Dynamic involvement of the core gut microbiome XNP_Guild1 in the evolution of gestational diabetes mellitus

Integrated large-scale maternal microbiome cohort analyses are critical for understanding the development of gestational diabetes mellitus (GDM) and its impact on maternal and offspring health. Here, we analyzed the microbiomes of 2,717 mothers and infants from 9 global cohorts, including both public datasets and a prospective cohort in China, using high-throughput sequencing and multilayer network modeling. We systematically identified and characterized a group of "predicted grey zone" individuals whose gut microbial network features fell between those of healthy and GDM subjects, which represent dynamic ecological transition states in disease development. Notably, we identified and validated across cohorts a core gut microbial guild (XNP_Guild1) that remained highly stable and functionally cohesive across healthy, grey zone, and GDM states, and was significantly associated with both disease progression and early pregnancy risk. In an exploratory intergenerational network analysis, we estimated the vertical transmission effect of the core guild and its potential influence on neonatal growth outcomes. These findings highlight the tight interconnection among core functional gut microbes, transitional ecological states, disease evolution, and maternal-infant health, providing a foundation for future targeted interventions and mechanistic studies of the maternal-offspring microecosystem in GDM.