The bidirectional gut microbiota-inflammation axis in gestational diabetes mellitus: pathogenesis, long-term outcomes, and therapeutic perspectives.

Gestational diabetes mellitus (GDM) is a highly prevalent metabolic disorder of pregnancy that carries immediate and long-term health risks for both mothers and their offspring. Emerging evidence implicates maternal gut microbiota dysbiosis as a critical contributor to the onset and progression of GDM, primarily through the induction of chronic low-grade systemic inflammation. This review synthesizes recent advances in understanding the compositional shifts in the maternal gut microbiota-including depletion of short-chain fatty acid-producing taxa such as Bifidobacterium and Faecalibacterium, and enrichment of pro-inflammatory genera-and examines how these changes compromise intestinal barrier integrity, promote microbial metabolite translocation, and subsequently activate innate immune pathways. The resultant elevation of pro-inflammatory cytokines directly impairs insulin signaling, exacerbating insulin resistance and fueling a vicious cycle between dysbiosis and metabolic deterioration. Beyond the peripartum period, this review highlights the emerging concept of transgenerational programming, whereby maternal GDM-associated dysbiosis and inflammation may shape the offspring's microbiome, immune set-point, and metabolic trajectory, predisposing them to later-life metabolic and neurodevelopmental disorders. Finally, we critically evaluate current microbiota-targeted interventions, including probiotics, synbiotics, and dietary modifications, and discuss the sources of heterogeneity in clinical trial outcomes. By integrating these mechanistic and translational insights, this review proposes a conceptual framework for early risk stratification and personalized management of GDM, emphasizing that effective clinical translation requires moving beyond one-size-fits-all probiotic trials toward stratified, microbiome-guided strategies.