Changes in the gut microbiota composition during pregnancy in patients with gestational diabetes mellitus (GDM)

Ilario Ferrocino,Fabio Broglio,Filomena Leone,Rosalba Rosato,Maurizio Cassader,Simona Bo,Adriana Zarovska,Roberto Gambino,Valentina Ponzo,Clara Monzeglio,Angelo Romano,Ilaria Goitre,Giorgio Grassi,Luca Cocolin

doi:10.1038/s41598-018-30735-9

Abstract

Gestational diabetes mellitus (GDM), a common pregnancy complication, is associated with an increased risk of maternal/perinatal outcomes. We performed a prospective observational explorative study in 41 GDM patients to evaluate their microbiota changes during pregnancy and the associations between the gut microbiota and variations in nutrient intakes, anthropometric and laboratory variables. GDM patients routinely received nutritional recommendations according to guidelines. The fecal microbiota (by 16S amplicon-based sequencing), was assessed at enrolment (24–28 weeks) and at 38 weeks of gestational age. At the study end, the microbiota α-diversity significantly increased (P < 0.001), with increase of Firmicutes and reduction of Bacteroidetes and Actinobacteria. Patients who were adherent to the dietary recommendations showed a better metabolic and inflammatory pattern at the study-end and a significant decrease in Bacteroides. In multiple regression models, Faecalibacterium was significantly associated with fasting glucose; Collinsella (directly) and Blautia (inversely) with insulin, and with Homeostasis-Model Assessment Insulin-Resistance, while Sutterella with C-reactive protein levels. Consistent with this latter association, the predicted metagenomes showed a correlation between those taxa and inferred KEGG genes associated with lipopolysaccharide biosynthesis. A higher bacterial richness and strong correlations between pro-inflammatory taxa and metabolic/inflammatory variables were detected in GDM patients across pregnancy. Collectively these findings suggest that the development of strategies to modulate the gut microbiota might be a potentially useful tool to impact on maternal metabolic health.

Highlights

Gestational diabetes mellitus (GDM), a common pregnancy complication, is associated with an increased risk of maternal/perinatal outcomes
Dysbiosis among GDM patients was reported to be associated with a few genus belonging to Firmicutes, Bacteroides and Actinobacteria phyla of the gut microbiota and the observed main differences in comparison to healthy women are relative to the gene contents of the gut microbes[13]
Our results showed a shift in the microbiota composition from the second to the third trimester of pregnancy, with higher α-diversity, Firmicutes increment, and Bacteroidetes and Actinobacteria reduction

Summary

Introduction

Gestational diabetes mellitus (GDM), a common pregnancy complication, is associated with an increased risk of maternal/perinatal outcomes. During the course of normal pregnancy, gut microbiota has been reported to remain relatively stable[11] or to change dramatically, with an increase in Proteobacteria and Actinobacteria, a decline in butyrate-producing bacteria, a reduction in bacterial richness and within-subject (α) diversity, and higher between-subject (β) diversity at the end of pregnancy[3]. These modifications were supposed to favor the metabolic changes which support the healthy fetal growth, such as reduced insulin sensitivity and increased nutrient absorption[3,7]. The aims of our study were evaluating: i) whether the within-patient gut microbiota composition varied from the second to the third trimester of pregnancy; ii) whether patients with greater adherence to dietary recommendations presented a different microbial pattern than the less adherent ones; iii) whether changes in microbiota composition were associated with variations in nutrient intakes, anthropometric and laboratory variables; iv) whether specific microbiota oligotypes were implicates in these associations

Objectives

Methods

Results

Conclusion