Comparative Studies of the Gut Microbiota in the Offspring of Mothers With and Without Gestational Diabetes.

Background: Offspring of mothers with gestational diabetes mellitus (GDM) have increased risk of developing metabolic disorders as they grow up. Microbial colonization of the newborn gut and environmental exposures affecting the configuration of the gut microbiota during infancy have been linked to increased risk of developing disease during childhood and adulthood. In a convenience sample, we examined whether the intestinal tract of children born to mothers with GDM is differentially colonized in early life compared to offspring of mothers with normal gestational glucose regulation. Secondly, we examined whether any such difference persists during infancy, thus potentially conferring increased risk of developing metabolic disease later in life. Methods: Fecal samples were collected from children of mothers with (n = 43) and without GDM (n = 82) during the first week of life and again at an average age of 9 months. The gut microbiota was characterized by 16S rRNA gene amplicon sequencing (V1-V2). Differences in diversity and composition according to maternal GDM status were assessed, addressing potential confounding by mode of delivery, perinatal antibiotics treatment, feeding and infant sex. Results: Children of mothers with GDM were featured by a differential composition of the gut microbiota, both during the first week of life and at 9 months, at higher taxonomic and OTU levels. Sixteen and 15 OTUs were differentially abundant after correction for multiple testing during the first week of life and at 9 months, respectively. Two OTUs remained differentially abundant after adjustment for potential confounders both during the first week of life and at 9 months. Richness (OTU) was decreased in neonates born to mothers with GDM; however, at 9 months no difference in richness was observed. There was no difference in Shannon's diversity or Pielou's evenness at any timepoint. Longitudinally, we detected differential changes in the gut microbiota composition from birth to infancy according to GDM status. Conclusion: Differences in glycaemic regulation in late pregnancy is linked with relatively modest variation in the gut microbiota composition of the offspring during the first week of life and 9 months after birth.

Gestational diabetes and the human salivary microbiota: a longitudinal study during pregnancy and postpartum.

BACKGROUND: An aberrant composition of the salivary microbiota has been found in individuals with type 2 diabetes, and in pregnant women salivary microbiota composition has been associated with preeclampsia and pre-term birth. Pregnant women, who develop gestational diabetes (GDM), have a high risk of developing type 2 diabetes after pregnancy. In the present study we assessed whether GDM is linked to variation in the oral microbial community by examining the diversity and composition of the salivary microbiota. METHOD: In this observational study the salivary microbiota of pregnant women with GDM (n = 50) and normal glucose regulation (n = 160) in third trimester and 9 months postpartum was assessed by 16S rRNA gene amplicon sequencing of the V1-V3 region. GDM was diagnosed in accordance with the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria. Cross-sectional difference in alpha diversity was assessed using Student's t-test and longitudinal changes were assessed by mixed linear regression. Cross-sectional and longitudinal difference in beta diversity was assessed by permutational multivariate analyses of variance. Differentially abundant genera and OTUs were identified by negative binomial regression. RESULTS: In the third trimester, two species-level operational taxonomic units (OTUs), while eight OTUs postpartum were differentially abundant in women with GDM compared with normoglycaemic women. OTU richness, Shannon diversity and Pielou evenness decreased from late pregnancy to 9 months after delivery regardless of glycaemic status. CONCLUSION: GDM is associated with a minor aberration of the salivary microbiota during late pregnancy and postpartum. For unknown reasons richness of the salivary microbiota decreased from late pregnancy to postpartum, which might be explained by the physiological changes of the immune system during human pregnancy.

Gestational diabetes is associated with change in the gut microbiota composition in third trimester of pregnancy and postpartum.

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.

Ponderal index at birth associates with later risk of gestational diabetes mellitus.

PURPOSE: Low birth weight (BW) and low ponderal index (PI) are associated with increased risk of type 2 diabetes mellitus. This study has two purposes: first to investigate the influence of PI on the risk of gestational diabetes mellitus (GDM); second, to study the association between glucose metabolism and BW in women with previous GDM. METHODS: GDM cohort: 185 women with GDM in 1978-1996, attending a follow-up study in 2000-2002. Control cohort: 1137 women from a population-based diabetes screening study (Inter99) in a neighbouring county in 1999-2001. BW and birth length were collected from the original midwifery records. BW and PI were stratified into tertiles for analysis. RESULTS: PI in the lower tertiles was associated with an increased risk of GDM [odds ratio 1.59 (95% confidence interval 1.07-2.36, p = 0.021)]. Among women with previous GDM, the area under the curve (AUC) for plasma levels of glucose and insulin during an OGTT was highest for the lower tertiles of BW (for AUCglucose p = 0.048, for AUCinsulin p = 0.047 adjusted for age and BMI). CONCLUSIONS: Lower PI is associated with increased risk of GDM. In women with previous GDM, lower BW is associated with a more severe impairment of glucose metabolism one to two decades after the pregnancy complicated by GDM.

A Time Interval of More Than 18 Months Between a Pregnancy and a Roux-en-Y Gastric Bypass Increases the Risk of Iron Deficiency and Anaemia in Pregnancy.

OBJECTIVE: The aim of the study is to explore the impact of time between Roux-en-Y gastric bypass (RYGB) and pregnancy on obstetrical outcome and nutritional derangements. METHODS: In a retrospective cross-sectional study of pregnant women admitted for antenatal care at two tertiary hospitals, we examined 153 women with RYGB and a singleton pregnancy of at least 24 weeks. The women were stratified according to a pregnancy <18 months (40 women) or ≥18 months (113 women) after RYGB. Main outcome measures were nutritional parameters and glycated haemoglobin 1Ac (HbA1c) in second and third trimester of pregnancy, gestational hypertension, length of pregnancy, mode of delivery and foetal birth weight. RESULTS: The two groups were comparable regarding age, parity and prepregnancy body mass index. The frequency of iron deficiency anaemia (ferritin <12 µg/L and haemoglobin <6.5 mmol/L/10.5 g/dL) was significantly higher in the late group, 29 vs. 8 % in the early group, p = 0.010. No differences were found for vitamin B12, vitamin D and zinc. Median HbA1c was significantly higher in the late group than in the early group (33 vs. 31 mmol/mol, p = 0.027). There were no significant differences in the risk of adverse pregnancy outcome or birth weight between the two groups. CONCLUSION: A long surgery-to-pregnancy time interval after a RYGB increases the risk of iron deficiency anaemia but not of other nutritional deficits. Time interval does not seem to have an adverse effect on the obstetrical outcome, including intrauterine growth restriction. Specific attention is needed on iron deficit with increasing surgery-to-pregnancy time interval.