Abstract

Abstract Disclosure: L. Ding: None. J. Liu: None. X. Zhai: None. X. Xiao: None. Background: Gestational diabetes mellitus (GDM) is strongly correlated with considerable risks to both the mother and the developing fetus. Although evidence indicates an association between the altered gut microbiota and GDM, the microbial and metabolic mechanisms that link the metabolic state between mothers and offspring are unknown. This study aims to characterize the maternal and neonatal bacterial and metabolic signatures and their interaction in gestational diabetes mellitus. Methods: Sixty-six mothers (39 women with GDM and 27 normal pregnant women) and eighty-nine newborns (44 from GDM mothers and 45 from normal mothers) were included in this study. Using 16S rRNA gene sequencing and untargeted metabolomic methods, we determined the gut microbiota and serum metabolomics both for mothers and newborns. Results: We found that the microbial and metabolic signatures of GDM mothers and newborns were significantly different from those of the Control group (Ctr), respectively. Intriguingly, we identified 14 genera (Phyllobacterium, etc.) that exhibited identical alterations in mothers and newborns between groups. Among the overlapped differential metabolites in mothers and newborns, 23 (Glutamyl-methionine, etc.) showed consistent alterations between groups, while 19 (Cyclotetradecane, etc.) metabolites exhibited opposite alterations. Metabolic KEGG pathway analysis revealed that 6 pathways, including fatty acid metabolism, sphingolipid metabolism, TCA cycle, transsulfuration pathway, bile acid metabolism, and carnitine metabolism were both enriched in mothers and newborns. Significantly, correlation analysis revealed the notable association between pyroglutamic acid and maternal glucose level in Ctr group was disrupted in GDM group (Ctr: r = -0.46, p = 0.02; GDM: r = 0.04, p = 0.82). Simultaneously, pyroglutamic acid was significantly correlated with neonate serum high-density lipoprotein cholesterol level, which was disrupted in newborns of GDM mothers (Ctr: r = 0.33, p = 0.03; GDM: r = -0.05, p = 0.80). Conclusion: Altogether, we demonstrated that GDM could consistently alter the microbiota and serum metabolome in mothers and newborns, which is significantly associated with their metabolic state respectively. These findings indicate that serum metabolites serve as promising targets to intervene in metabolic transmission in GDM, which needs further validation. Presentation: Thursday, June 15, 2023

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