The Association Between Gestational Diabetes Mellitus And Human Gut Microbiota

Objective:Gestational Diabetes Mellitus?GDM?is defined as impaired glucose tolerance with onset or first recognition during pregnancy.The incidence of GDM is increasing year by year across the world.The consequence of GDM is severe to both the mothers and their offspring.The human gut is home to a large number of microorganisms that have been found to be associated with numerous diseases,including GDM.However,studies on GDM and gut microbiota are still at the beginning stage,and most of the related results come from cross-sectional study design.To date,there is no published data based on prospective birth cohort to study the association between GDM and human gut microbiota.On the other hand,numerous researches on the association between type 2 diabetes mellitus?T2DM?and gut microbiome suggested that GDM could also significantly associated with gut microorganisms,since the two diseases shared a lot of similarities in both genetic and environmental risk factors.It is very likely that at as early as the 1^sttrimester of gestation before GDM diagnosis,the gut microbiome of GDM patients already possess certain characteristics that associated with GDM incidence and disease development.Such features in gut microbial community structure could be one of the cause to GDM,and could be used as biomarkers for disease prevention,early diagnosis,and treatments.This study was conducted based on prospective birth cohort,aiming to 1)investigate the association between gut microbiome and GDM at 1^stand2ⁿdd trimester,and 2)reveal the varied dynamics of gut microbiota in GDM and healthy women from early to middle stage of pregnancy.Methods:Based on the Chengdu Shuangliu cohort,the target population was enrolled in the early pregnancy?<18 weeks?,and the 75 g oral glucose tolerance test was performed in the mid-pregnancy?24-28 weeks?,26 GDM patients were screened out.At the same time,the fecal samples and clinical basic data were collected during the early pregnancy and the mid-pregnancy.According to case-control study,26healthy controls were matched with the age of pregnant women?±3 years?,baseline gestational age?±4 weeks?and sampling time?±4 weeks of gestation?.The DNA was extracted from the stool samples,and the V3-V4 region of the bacterial 16S rRNA gene was amplified by a two-step PCR and subsequently sequenced on an Illumina Miseq?PE300?platform.Results:There was no significant difference in?diversity between GDM group and the healthy control in the early pregnancy and the mid-pregnancy.The?diversity and the community structure of the GDM group and the healthy control did not change from the early pregnancy to the mid-pregnancy,but different Operational Taxonomic Units?OTUs?were found.When discussing the interaction between GDM status and pregnancy on gut microbiota,GDM status had an effect on community structure?P=0.026?,but the effect of pregnancy?P=0.74?and the interaction of GDM status and pregnancy?P=0.165?on community structure were not found.There was also no significant difference in community structure between the GDM group and the healthy controls at the early pregnancy?P=0.17?,but the difference in community structure between the two groups was statistically significant at the mid-pregnancy?P=0.028?.Simultaneously,we initially identified significantly different OTUs between GDM and controls for the early pregnancy as Gammaproteobacteria,Enterobacteriales,Enterobacteriaceae,Prevotella,Klebsiella and the mid-pregnancy as Enterobacteriaceae,Ruminococcaceae,Dorea.The microbiota composition of the study population could be divided into three enterotypes.When ignoring pairing,the GDM status of the people with enterotype 2?P=0.020?or with enterotype 3?P=0.035?in the mid-pregnancy would affect the community structure.Under the principle of the enterotype and matching,the pregnancy,GDM status and the interaction between the two would not affect the community structure of the people with enterotype 2.There was no correlation between other influencing factors,including pre-pregnancy BMI,weight gain,and the identified OTUs during pregnancy.Conclusions:The?diversity and community structure of gut microbiota did not change dynamically from the early pregnancy to the mid-pregnancy,but the different OTUs were found.Although there was no difference in community structure between GDM and the healthy control at the early pregnancy,the community structure had changed at the mid-pregnancy.The OTUs identified at the early pregnancy between cases and controls may indicate that some shifts had occurred in early pregnancy in GDM patients.