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Gut Microbiome and Serum Metabolic Alterations in Recurrent Gestational Diabetes Mellitus

ABSTRACT:

Gestational diabetes mellitus (GDM) is a common complication of pregnancy, particularly affecting multiparous women with a history of GDM, who face a recurrence risk approaching 50%. This study investigates the association between gut microbiota modifications and metabolic profiles from early to mid-pregnancy and the recurrence of GDM in a cohort of 70 multiparous women with prior GDM. Conducted as a prospective cohort study at Beijing Obstetrics and Gynecology Hospital from July 2018 to December 2020, participants underwent assessments including oral glucose tolerance tests (OGTT) and collection of fecal and serum samples. Microbial DNA was extracted, with the V3-V4 region of the 16S rRNA gene sequenced, while serum metabolites were analyzed through non-targeted metabolomics using mass spectrometry. Results indicated significant alterations in gut microbiota composition, with specific genera associated with increased GDM risk. Notably, the study identified distinct metabolic patterns, revealing downregulation of several key metabolites in recurrent GDM cases compared to controls. Pathway enrichment analysis highlighted dysregulation in metabolic functions pertinent to serotonergic synapses, arachidonic acid metabolism, unsaturated fatty acid biosynthesis, and caffeine metabolism. Overall, this research underscores the critical role of gut microbiota and metabolic changes in understanding GDM recurrence, providing insights that may inform targeted preventive strategies.

INSTRUMENT(S): Liquid Chromatography MS - positive, Liquid Chromatography MS - negative - hilic

PROVIDER: MTBLS12326 | MetaboLights | 2025-07-21

REPOSITORIES: MetaboLights

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			Action	DRS
	HFX8_1807137_CN_QC1.mzML	Mzml
	HFX8_1807137_CN_QC10.mzML	Mzml
	HFX8_1807137_CN_QC11.mzML	Mzml
	HFX8_1807137_CN_QC12.mzML	Mzml
	HFX8_1807137_CN_QC13.mzML	Mzml

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Project description:Background - Prepregnancy overweight and obesity promote deleterious health impacts on both mothers during pregnancy and the offspring. Significant changes in the maternal peripheral blood mononuclear cells (PBMCs) gene expression due to obesity are well-known. However, during pregnancy the impact of overweight on immune cell gene expression and its association with maternal and infant outcomes is not well explored. Methods – Blood samples were collected from healthy normal weight (NW, BMI 18.5-24.9) or overweight (OW, BMI 25-29.9) 2nd parity pregnant women at 12, 24 and 36 weeks of pregnancy. PBMCs were isolated from the blood and subjected to mRNA sequencing. Maternal and infant microbiota were analyzed by 16S rRNA gene sequencing. Integrative multi-omics data analysis was performed to evaluate the association of gene expression with maternal diet, gut microbiota, milk composition, and infant gut microbiota. Results - Gene expression analysis revealed that 453 genes were differentially expressed in the OW women compared to NW women at 12 weeks of pregnancy, out of which 354 were upregulated and 99 were downregulated. Several up-regulated genes in the OW group were enriched in inflammatory, chemokine-mediated signaling and regulation of interleukin-8 production-related pathways. At 36 weeks of pregnancy healthy eating index score was positively associated with several genes that include, DTD1, ELOC, GALNT8, ITGA6-AS1, KRT17P2, NPW, POT1-AS1 and RPL26. In addition, at 36 weeks of pregnancy, genes involved in adipocyte functions, such as NG2 and SMTNL1, were negatively correlated to human milk 2’FL and total fucosylated oligosaccharides content collected at 1 month postnatally. Furthermore, infant Akkermansia was positively associated with maternal PBMC anti-inflammatory genes that include CPS1 and RAB7B, at 12 and 36 weeks of pregnancy. Conclusions – These findings suggest that prepregnancy overweight impacts the immune cell gene expression profile, particularly at 12 weeks of pregnancy. Further, deciphering the complex association of PBMC’s gene expression levels with maternal gut microbiome and milk composition and infant gut microbiome may aid in developing strategies to mitigate obesity-mediated effects.

Project description:Objectives: Arterial hypertension (AH) influences salivary gland physiology and oral health, being associated with a higher incidence of periodontal disease in pregnant women. Evidence points to a bidirectional relationship between the oral microbiota and blood pressure regulation. Therefore, this study aimed to characterize the oral health of pregnant women and AH-associated changes in the salivary proteome and microbiome during pregnancy and postpartum. Design: Ten healthy women and ten women with AH were enrolled. Saliva was collected during pregnancy and six months postpartum. The salivary proteome was characterized by shotgun label-free mass spectrometry analysis. Specific proteins were validated through parallel reaction monitoring (PRM). The oral microbiota was characterized via 16S rRNA gene amplicon sequencing (V4 region). The periodontal health and the caries history was assessed during pregnancy. Results: Pregnant women with AH had lower junction plakoglobin (JUP)- and desmoplakin (DSP)-specific peptide levels than healthy women, confirmed by the PRM approach. The levels of these proteins correlated negatively with periodontal health indexes, which were higher in pregnant women with AH. In AH, nitrate-reducing microorganisms had lower abundance, correlating positively with JUP and DSP-specific peptides. Conclusions: The salivary proteome and microbiota are shaped by AH during and after pregnancy. Further research is required to understand the underlying mechanisms impairing oral health in AH. Data acquisition has been supported by EPIC-XS, project number 393, funded by the Horizon 2020 program of the European Union and the National Institute for Neurological Research (Programme EXCELES, ID Project No. LX22NPO5107) and the MEYS/EU project OP JAK-MULTIOMICS_CZ - Multi-omics platform for the search for biological correlates of diseases and the development of new diagnostic, preventive and therapeutic procedures (CZ.02.01.01/00/23_020/0008540).

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Gut Microbiome and Serum Metabolic Alterations in Recurrent Gestational Diabetes Mellitus

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