Alterations of gut microbiota in gestational diabetes patients during the second trimester of pregnancy in the Shanghai Han population.
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ABSTRACT: Background
The causes of gestational diabetes mellitus (GDM) are still unclear. Recent studies have found that the imbalance of the gut microbiome could lead to disorders of human metabolism and immune system, resulting in GDM. This study aims to reveal the different gut compositions between GDM and normoglycemic pregnant women and find the relationship between gut microbiota and GDM.Methods
Fecal microbiota profiles from women with GDM (n = 21) and normoglycemic women (n = 32) were assessed by 16S rRNA gene sequencing. Fasting metabolic hormone concentrations were measured using multiplex ELISA.Results
Metabolic hormone levels, microbiome profiles, and inferred functional characteristics differed between women with GDM and healthy women. Additionally, four phyla and seven genera levels have different correlations with plasma glucose and insulin levels. Corynebacteriales (order), Nocardiaceae (family), Desulfovibrionaceae (family), Rhodococcus (genus), and Bacteroidetes (phylum) may be the taxonomic biomarkers of GDM. Microbial gene functions related to amino sugar and nucleotide sugar metabolism were found to be enriched in patients with GDM.Conclusion
Our study indicated that dysbiosis of the gut microbiome exists in patients with GDM in the second trimester of pregnancy, and gut microbiota might be a potential diagnostic biomarker for the diagnosis, prevention, and treatment of GDM.
SUBMITTER: Su Y
PROVIDER: S-EPMC8394568 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background: Dysbiosis of human gut microbiota is associated with a wide range of metabolic disorders, including gestational diabetes mellitus (GDM). Yet whether gut microbiota dysbiosis participates in the etiology of GDM remains largely unknown. Objectives: Our study was initiated to determine whether the alternations in gut microbial composition during early pregnancy linked to the later development of GDM, and explore the feasibility of microbial biomarkers for the early prediction of GDM. Study design: This nested case-control study was based upon an early pregnancy follow-up cohort (ChiCTR1900020652). Gut microbiota profiles of 98 subjects with GDM and 98 matched healthy controls during the early pregnancy (10-15 weeks) were assessed via 16S rRNA gene amplicon sequencing of V4 region. The data set was randomly split into a discovery set and a validation set, the former was used to analyze the differences between GDM cases and controls in gut microbial composition and functional annotation, and to establish an early identification model of GDM, then the performance of the model was verified by the external validation set. Results: Bioinformatic analyses revealed changes to gut microbial composition with significant differences in relative abundance between the groups. Specifically, Eisenbergiella, Tyzzerella 4, and Lachnospiraceae NK4A136 were enriched in the GDM group, whereas Parabacteroides, Megasphaera, Eubacterium eligens group, etc. remained dominant in the controls. Correlation analysis revealed that GDM-enriched genera Eisenbergiella and Tyzzerella 4 were positively correlated with fasting blood glucose levels, while three control-enriched genera (Parabacteroides, Parasutterella, and Ruminococcaceae UCG 002) were the opposite. Further, GDM functional annotation modules revealed enrichment of modules for sphingolipid metabolism, starch and sucrose metabolism, etc., while lysine biosynthesis and nitrogen metabolism were reduced. Finally, five genera and two clinical indices were included in the linear discriminant analysis model for the prediction of GDM; the areas under receiver operating characteristic curves of the training and validation sets were 0.736 (95% confidence interval: 0.663-0.808) and 0.696 (0.575-0.818), respectively. Conclusions: Gut bacterial dysbiosis in early pregnancy was found to be associated with the later development of GDM, and gut microbiota-targeted biomarkers might be utilized as potential predictors of GDM.
| S-EPMC7056672 | biostudies-literature
Project description:BACKGROUND:Imbalances of gut microbiota composition are linked to a range of metabolic perturbations. In the present study, we examined the gut microbiota of women with gestational diabetes mellitus (GDM) and normoglycaemic pregnant women in late pregnancy and about 8 months postpartum. METHODS:Gut microbiota profiles of women with GDM (n?=?50) and healthy (n?=?157) pregnant women in the third trimester and 8 months postpartum were assessed by 16S rRNA gene amplicon sequencing of the V1-V2 region. Insulin and glucose homeostasis were evaluated by a 75 g 2-h oral glucose tolerance test during and after pregnancy. RESULTS:Gut microbiota of women with GDM was aberrant at multiple levels, including phylum and genus levels, compared with normoglycaemic pregnant women. Actinobacteria at phylum level and Collinsella, Rothia and Desulfovibrio at genus level had a higher abundance in the GDM cohort. Difference in abundance of 17 species-level operational taxonomic units (OTUs) during pregnancy was associated with GDM. After adjustment for pre-pregnancy body mass index (BMI), 5 of the 17 OTUs showed differential abundance in the GDM cohort compared with the normoglycaemic pregnant women with enrichment of species annotated to Faecalibacterium and Anaerotruncus and depletion of species annotated to Clostridium (sensu stricto) and to Veillonella. OTUs assigned to Akkermansia were associated with lower insulin sensitivity while Christensenella OTUs were associated with higher fasting plasma glucose concentration. OTU richness and Shannon index decreased from late pregnancy to postpartum regardless of metabolic status. About 8 months after delivery, the microbiota of women with previous GDM was still characterised by an aberrant composition. Thirteen OTUs were differentially abundant in women with previous GDM compared with women with previous normoglycaemic pregnancy. CONCLUSION:GDM diagnosed in the third trimester of pregnancy is associated with a disrupted gut microbiota composition compared with normoglycaemic pregnant women, and 8 months after pregnancy, differences in the gut microbiota signatures are still detectable. The gut microbiota composition of women with GDM, both during and after pregnancy, resembles the aberrant microbiota composition reported in non-pregnant individuals with type 2 diabetes and associated intermediary metabolic traits.
| S-EPMC5952429 | biostudies-literature
Project description:BACKGROUND: Gestational diabetes mellitus (GDM) is one type of diabetes that presents during pregnancy and significantly increases the risk of a number of adverse consequences for the fetus and mother. The microRNAs (miRNA) have recently been demonstrated to abundantly and stably exist in serum and to be potentially disease-specific. However, no reported study investigates the associations between serum miRNA and GDM. METHODOLOGY/PRINCIPAL FINDINGS: We systematically used the TaqMan Low Density Array followed by individual quantitative reverse transcription polymerase chain reaction assays to screen miRNAs in serum collected at 16-19 gestational weeks. The expression levels of three miRNAs (miR-132, miR-29a and miR-222) were significantly decreased in GDM women with respect to the controls in similar gestational weeks in our discovery evaluation and internal validation, and two miRNAs (miR-29a and miR-222) were also consistently validated in two-centric external validation sample sets. In addition, the knockdown of miR-29a could increase Insulin-induced gene 1 (Insig1) expression level and subsequently the level of Phosphoenolpyruvate Carboxy Kinase2 (PCK2) in HepG2 cell lines. CONCLUSIONS/SIGNIFICANCE: Serum miRNAs are differentially expressed between GDM women and controls and could be candidate biomarkers for predicting GDM. The utility of miR-29a, miR-222 and miR-132 as serum-based non-invasive biomarkers warrants further evaluation and optimization.
| S-EPMC3161072 | biostudies-literature
Project description:Clinical gestational diabetes mellitus (GDM) is frequently associated with hyperlipidemia comorbidity. Altered human gut microbiome has been linked to GDM and hyperlipidemia, respectively but not the comorbid condition. We hypothesize that the occurrence of hyperlipidemia with GDM may be characterized by distinguishable gut microbiome and blood metabolomic patterns. We presented comprehensive microbiomic coupled with lipidomics analyses to characterize gut microbiota and lipometabolism of plasma samples in women with GDM only, hyperlipidemia only and those with diabetes plus hyperlipidemia, and to explore association of the gut microbiota composition with blood lipid profiles and clinical parameters of gestational diabetes with or without commodity. We found that the relative abundance of bacterial taxa Streptococcus, Faecalibacterium, Veillonella, Prevotella, Haemophilus and Actinomyces was significantly higher in diabetes plus hyperlipidemia cohorts. Moreover, several bacteria were correlated with fasting plasma glucose and blood lipid levels of the participants with GDM and hyperlipidemia. The altered plasma lipidome in subjects with diabetes plus hyperlipidemia suggested that characteristic blood lipid profiles were associated with the pathogenesis of gestational diabetes plus hyperlipidemia. Collectively, this study provides insights on changes in fecal microbiota and plasma lipidome to predict and characterize the development of gestational diabetes with lipid metabolic abnormality.
| S-EPMC6691352 | biostudies-literature
Project description:Interest in the high folate status of pregnant women has increased due to its role in the prevention of neural tube defects (NTDs). The effect of increased red blood cell (RBC) folate status during the second trimester of pregnancy on gestational diabetes mellitus (GDM) remains unclear. We measured RBC folate concentrations by competitive protein-binding assay and obtained clinical information from electronic medical records. Logistic regression analysis was used to explore the associations of RBC folate concentrations with risks of gestational diabetes mellitus (GDM). We further assessed the potential nonlinear relations between continuous log-transformed RBC folate concentrations and GDM risk by using the restricted cubic splines. We observed high RBC folate concentrations in GDM patients compared to control group [median (interquartile range, IQR), GDM vs. controls: 1,554.03 (1,240.54-1,949.99) vs. 1,478.83 (1,124.60-1,865.71) nmol/L, p = .001]. Notably, high folate concentrations were significantly associated with an increased risk of GDM [RR per 1-SD increase: 1.16 (1.03, 1.30), p = .012] after adjustment for maternal age, parity, and body mass index (BMI) at enrollment. In the restricted cubic spline model, a test of the null hypothesis of the linear relationship was rejected (p = .001). Our study firstly showed that maternal RBC folate concentrations during the second trimester of pregnancy increase the risk of GDM in a Chinese population. Further randomized clinical trials (RCTs) are warranted to confirm the adverse effect.
| S-EPMC6848811 | biostudies-literature
Project description:AimTo investigate the differences in gut microbiota composition among nonpregnant women of reproductive age, healthy pregnant women, and gestational diabetes (GD) patients.MethodsA total of 45 outpatients were enrolled and divided into three groups: nonpregnant women of reproductive age (control group, n = 23), healthy pregnant women (normal group, n = 10), and GD patients (GD group, n = 12). Faecal samples were collected and sequenced using 16S rRNA gene sequencing to analyse the microbial composition.Results(1) Pregnant patients exhibited an increase in the abundance of Streptococcus (Pnormal = 0.01286, PGD = 0.002965) and Blautia (Pnormal = 0.0003924, PGD = 0.000246) but a decrease in the abundance of Roseburia (Pnormal = 0.0361, PGD = 0.007075), Phascolarctobacterium (Pnormal = 0.0003906, PGD = 0.02499) and Lachnoclostridium (Pnormal = 0.0003906, PGD = 0.03866). (2) Compared with healthy pregnant women, GD patients had an excessive increase in Streptococcus abundance and decrease in Roseburia abundance. The increase in Blautia abundance and the decrease in Phascolarctobacterium and Lachnoclostridium abundance in GD patients were less than those in healthy pregnant women. (3) The abundance of Faecalibacterium prausnitzii decreased significantly in GD patients (PGD = 0.02985) but not in healthy pregnant patients (Pnormal = 0.1643).ConclusionsAbnormal increases and decreases in the abundances of gut microbiota components, especially Faecalibacterium prausnitzii, were observed in GD patients.Trial registrationThe cross-sectional research was conducted in accordance with the Declaration of Helsinki, and approved by Sir Run Run Shaw Hospital Clinical Trials and Biomedical Ethics Committee. The study has been registered in the Chinese Clinical Trial Registry (ChiCTR1900026164, 24/09/2019, http://www.chictr.org.cn/showproj.aspx?proj=43,455 ).
| S-EPMC10983739 | biostudies-literature
Project description:Gestational diabetes mellitus (GDM), a common pregnancy complication, is associated with an increased risk of maternal/perinatal outcomes. We performed a prospective observational explorative study in 41 GDM patients to evaluate their microbiota changes during pregnancy and the associations between the gut microbiota and variations in nutrient intakes, anthropometric and laboratory variables. GDM patients routinely received nutritional recommendations according to guidelines. The fecal microbiota (by 16S amplicon-based sequencing), was assessed at enrolment (24-28 weeks) and at 38 weeks of gestational age. At the study end, the microbiota α-diversity significantly increased (P < 0.001), with increase of Firmicutes and reduction of Bacteroidetes and Actinobacteria. Patients who were adherent to the dietary recommendations showed a better metabolic and inflammatory pattern at the study-end and a significant decrease in Bacteroides. In multiple regression models, Faecalibacterium was significantly associated with fasting glucose; Collinsella (directly) and Blautia (inversely) with insulin, and with Homeostasis-Model Assessment Insulin-Resistance, while Sutterella with C-reactive protein levels. Consistent with this latter association, the predicted metagenomes showed a correlation between those taxa and inferred KEGG genes associated with lipopolysaccharide biosynthesis. A higher bacterial richness and strong correlations between pro-inflammatory taxa and metabolic/inflammatory variables were detected in GDM patients across pregnancy. Collectively these findings suggest that the development of strategies to modulate the gut microbiota might be a potentially useful tool to impact on maternal metabolic health.
| S-EPMC6093919 | biostudies-literature
Project description:ObjectiveWe aimed to systematically review available literature linking adipokines to gestational diabetes mellitus (GDM) for a comprehensive understanding of the roles of adipokines in the development of GDM.MethodsWe searched PubMed/MEDLINE and EMBASE databases for published studies on adipokines and GDM through October 21, 2014. We included articles if they had a prospective study design (i.e., blood samples for adipokines measurement were collected before GDM diagnosis). Random-effects models were used to pool the weighted mean differences comparing levels of adipokines between GDM cases and non-GDM controls.ResultsOf 1523 potentially relevant articles, we included 25 prospective studies relating adipokines to incident GDM. Our meta-analysis of nine prospective studies on adiponectin and eight prospective studies on leptin indicated that adiponectin levels in the first or early second trimester of pregnancy were 2.25 μg/ml lower (95% CI: 1.75-2.75), whereas leptin levels were 7.25 ng/ml higher (95% CI 3.27-11.22), among women who later developed GDM than women who did not. Prospective data were sparse and findings were inconsistent for visfatin, retinol binding protein (RBP-4), resistin, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and vaspin. We did not identify prospective studies for several novel adipokines, including chemerin, apelin, omentin, or adipocyte fatty acid-binding protein. Moreover, no published prospective studies with longitudinal assessment of adipokines and incident GDM were identified.ConclusionAdiponectin levels in the first or second trimester of pregnancy are lower among pregnant women who later develop GDM than non-GDM women, whereas leptin levels are higher. Well-designed prospective studies with longitudinal assessment of adipokines during pregnancy are needed to understand the trajectories and dynamic associations of adipokines with GDM risk.
| S-EPMC4625979 | biostudies-literature
Project description:IntroductionGestational Diabetes Mellitus (GDM) development is related to underlying metabolic syndrome that is associated with elevated complement C3 and C4. Elevated C3 levels have been associated with preeclampsia and the development of macrosomia.MethodsThis case-control study included 34 pregnant women with GDM and 16 non-diabetic (ND) women in their second trimester. Complement-related proteins were measured and correlated with demographic, biochemical, and pregnancy outcome data.ResultsGDM women were older with a higher BMI (p<0.001); complement C3, C4 and Factor-H were significantly elevated (p=0.001, p=0.05, p=0.01, respectively). When adjusted for age and BMI, Complement C3 (p=0.04) and Factor-H (p=0.04) remained significant. Partial correlation showed significant correlation between C4 with serum alanine aminotransferase (ALT) (p<0.05) and 2nd term diastolic blood pressure (p<0.05); Factor-H and C-reactive protein (CRP; p<0.05). Pearson bivariate analysis revealed significant correlations between C3, C4, and Factor-H and CRP; p<0.05; C3 and gestational age at delivery (GA; p<0.05); C4 and ALT and second-trimester systolic blood pressure (STBP) (p=0.008 and p<0.05, respectively); Factor-H and glycated hemoglobin (HbA1c) (p<0.05). Regression analysis showed that the elevation of C3 could be accounted for by age, BMI, GA and CRP, with CRP being the most important predictor (p=0.02). C4 elevation could be accounted for by ALT, CRP and STBP. CRP predicted Factor-H elevation.ConclusionThe increased C3, C4 and Factor-H during the second trimester of pregnancy in GDM are not independently associated with GDM; inflammation and high BMI may be responsible for their elevation. The elevation of second trimester C3 in GDM is associated with earlier delivery and further work is needed to determine if this is predictive.
| S-EPMC8043150 | biostudies-literature
Project description:We aimed to examine the prospective association between first trimester HbA1c and gestational diabetes (GDM) and explore the utility of HbA1c for prediction of GDM. We used data from a case-control study within the prospective NICHD Fetal Growth Studies-Singleton Cohort (2009-2013), which enrolled 2,802 women at 12 U.S. clinical centers. HbA1c was measured in GDM cases (n?=?107) and matched controls (n?=?214) targeted at 8-13, 16-22, 24-29, and 34-37 gestational weeks. We excluded women with HbA1c???6.5% (48?mmol/mol) at enrollment (n?=?3) or who had a hemoglobin variant (n?=?6). At 8-13 gestational weeks, women who later developed GDM had significantly higher HbA1c (5.3[standard deviation 0.3]%; 34[4]mmol/mol) than women without GDM (5.1[0.3]%; 32[3] mmol/mol) (P???0.001); this difference remained significant throughout pregnancy. Each 0.1% (1?mmol/mol) HbA1c increase at 8-13 weeks was associated with an adjusted 22% increased GDM risk (95% confidence interval 1.09-1.36). First trimester HbA1c significantly improved GDM prediction over conventional risk factors (AUC 0.59 vs 0.65; P?=?0.04). In conclusion, women who develop GDM may have impaired glucose homeostasis early in or prior to pregnancy, as indicated by their elevated first trimester HbA1c. First trimester HbA1c may aid in early identification of at risk women.
| S-EPMC6095876 | biostudies-other