Difference in Gut Microbiota between the First and the Second Trimester of Pregnancy and the Association of Gut Microbiota with Gestational Diabetes Mellitus: A Prospective Cohort Study

  Objective  To characterize the characteristics of gut microbiota and its function in the first (T1) to second trimester(T2) of pregnancy and to evaluate its association with gestational mellitus diabetes (GDM).

  Methods  A prospective cohort study was conducted in Peking Union Medical College Hospital from May to December 2017. The pregnancies were divided into GDM group and non-GDM group (control group) according to the Results of 75 g oral glucose tolerance test at 24 to 48 weeks of gestation. Stool samples of all participants were collected in the first and the second trimester. The V4 region of the 16S rRNA gene was sequenced and analyzed. Multivariate Logistic regression analysis was used to investigate the relationship between Alpha diversity, relative abundance of intestinal flora and GDM.

  Results  A total of 145 pregnancies, of whom 34 diagnosed with GDM (GDM group) and 111 healthy (control group) were analyzed. The Alpha diversity of the GDM group (Shannon index and Simpson index) was significantly lower than that of the control group (P < 0.05). LEfSe analysis revealed that the relative abundance of several genera was different between the 2 groups in T1 or T2. Multivariate Logistic analysis showed that Shannon index ≤6.51 (OR=3.15, 95% CI: 1.32-7.52), Simpson index ≤0.96 (OR=2.54, 95% CI: 1.09-5.89), the lower relative abundance of Alloprevotella(OR=2.65, 95% CI: 1.09-6.44) and Lachnospira(OR=3.17, 95% CI: 1.33-7.55) in the first trimester were risk factors for GDM. The pathways of LPS biosynthesis, energy metabolism, glucose metabolism and amino acid metabolism of gut microbiome revealed through the Tax4Fun analysis were significantly enriched in the GDM group in T2.

  Conclusions  Compared with healthy controls, the functional characteristics of intestinal microflora in GDM patients during the second trimester were significantly enriched in functional pathways related to LPS synthesis, energy metabolism, glucose metabolism and amino acid metabolism. The decreases of the diversity as well as the relative abundance of some genus in the early pregnancy are the risk factors for GDM.