Gut Microbiota in Gestational Diabetes: Modulatory Role in Metformin Therapy and Neonatal Outcomes

Insulin resistance and metabolic dysregulation during pregnancy are the hallmarks of gestational diabetes mellitus (GDM), which is frequently accompanied by changes in the gut microbiota. According to new research, the first-line antidiabetic medication metformin influences the metabolic outcomes of mothers and newborns via modulating the gut flora. The present understanding of the reciprocal link between GDM, gut microbial makeup, and metformin therapy is summarized in this review. Improved glucose homeostasis, intestinal barrier integrity, and decreased systemic inflammation are all facilitated by metformin-induced enrichment of beneficial taxa such as Akkermansia, Lactobacillus, Bifidobacterium, and short-chain fatty acid (SCFA)-producing families (Lachnospiraceae, Ruminococcaceae). By mediating host metabolic and immunoregulatory pathways through FXR, TGR5, and AhR signalling, microbial- derived metabolites, such as SCFAs, bile acids, and tryptophan catabolites, collectively reduce insulin resistance and placental inflammation. To guarantee methodological transparency and the inclusion of high-caliber, current studies, a structured literature selection approach (PubMed, Scopus, Web of Science) was used. Notably, host genetics, diet, and metformin dosage all have an impact on inter-study variability in microbiota response and clinical outcomes, which calls for careful interpretation. Longitudinal and mechanistic research are required to elucidate causal relationships and long-term neonatal effects, even if preclinical and emerging clinical data show microbiota-mediated benefits. Overall, a promising treatment avenue for improving maternal metabolic health and newborn outcomes in GDM is the regulation of the gut microbiota by metformin.