Abstract

The human gut microbiome can modulate metabolic health and affect insulin resistance, and it may play an important role in the etiology of gestational diabetes mellitus (GDM). Here, we compared the gut microbial composition of 43 GDM patients and 81 healthy pregnant women via whole-metagenome shotgun sequencing of their fecal samples, collected at 21–29 weeks, to explore associations between GDM and the composition of microbial taxonomic units and functional genes. A metagenome-wide association study identified 154 837 genes, which clustered into 129 metagenome linkage groups (MLGs) for species description, with significant relative abundance differences between the 2 cohorts. Parabacteroides distasonis, Klebsiella variicola, etc., were enriched in GDM patients, whereas Methanobrevibacter smithii, Alistipes spp., Bifidobacterium spp., and Eubacterium spp. were enriched in controls. The ratios of the gross abundances of GDM-enriched MLGs to control-enriched MLGs were positively correlated with blood glucose levels. A random forest model shows that fecal MLGs have excellent discriminatory power to predict GDM status. Our study discovered novel relationships between the gut microbiome and GDM status and suggests that changes in microbial composition may potentially be used to identify individuals at risk for GDM.

Highlights

  • Human gut microbiome can modulate metabolic health and affect insulin resistance, and may play an important role in the etiology of gestational diabetes mellitus (GDM).Here, we compared the gut microbial composition of 43 GDM patients and 81 healthy pregnant women via whole-metagenome shotgun sequencing of their fecal samples collecting at 21-29 weeks, to explore associations between GDM and the composition of microbial taxonomic units and functional genes

  • Our study discovered novel relationships between gut microbiome and GDM status, and suggested that changes in microbial composition may potentially be used to identify individuals at risk for GDM

  • Metagenome-wide association study (MGWAS) identified 154,837 genes, which enabled to cluster into 129 metagenome linkage groups (MLGs) for species description, with significant abundance differences between two cohorts

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Summary

Methods

Study population and samplingAs part of the Born in Guangzhou Cohort Study (BIGCS), fecal samples were obtained from 124pregnant women during their second trimester in Guangzhou Women and Children’s MedicalCenter (GWCMC). As part of the Born in Guangzhou Cohort Study (BIGCS), fecal samples were obtained from 124. Pregnant women during their second trimester in Guangzhou Women and Children’s Medical. Pregnant women who had severe obstetric complications (GDM excluded) such as pregnancy-induced hypertension, preeclampsia, or eclampsia, were excluded. Study subjects had not received any antibiotic treatment within 1 month of sample collection and had not ingested yogurt within 2 weeks of sample collection. This study received approval from the Ethics Committee of GWCMC, and written informed consent was obtained from all participating pregnant women. Eligible participants underwent a standard 2h 75g oral glucose tolerance test (OGTT) between 21–29 weeks’ gestation by collection of 2ml blood samples fasting, 1h, and 2h after a 75g glucose load, using NaF/EDTA tubes. Plasma glucose was measured by a hexokinase method using Beckman Coulter

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