妊娠期糖尿病与妊娠晚期和产后肠道微生物群组成的变化有关
Crusell et al. Microbiome (2018)
DOI 10.1186/s40168-018-0472-x
妊娠期糖尿病与妊娠晚期和产后肠道微生物群组成的变化有关
Gestational diabetes is associated withchange in the gut microbiota composition in third trimester of pregnancy andpostpartum
Abstract
Background: Imbalances of gut microbiota composition are linked to a range ofmetabolic perturbations. In the present study, we examined the gut microbiotaof women with gestational diabetes mellitus (GDM) and normoglycaemic pregnantwomen in late pregnancy and about 8 months postpartum.
Methods: Gut microbiota profiles of women with GDM (n = 50) and healthy (n= 157) pregnant women in the third trimester and 8 months postpartum wereassessed by 16S rRNA gene amplicon sequencing of the V1-V2 region. Insulin andglucose homeostasis were evaluated by a 75 g 2-h oral glucose tolerance testduring and after pregnancy.
Results: 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 Desulfovibrioat genus level had a higher abundance in the GDM cohort. Difference inabundance of 17 species- level operational taxonomic units (OTUs) duringpregnancy was associated with GDM. After adjustment for pre-pregnancy body massindex (BMI), 5 of the 17 OTUs showed differential abundance in the GDM cohortcompared with the normoglycaemic pregnant women with enrichment of speciesannotated to Faecalibacterium and Anaerotruncus and depletion of speciesannotated to Clostridium (sensustricto) and to Veillonella. OTUsassigned to Akkermansia wereassociated with lower insulin sensitivity while Christensenella OTUs were associated with higher fasting plasmaglucose concentration. OTU richness and Shannon index decreased from latepregnancy to postpartum regardless of metabolic status. About 8 months afterdelivery, the microbiota of women with previous GDM was still characterised byan aberrant composition. Thirteen OTUs were differentially abundant in womenwith previous GDM compared with women with previous normoglycaemic pregnancy.
Conclusion: GDM diagnosed in the third trimester of pregnancy is associatedwith a disrupted gut microbiota composition compared with normoglycaemicpregnant women, and 8 months after pregnancy, differences in the gut microbiotasignatures are still detectable. The gut microbiota composition of women withGDM, both during and after pregnancy, resembles the aberrant microbiotacomposition reported in non-pregnant individuals with type 2 diabetes andassociated intermediary metabolic traits.
妊娠会引起代谢和免疫改变，其特征是胰岛素抵抗性增强和对对胎儿和胎盘的免疫耐受性增强。在易感女性中，这些生理变化可能导致妊娠期糖尿病(GDM)的发生。即使血糖调节在分娩后不久就恢复正常，但患有GDM的妇女在10 - 15年期间患2型糖尿病的风险会增加40%。有研究显示肠道微生物可能参与糖尿病的发病过程。本研究通过16s rRNA基因检测，对比GDM孕妇和健康孕妇的肠道微生物组成结构，发现两组存在显著差异，并且这个差异会持续到产后。
研究对象：丹麦50例妊娠期糖尿病孕妇（GDM）和157例健康孕妇。
入组条件：孕27-33周；单胎；丹麦白种人；有正常血糖妊娠史的多胞胎孕妇；入组时无子痫前期诊断；排除2个月内服用抗生素的孕妇。
研究方法：受试者在入组时（孕27-33孕周）和产后8个月进行问卷调查、空腹血检、标准2h口服葡萄糖耐量检测（OGTT）等生化检测，并且在OGTT48小时内采集粪便样本。
检测方法：16S rRNA基因V1-V2区测序等
研究结果：
与正常孕妇相比，GDM孕妇肠道菌群在门属等多个水平上均存在异常。门水平的放线菌和属水平的柯林斯菌属（Collinsella）、罗氏菌属（Rothia）和脱磷孤菌属（Desulfovibrio）在GDM组中丰度较高。
妊娠期17个种水平OTUs丰度存在差异，这与GDM有关。对妊娠前BMI进行调整后，与健康孕妇（粪便杆菌和厌氧菌丰富，梭菌和韦氏杆菌贫乏）相比，GDM队列中17个OTUs中有5个在GDM队列中显示出不同的丰度，。
Akkermansia的OTUs与较低的胰岛素敏感性有关，而Christensenella的OTUs与较高的空腹血糖浓度有关。无论代谢状态如何，从妊娠晚期到产后，OTU丰富度和Shannon指数均呈下降趋势。
与健康孕妇相比，妊娠晚期确诊的GDM肠道菌群组成紊乱，妊娠8个月后，肠道菌群特征的差异仍可检测到。
Fig. 2 Taxonomicbiomarkers of gestational diabetes during pregnancy and postpartum. Cladogram (a, c) and scores(b, d) of taxonomic biomarkers down to genus level identified by lineardiscriminant analysis (LDA) using LEfSe during pregnancy (a, b) and postpartum(c, d). Colour indicates the group in which a differentially abundant taxon isenriched (red: GDM and previous GDM; blue: normoglycaemic and previousnormoglycaemic pregnancy)
图2. 妊娠期及产后糖尿病分类标志物。利用lefse在妊娠期（a，b）和产后（c，d）进行线性判别分析（lda），确定分类生物标记的分类图（a，c）和得分（b，d），直至属水平。颜色表示一个分类群丰富的差异（红色：GDM和产前GDM；蓝色：正常血糖和产前正常血糖妊娠）
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