Novo Nordisk Foundation Center for Basic Metabolic Research, Section for Metabolic Genetics, Faculty of Health and Medical Science, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen N, Denmark.
Department of Clinical Epidemiology, Bispebjerg and Frederiksberg Hospital, Hovedvejen 5, Nordre Fasanvej 57, 2000, Frederiksberg, Copenhagen, Denmark.
Microbiome. 2018 May 15;6(1):89. doi: 10.1186/s40168-018-0472-x.
Imbalances of gut microbiota composition are linked to a range of metabolic perturbations. In the present study, we examined the gut microbiota of women with gestational diabetes mellitus (GDM) and normoglycaemic pregnant women in late pregnancy and about 8 months postpartum.
Gut microbiota profiles of women with GDM (n = 50) and healthy (n = 157) pregnant women in the third trimester and 8 months postpartum were assessed by 16S rRNA gene amplicon sequencing of the V1-V2 region. Insulin and glucose homeostasis were evaluated by a 75 g 2-h oral glucose tolerance test during and after pregnancy.
Gut microbiota of women with GDM was aberrant at multiple levels, including phylum and genus levels, compared with normoglycaemic pregnant women. Actinobacteria at phylum level and Collinsella, Rothia and Desulfovibrio at genus level had a higher abundance in the GDM cohort. Difference in abundance of 17 species-level operational taxonomic units (OTUs) during pregnancy was associated with GDM. After adjustment for pre-pregnancy body mass index (BMI), 5 of the 17 OTUs showed differential abundance in the GDM cohort compared with the normoglycaemic pregnant women with enrichment of species annotated to Faecalibacterium and Anaerotruncus and depletion of species annotated to Clostridium (sensu stricto) and to Veillonella. OTUs assigned to Akkermansia were associated with lower insulin sensitivity while Christensenella OTUs were associated with higher fasting plasma glucose concentration. OTU richness and Shannon index decreased from late pregnancy to postpartum regardless of metabolic status. About 8 months after delivery, the microbiota of women with previous GDM was still characterised by an aberrant composition. Thirteen OTUs were differentially abundant in women with previous GDM compared with women with previous normoglycaemic pregnancy.
GDM diagnosed in the third trimester of pregnancy is associated with a disrupted gut microbiota composition compared with normoglycaemic pregnant women, and 8 months after pregnancy, differences in the gut microbiota signatures are still detectable. The gut microbiota composition of women with GDM, both during and after pregnancy, resembles the aberrant microbiota composition reported in non-pregnant individuals with type 2 diabetes and associated intermediary metabolic traits.
肠道微生物群落组成的失衡与一系列代谢紊乱有关。本研究旨在探讨妊娠期糖尿病(GDM)和血糖正常孕妇在妊娠晚期和产后 8 个月的肠道微生物群。
采用 16S rRNA 基因 V1-V2 区扩增子测序分析 GDM 组(n=50)和健康对照组(n=157)孕妇在妊娠晚期和产后 8 个月的肠道微生物群。通过妊娠期间和之后的 75g 2 小时口服葡萄糖耐量试验评估胰岛素和葡萄糖稳态。
与血糖正常孕妇相比,GDM 孕妇的肠道微生物群在多个水平上存在异常,包括门和属水平。厚壁菌门在门水平和柯林斯氏菌属、罗氏菌属和脱硫弧菌属在属水平的丰度较高。妊娠期间 17 个种水平操作分类单元(OTUs)的丰度差异与 GDM 相关。调整孕前体重指数(BMI)后,与血糖正常孕妇相比,GDM 组有 5 个 OTUs 的丰度存在差异,其中丰度较高的OTUs 注释为粪杆菌属和厌氧真杆菌属,丰度较低的 OTUs 注释为梭菌(严格意义上)和韦荣球菌属。阿克曼氏菌属的 OTUs 与较低的胰岛素敏感性相关,而克里斯滕森氏菌属的 OTUs 与空腹血糖浓度升高相关。无论代谢状态如何,从妊娠晚期到产后,OTU 丰富度和香农指数都有所下降。产后约 8 个月,既往 GDM 妇女的肠道微生物群仍表现为异常组成。与既往血糖正常妊娠的妇女相比,既往 GDM 妇女有 13 个 OTUs 存在差异。
妊娠晚期诊断的 GDM 与血糖正常孕妇相比,肠道微生物群组成发生紊乱,产后 8 个月仍可检测到肠道微生物群特征的差异。GDM 孕妇在妊娠期间和之后的肠道微生物群组成与非妊娠 2 型糖尿病患者和相关中间代谢特征的异常微生物群组成相似。