dialister (OR=1.26, 95%CI=1.10-1.45) and Intestinibacter (OR=2.07, 95%CI=1.12-3.84) were independent risk factors for concurrent HDP in GDM (P<0.05), while increased Lachnospiraceae was a protective factor (P<0.05). Spearman's rank correlation analysis results showed Veillonellaceae was positively correlated with the proportion of monocytes (rs=0.149, P<0.05) ; Dialister was positively correlated with leukocyte count, eosinophil leukocyte, and eosinophil count (rs=0.151, 0.163, 0.171, P<0.05) .

Conclusion

Increased abundances of Veillonellaceae, Dialister and Intestinibacter are independent risk factors for concurrent HDP in GDM pregnant women, while 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.

Key words: Diabetes, gestational, Hypertension, pregnancy-induced, Intestinal flora, LEfSe analysis, Inflammation, Root cause analysis