Gut microbiota dysbiosis, circulating microbial genetic traces, and their role in gestational diabetes

Figure 1 Microbiome changes during pregnancy. Typical changes in gut microbiota composition before and during pregnancy. It shows a normal, healthy microbiome with a balance of beneficial bacteria (e.g., Lactobacillus, Bifidobacterium) and a more diverse microbial community, contrasted with a dysbiotic microbiome in pregnant women with gestational diabetes. GDM: Gestational diabetes mellitus.

Figure 2 Microbial translocation and gestational diabetes mellitus. Gut microbiota dysbiosis leads to intestinal barrier dysfunction, allowing microbial components and genetic material to translocate into the circulation. The presence of circulating microbial genetic material can trigger immune activation and metabolic disturbances, thereby contributing to the pathogenesis of gestational diabetes mellitus. GDM: Gestational diabetes mellitus.

Figure 3 Gut microbiota dysbiosis, microbial DNA, and gestational diabetes mellitus. Gut microbiota dysbiosis during pregnancy reduces microbial diversity, weakens intestinal barrier integrity, and facilitates microbial DNA translocation into circulation. Circulating microbial DNA activates immune pathways such as toll-like receptor 9 and cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes, inducing pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-α) that impair insulin signaling. This immune-metabolic disruption promotes insulin resistance, contributing to the pathogenesis of gestational diabetes mellitus and adverse maternal-foetal outcomes. TNF: Tumor necrosis factor; IL: Interleukin; LPS: Lipopolysaccharides; GDM: Gestational diabetes mellitus.

Figure 4 Intergenerational diabetes risk mediated by maternal dysbiosis and microbial DNA. Gut microbiota dysbiosis and microbial DNA in maternal circulation trigger inflammation, leading to placental alterations and impaired nutrient transfer. These processes contribute to foetal programming, thereby increasing susceptibility to obesity and diabetes in the offspring.

Figure 5 Research gaps in the gut microbiota-gestational diabetes mellitus axis. Current evidence links gut microbiota dysbiosis with diabetes during pregnancy. However, the role of circulating microbial DNA as a mechanistic driver of gestational diabetes mellitus remains poorly understood, highlighting a key area for future investigation. GDM: Gestational diabetes mellitus.

Figure 6 Therapeutic implications of the gut microbiota-microbial DNA axis in gestational diabetes mellitus. Gut dysbiosis contributes to impaired barrier function and increased microbial DNA translocation, which may exacerbate gestational diabetes mellitus. Potential therapeutic strategies include probiotics, prebiotics, dietary modulation, and other interventions aimed at restoring microbiota balance, strengthening barrier integrity, and reducing microbial DNA-mediated inflammation. GDM: Gestational diabetes mellitus.