Interaction and Metabolic Pathways: Elucidating the Role of Gut Microbiota in Gestational Diabetes Mellitus Pathogenesis

Abstract

Gestational diabetes mellitus (GDM) is a complex metabolic condition during pregnancy with an intricate link to gut microbiota alterations. Throughout gestation, notable shifts in the gut microbial component occur. GDM is marked by significant dysbiosis, with a decline in beneficial taxa like Bifidobacterium and Lactobacillus and a surge in opportunistic taxa such as Enterococcus. These changes, detectable in the first trimester, hint as the potential early markers for GDM risk. Alongside these taxa shifts, microbial metabolic outputs, especially short-chain fatty acids and bile acids, are perturbed in GDM. These metabolites play pivotal roles in host glucose regulation, insulin responsiveness, and inflammation modulation, which are the key pathways disrupted in GDM. Moreover, maternal GDM status influences neonatal gut microbiota, indicating potential intergenerational health implications. With the advance of multi-omics approaches, a deeper understanding of the nuanced microbiota-host interactions via metabolites in GDM is emerging. The reviewed knowledge offers avenues for targeted microbiota-based interventions, holding promise for innovative strategies in GDM diagnosis, management, and prevention.

Keywords: gestational diabetes mellitus; intestinal microbiota; metabolic disorders; metabolomics.

Figure 1

Impacts of gut microbiota and metabolic changes on gestational diabetes mellitus and long-term health outcomes.

Figure 2

Changes in GDM and healthy pregnancy gut microbes (genera) [32,33,34,35,36,37,39,40,46,49,50,54].

Figure 3

Gut microbes and their metabolites: possible mechanisms of GDM. TMAO Production: Gut microbiota significantly affect TMAO production, as they convert dietary choline and phosphatidylcholine into TMA, which the liver subsequently transforms into TMAO. TMAO activates MAPK and NF-κB pathways, leading to ROS production and inflammation. TMAO also inhibits insulin release, contributing to glucose dysregulation. Bile Acid Modification: Gut microbiota modify bile acids via enzymatic reactions, altering their profiles and impacting lipid and glucose metabolism. The gut microbiota–bile acid axis plays a crucial role, affecting insulin sensitivity, lipid profiles, and gut peptide release. SCFAs: Anaerobic microbes ferment undigested dietary fiber, producing SCFAs (acetate, propionate, and butyrate). SCFAs interact with FFAR2 and FFAR3 receptors, influencing glycolysis, gluconeogenesis, and insulin signaling. They help maintain glucose homeostasis during pregnancy, mitigating insulin resistance. GlcNAc and Metabolic Pathways: Specific pathways activate GLP-1 and promote its secretion indirectly through SCFA production in the intestinal mucosa.