妊娠期糖尿病患者治疗前后肠道菌群的不同特征及其与血糖水平的关系

Q4 Medicine

中华围产医学杂志 Pub Date : 2020-02-16 DOI:10.3760/CMA.J.ISSN.1007-9408.2020.02.005

Yu Liu, Jing-mei Ma, S. Qin, B. Zhu, Fei Liu, Huixia Yang

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The V3-V4 region of the 16S rRNA gene was sequenced on the Illumina Hiseq 2500 platform, and the results were analyzed. QIIME software was used for bioinformatics analysis. Student's t-test, Mann-Whitney U test, and Chi-square test were used for statistical analysis. \n \n \nResults \n(1) Before treatment, the Alpha diversity of the GDM group was significantly reduced compared with that of the control group (Chao1 index: 443.9±72.9 vs 474.0±63.3, t=2.104, P<0.05; Shannon index: 5.6±0.5 vs 6.0±0.5, t=2.002, P<0.05), and a significant difference in Beta diversity was also observed between the two groups (R2=0.04, P<0.05). However, a significant difference was shown in neither Alpha nor Beta diversity between the two groups after the treatment. 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引用次数: 0

摘要

目的了解妊娠期糖尿病（GDM）患者治疗前后肠道微生物特征，以及肠道微生物群与75g口服葡萄糖耐量试验（OGTT）血糖水平的关系。方法2016年10月至2017年12月在北京大学第一医院进行前瞻性队列嵌套病例对照研究。涉及45例妊娠24-28周的GDM妊娠（GDM组）和45例年龄和孕前体重指数（BMI）匹配的健康孕妇（对照组）。在治疗前（24-28孕周）和治疗后（36-40孕周）采集所有参与者的粪便样本。在Illumina Hiseq 2500平台上对16S rRNA基因的V3-V4区域进行测序，并对结果进行分析。QIME软件用于生物信息学分析。采用Student t检验、Mann-Whitney U检验和卡方检验进行统计分析。结果（1）治疗前，GDM组的α多样性与对照组相比显著降低（Chao1指数：443.9±72.9 vs 474.0±63.3，t=2.104，P<0.05；Shannon指数：5.6±0.5 vs 6.0±0.5，t=2.002，P<0.05），β多样性在两组之间也有显著差异（R2=0.04，P<0.05），治疗后两组之间的Alpha和Beta多样性均未显示出显著差异。（2）治疗前，GDM组的Blautia和Faecalibacterium的相对丰度显著高于对照组[M（P25-P75）：0.016（0.009-0.022）vs 0.011（0.007-0.016），U=720.000；0.114（0.076-0.141）vs 0.091（0.061-0.126），U=752.000；均P<0.05]，但Akkermansia的相对丰度，Odoribacter和Butyricimonas显著降低[0001（0.000-0.002）vs 0.001（0.000-0.005），U=745.000；0.001（0.000=0.004）vs 0.004（0.001-0.006），U=766.500；0.001（0.001-0.003）vs 0.003（0.001-0.005）；U=710.000；均P<0.05。（3）OGTT的空腹血糖水平与阿克曼菌的相对丰度呈负相关，Odoribacter和Butyricimonas（r=-0.325、-0.273和-0.284；均P<0.05），以及1小时OGTT葡萄糖水平与Akkermansia和Butyrcimonas的相对丰度之间（r=-0.285和-0.265，均P<0.05）。2小时OGTT血糖水平与Faecalibacterium的相对丰度呈正相关（r=0.278，P<0.05），但与阿克曼菌的相对丰度呈负相关（r=-0.245，P<0.05）。OGTT时间-葡萄糖曲线下面积与阿克曼氏菌和丁酸杆菌的相对丰度呈正相关（r=-0.1321和-0.264，均P<0.05），其与OGTT血糖水平显著相关。GDM治疗后血糖升高可改善肠道微生物群紊乱。关键词：糖尿病，妊娠期；胃肠道微生物组；葡萄糖耐量试验；血糖

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Different characteristics of gut microbiota before and after management of women with gestational diabetes mellitus and the association with blood glucose level

Objective To investigate the gut microbial profiles of gestational mellitus diabetes (GDM) patients before and after treatment, and the relationship between gut microbiota and blood glucose level measured in 75 g oral glucose tolerance test (OGTT). Methods A prospective cohort-based nested case-control study was conducted in Peking University First Hospital from October 2016 to December 2017. Forty-five pregnancies at 24-28 gestational weeks with GDM (GDM group) and 45 healthy gravidas (control group) matched for age and pre-pregnancy body mass index (BMI) were involved. Stool samples of all participants were collected before (24-28 gestational weeks) and after (36-40 gestational weeks) treatment. The V3-V4 region of the 16S rRNA gene was sequenced on the Illumina Hiseq 2500 platform, and the results were analyzed. QIIME software was used for bioinformatics analysis. Student's t-test, Mann-Whitney U test, and Chi-square test were used for statistical analysis. Results (1) Before treatment, the Alpha diversity of the GDM group was significantly reduced compared with that of the control group (Chao1 index: 443.9±72.9 vs 474.0±63.3, t=2.104, P<0.05; Shannon index: 5.6±0.5 vs 6.0±0.5, t=2.002, P<0.05), and a significant difference in Beta diversity was also observed between the two groups (R2=0.04, P<0.05). However, a significant difference was shown in neither Alpha nor Beta diversity between the two groups after the treatment. (2) Before treatment, the relative abundances of Blautia and Faecalibacterium of the GDM group were significantly higher than those of the control group [M (P25-P75): 0.016 (0.009-0.022) vs 0.011 (0.007-0.016), U=782.000; 0.114 (0.076-0.141) vs 0.091 (0.061-0.126), U=752.000; both P<0.05], but the relative abundances of Akkermansia, Odoribacter and Butyricimonas were significantly lower [0.001 (0.000-0.002) vs 0.001 (0.000-0.005), U=745.000; 0.001 (0.000-0.004) vs 0.004 (0.001-0.006), U=766.500; 0.001 (0.000-0.003) vs 0.003 (0.001-0.005), U=710.000; all P<0.05]. (3) A negative relationship was found between the fasting glucose level of OGTT and the relative abundances of Akkermansia, Odoribacter and Butyricimonas (r=-0.325, -0.273 and -0.284; all P<0.05), and between the one-hour-OGTT glucose level and the relative abundances of Akkermansia and Butyricimonas (r=-0.285 and -0.265, both P<0.05). The two-hour-OGTT glucose level was positively related to the relative abundance of Faecalibacterium (r=0.278, P<0.05), but negatively related to the relative abundance of Akkermansia (r=-0.245, P<0.05). The area under the OGTT time-glucose curve was negatively related to the relative abundances of Akkermansia and Butyricimonas (r=-0.321 and -0.264, both P<0.05). Conclusions There are significant differences in gut microbial composition and structure between GDM and healthy pregnant women, which are significantly associated with OGTT blood glucose level. Euglycemia achieved after GDM management could improve gut microbiota disorder. Key words: Diabetes, gestational; Gastrointestinal microbiome; Glucose tolerance test; Blood glucose

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来源期刊

中华围产医学杂志 Medicine-Obstetrics and Gynecology

CiteScore

0.70

自引率

0.00%

发文量

4446

期刊介绍： Chinese Journal of Perinatal Medicine was founded in May 1998. It is one of the journals of the Chinese Medical Association, which is supervised by the China Association for Science and Technology, sponsored by the Chinese Medical Association, and hosted by Peking University First Hospital. Perinatal medicine is a new discipline jointly studied by obstetrics and neonatology. The purpose of this journal is to "prenatal and postnatal care, improve the quality of the newborn population, and ensure the safety and health of mothers and infants". It reflects the new theories, new technologies, and new progress in perinatal medicine in related disciplines such as basic, clinical and preventive medicine, genetics, and sociology. It aims to provide a window and platform for academic exchanges, information transmission, and understanding of the development trends of domestic and foreign perinatal medicine for the majority of perinatal medicine workers in my country.