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

Abstract

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