Abstract
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.
Highlights
Events occurring in early life, even prenatally, are known to affect the risk of developing childhood and adult disease (Catalano and deMouzon, 2015; Wallace et al, 2016)
Normal glucose regulation or gestational diabetes mellitus (GDM) was determined from of an 75 g 2 h (2-h) oral glucose tolerant test (OGTT) performed in pregnant women of third trimester according to the International Association of the Diabetes and Pregnancy Study Group criteria for GDM diagnosis (International Association of Diabetes Pregnancy Study Groups, 2010), resulting in 43 offspring born to mothers with GDM and 82 offspring born to mothers with normal gestational plasma glucose regulation, forward referred to as “mothers without GDM”
Two children born to mothers with GDM and three children born to mothers without GDM were born preterm
Summary
Events occurring in early life, even prenatally, are known to affect the risk of developing childhood and adult disease (Catalano and deMouzon, 2015; Wallace et al, 2016). Recent studies have shown that human meconium contains bacterial DNA and specific bacteria fed to pregnant mice are detectable in the meconium of the offspring, suggesting that colonization of the fetal gastrointestinal tract may occur intrauterine and is directly influenced by maternal environmental exposures (Jiménez et al, 2008; Hu et al, 2013). 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. We examined whether any such difference persists during infancy, potentially conferring increased risk of developing metabolic disease later in life
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