Distribution Characteristics Of Gut Microbiota In Pregnant Women With Gestational Diabetes Mellitus

Background:Gestational diabetes mellitus(GDM)is a common complication in the perinatal period.It is associated with many adverse outcomes such as premature delivery,fetal death,macrosomia,and maternal and infant type 2 diabetes.The incidence rate is gradually increasing.GDM is a metabolic disease.GDM patients show pathophysiological changes such as insufficient insulin secretion,decreased insulin sensitivity,and abnormal glucose metabolism.Advanced maternal age(AMA)is one of the high-risk factors of GDM.The incidence of metabolic diseases such as GDM in AMA significantly increased.Studies have found that changes in gut microbiota and its metabolites accompany or promote changes in human energy metabolism,and gut microbiota imbalance is closely related to metabolic diseases such as diabetes and dyslipidemia.The interaction between age and gut microbiota may be one of the factors influencing the occurrence and development of GDM.In this study,16S rRNA sequencing was used to further study the changes of gut microbiota in pregnant women with GDM,especially the gut microbiota characteristics in AMA with GDM.Methods:1.Changes of gut microbiota in pregnant women with GDMGather the patients who underwent prenatal examination and glucose tolerance screening in the outpatient department of obstetrics of Nanfang hospital from December 2017 to August 2018.The medical history,health measurement and blood test results were collected.Fecal specimens were collected according to the standard.Total DNA was extracted,followed by the performance of 16S rRNA V4 gene PCR amplification and Illumina sequencing.2.Gut microbiota characteristics in AMA with GDMThe GDM patients were divided in AMA group and NMA group according to maternal age.Bioinformatics analysis and statistical processing were used to study the characteristics of gut microbiota in different age groups.Results:1.Changes of gut microbiota in pregnant women with GDM1.1 47 cases in the GDM group and 85 cases in the non-GDM group were enrolled.There are no statistical differences of age,maternal parity,multiple birth,blood pressure,hemoglobin levels,thyroid dysfunction,Lipoprotein levels between the two groups.The average pre-pregnancy BMI in the diabetic group was higher than that in the non-diabetic group,P=0.022.The prevalence o’f overweight and obesity in the GDM group was higher,and the difference was statistically significant,P=0.004.There was no significant difference in perinatal BMI between the two groups,but the average weight gain during pregnancy was significantly higher in the GDM group than in the non-GDM group,P<0.001.1.2 Significant changes occurred in the gut microbiota of GDM group.There’s no significant difference in a diversity analysis between two groups.In the PCoA analysises showed that genus from two groups were able to cluster within group and be distinguished sig,nificantly between groups,P<0.05.At the phylum level,gut microbiota of GDM group have a lower proportion of Firmicutes and higher proportion of Bcateroidetes and Proteobacteria.LEFSe analysis shows Firmicutes-Clostridia-Clostridieales-Ruminococcaceae that were divided into Firmicutes are the characteristic strains in the non-GDM group.Proteobacteria,Enterobacteriaceae,Enterobacteriales,and Gammaproteobacter are characteristic strains in the GDM group.Firmicutes are negatively correlated with perinatal HbAlc,negatively correlated with perinatal fasting blood glucose,Ruminococcaceae is negatively correlated with perinatal fasting blood glucose,and Proteobacteria are positively correlated with perinatal fasting blood glucose.2.Gut microbiota characteristics in AMA with GDM2.1 Among GDM patients,23 were AMA and 24 were NMA.There were no statistically significant differences between the two groups in terms of parity,multiple birth,blood pressure,hemoglobin level,and blood lipids.There were no significant differences in body weight-related indicators such as pre-pregnancy BMI,prenatal BMI,and weight gain during pregnancy.2.2 Compared with NMA-GDM women,AMA-GDM showed significant decrease in a-related indicators such as Chao 1 index,PD index and observed OTUs(P<0.05).Unweighted PCoA analysis could be clustered within the group.Significant distinctions indicate a significant difference in beta diversity between the two groups(P<0.05),At the phylum level,AMA-GDM group have a lower proportion of Firmicutes,Bacteroidetes and proteobacteria but a higher proportion of Actionbacteria.The results of LEFSe suggest that the 8-Proteobacteria-Desulfovation family are the characteristic strains of the AMA-GDM group,and Synergistales and y-proteobacteria are characteristic strains of the NMA-GDM group.Desulfovibrio and Oscillospira are negatively correlated with perinatal HbAlc.ConclusionGDM group have a lower proportion of Firmicutes and higher proportion of Bacteroidetes and Proteobacteria.Characteristic strains in the GDM group cluster in Proteobacteria.The abundance of intestinal microbiota decreased in AMA-GDM group.AMA-GDM group have a lower proportion of Firmicutes,Bacteroidetes and proteobacteria but a higher proportion of Actionbacteria.Characteristic strains in the AMA-GDM group cluster in 8-Proteobacteria.Age plays a role in the occurrence and development of diseases by affecting the composition and metabolic patterns of intestinal microbiota.Analysis and understanding of gut microbiota characteristics in pregnant women can be used as a potential screening tool and therapeutic target.