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Gestational Diabetes Is Uniquely Associated With Altered Early Seeding of the Infant Gut Microbiota.

ABSTRACT: Gestational diabetes mellitus (GDM) is a worldwide public health problem affecting up to 27% of pregnancies with high predictive values for childhood obesity and inflammatory diseases. Compromised seeding of the infant gut microbiota is a risk factor for immunologic and metabolic diseases in the offspring; however, how GDM along with maternal obesity interact to alter colonization remains unknown. We hypothesized that GDM individually and in combination with maternal overweight/obesity would alter gut microbial composition, diversity, and short-chain fatty acid (SCFA) levels in neonates. We investigated 46 full-term neonates born to normal-weight or overweight/obese mothers with and without GDM, accounting for confounders including cesarean delivery, lack of breastfeeding, and exposure to antibiotics. Gut microbiota in 2-week-old neonates born to mothers with GDM exhibited differences in abundance of 26 microbial taxa; 14 of which showed persistent differential abundance after adjusting for pre-pregnancy BMI. Key pioneering gut taxa, including potentially important taxa for establishing neonatal immunity, were reduced. Lactobacillus, Flavonifractor, Erysipelotrichaceae, and unspecified families in Gammaproteobacteria were significantly reduced in neonates from mothers with GDM. GDM was associated with an increase in microbes involved in suppressing early immune cell function (Phascolarctobacterium). No differences in infant stool SCFA levels by maternal phenotype were noted; however, significant correlations were found between microbial abundances and SCFA levels in neonates. Our results suggest that GDM alone and together with maternal overweight/obesity uniquely influences seeding of specific infant microbiota in patterns that set the stage for future risk of inflammatory and metabolic disease.

SUBMITTER: Soderborg TK

PROVIDER: S-EPMC7729132 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Gestational Diabetes Is Uniquely Associated With Altered Early Seeding of the Infant Gut Microbiota.

Soderborg Taylor K TK Carpenter Charles M CM Janssen Rachel C RC Weir Tiffany L TL Robertson Charles E CE Ir Diana D Young Bridget E BE Krebs Nancy F NF Hernandez Teri L TL Barbour Linda A LA Frank Daniel N DN Kroehl Miranda M Friedman Jacob E JE

Frontiers in endocrinology 20201127

Gestational diabetes mellitus (GDM) is a worldwide public health problem affecting up to 27% of pregnancies with high predictive values for childhood obesity and inflammatory diseases. Compromised seeding of the infant gut microbiota is a risk factor for immunologic and metabolic diseases in the offspring; however, how GDM along with maternal obesity interact to alter colonization remains unknown. We hypothesized that GDM individually and in combination with maternal overweight/obesity would alt ...[more]

PMID: 33329403

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Project description:Gestational diabetes mellitus (GDM) is a unique form of glucose intolerance, in that it is transient and solely occurs in pregnancy. Pregnancies with GDM are at high risk of developing preeclampsia (PE), a leading cause of fetal and maternal morbidity or mortality. Since PE is associated with excessive activation of circulatory neutrophils and occurrence of neutrophil extracellular traps (NETs) in affected placentae, we examined these features in cases with GDM, as this could be a feature linking the two conditions. Our data indicate that neutrophil activity is indeed altered in GDM, exhibiting pronounced activation and spontaneous generation of NETs by isolated neutrophils in in vitro culture. In this manner, GDM may similarly affect neutrophil behavior and NET formation as witnessed in other forms of diabetes, with the addition of the physiological changes mediated by pregnancy. Since circulatory TNF-α levels are elevated in cases with GDM, a feature also observed in this study, we examined whether this pro-inflammatory cytokine contributed to neutrophil activation. By using infliximab, a clinically utilized TNF-α antagonist, we observed that the pro-NETotic effect of GDM sera was significantly reduced. We also detected pronounced neutrophil infiltrates in placentae from GDM cases. The occurrence of NETs in these tissues is suggested by the extracellular co-localization of citrullinated histones and myeloperoxidase. In addition, elevated neutrophil elastase (NE) mRNA and active enzymatic protein were also detected in such placentae. This latter finding could be important in the context of previous studies in cancer or diabetes model systems, which indicated that NE liberated from infiltrating neutrophils enters surrounding cells, altering cell signaling by the degradation of IRS1. These findings could potentiate the underlying inflammatory response process in GDM and possibly open an avenue for the therapeutic interventions in gestational hyperglycemia.

Project description:Gestational diabetes mellitus (GDM), a high-risk pregnancy complication of great effect on the perinatal health of women and newborns, may cause changes of gut microbiota in mothers and further affect gut microbiota in newborns. This study aimed to investigate the potential effect of mother GDM on newborns' gut microbiota. Meconium DNA was extracted from a total of 34 full-term and C-sectioned newborns, in which 20 newborns had mothers diagnosed with GDM, while 14 had unaffected mothers. Sequencing and bioinformatics analysis of 16S rRNA indicated that the gut microbiota of GDM newborns showed differences compared to control newborns. The taxonomy analyses suggested that the overall bacterial content significantly differed by maternal diabetes status, with the microbiome of the GDM group showing lower alpha-diversity than that of control group. The phyla of Proteobacteria and Actinobacteria in GDM newborns increased, while that of Bacteroidetes significantly reduced (P<0.05). Moreover, several unique gut microbiota in phylum of Proteobacteria, Firmicutes, Actinobacteria, Bacteroidetes, Chloroflexi, Acidobacteria, and Planctomycetes found in control newborns were absent in GDM ones. At genus level, the relative abundance of Prevotella and Lactobacillus significantly decreased (P<0.05) in GDM newborns. Correlation analysis indicated that maternal fasting glucose levels were positively correlated with the relative abundance of phylum Actinobacteria and genus Acinetobacter, while negatively correlated with that of phylum Bacteroidetes and genus Prevotella. However, bacteria in GDM grade A2 (GDM_A2) newborns did not show any statistical variation compared to those from control newborns, which might be attributed to the additional intervention by insulin. The results of this study have important implications for understanding the potential effects of GDM on the gut microbiota of newborns and thus possibly their metabolism at later stages in their lives.

Project description:Women with gestational diabetes mellitus (GDM) have different gut microbiota in late pregnancy compared to women without GDM. It remains unclear whether alterations of gut microbiota can be identified prior to the diagnosis of GDM. This study characterized dynamic changes of gut microbiota from the first trimester (T1) to the second trimester (T2) and evaluated their relationship with later development of GDM. Compared with the control group (n?=?103), the GDM group (n?=?31) exhibited distinct dynamics of gut microbiota, evidenced by taxonomic, functional, and structural shifts from T1 to T2. Linear discriminant analysis (LDA) revealed that there were 10 taxa in T1 and 7 in T2 that differed in relative abundance between the GDM and control groups, including a consistent decrease in the levels of Coprococcus and Streptococcus in the GDM group. While the normoglycemic women exhibited substantial variations of gut microbiota from T1 to T2, their GDM-developing counterparts exhibited clearly reduced inter-time point shifts, as corroborated by the results of Wilcoxon signed-rank test and balance tree analysis. Moreover, cooccurrence network analysis revealed that the interbacterial interactions in the GDM group were minimal compared with those in the control group. In conclusion, lower numbers of dynamic changes in gut microbiota in the first half of pregnancy are associated with the development of GDM.IMPORTANCE GDM is one of the most common metabolic disorders during pregnancy and is associated with adverse short-term and long-term maternal and fetal outcomes. The aim of this study was to examine the connection between dynamic variations in gut microbiota and development of GDM. Whereas shifts in gut microbiota composition and function have been previously reported to be associated with GDM, very little is known regarding the early microbial changes that occur before the diagnosis of GDM. This study demonstrated that the dynamics in gut microbiota during the first half of pregnancy differed significantly between GDM and normoglycemic women. Our findings suggested that gut microbiota may potentially serve as an early biomarker for GDM.

Dataset Information

Gestational Diabetes Is Uniquely Associated With Altered Early Seeding of the Infant Gut Microbiota.

Publications

Gestational Diabetes Is Uniquely Associated With Altered Early Seeding of the Infant Gut Microbiota.

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