Comparison of blood microbiome between gestational diabetes patients and healthy individuals

Emerging evidence links dysbiosis in gut microbiota with metabolic irregularities in gestational diabetes mellitus (GDM). However, alterations in blood microbiome of GDM individuals remain unexplored. Blood has traditionally been regarded as a sterile compartment, yet emerging evidence of a circulating microbiome raises the possibility that it also contributes to metabolic disease. This study aims to characterize, for the first time, the blood microbiome of women with gestational diabetes mellitus (GDM) relative to healthy pregnant women using 16 S rRNA sequencing, and to determine whether microbial diversity, taxonomic composition, and predicted functional pathways differ between the two groups, thereby clarifying the potential relevance of the blood microbiome to GDM pathogenesis and biomarker development. In this case-control study, bacterial DNA was extracted from blood samples of 40 GDM patients and 40 healthy pregnant women controls. The V2, V3, V5, V6, and V8 hypervariable regions of the 16 S rRNA gene were amplified using a multiplex (5R) sequencing strategy and sequenced on an Illumina MiSeq platform. α and β diversity indices were used to compare microbial diversity between groups, linear discriminant analysis effect size (LEfSe) was used to identify differentially abundant taxa, and PICRUSt-based Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway predictions were performed to explore potential functional differences. The α diversity, as indicated by the Shannon index, exhibited a noteworthy reduction within the GDM group. We observed notable differences in β-diversity between the cohorts. The GDM group’s blood microbiome was characterized by a significant enrichment of the Nocardioidaceae and Planococcaceae families. Conversely, the microbiome of healthy pregnant controls was significantly enriched with bacteria belonging to the order Enterobacterales, notably the genus Escherichia . Furthermore, functional analysis brought to light substantial differences in 30 pathways between the two groups. Specifically, pathways linked to GDM, such as fatty acid metabolism, propionate metabolism, butyrate metabolism, and several amino acid metabolism pathways (including histidine metabolism, lysine degradation, and tryptophan metabolism), compared to their healthy counterparts were upregulated in the GDM group. In contrast, pathways associated with electron transfer carriers, transcription factors, RNA transport, the phosphotransferase system (PTS), transcriptional regulation proteins, as well as carbohydrate digestion and absorption, compared to their healthy counterparts were markedly downregulated in individuals with GDM. GDM is associated with a distinct blood microbial signature, characterized by reduced α diversity, altered β diversity, and specific taxonomic and predicted functional differences relative to healthy pregnancy. These findings suggest that circulating bacterial DNA signatures may hold promise as candidate biomarkers for GDM and warrant validation in larger, longitudinal studies incorporating direct microbiological and metabolic measurements. This study has been registered in the National Medical Research Registration and Filing Information System, with the registration number MR3324015166 (20231126).