Integrative multi-omics analysis reveals probiotic-induced microbiota shifts in women with gestational diabetes.

Introduction: Gestational diabetes mellitus (GDM) is a common pregnancy disorder. It is associated with impaired glucose tolerance and insulin resistance, increasing the potential risks for both maternal and fetal complications. GDM is associated with an increased risk of type 2 diabetes later in life. Management is a big issue in maternal health. New work has underscored the role of the gut microbiota in metabolism and immune function. This indicates that probiotics might exert their mode of action through modulating the microbiota and controlling metabolism. Methods: This study employs a multi-omics strategy to assess the impact of probiotic administration on gut microbiota composition, metabolomic profiles, and host gene expression in GDM women. Women with GDM received probiotics for 8 weeks. Metagenomic sequencing quantified alterations of gut microbiota composition and LC-MS provided untargeted metabolomics in serum and urine. Gene expression was analyzed by qRT-PCR in reference to other physiological factors such as insulin signaling, inflammation, oxidative stress, and gut barrier. Data integration was performed using Principal Component Analysis (PCA), Partial Least Squares Discriminant Analysis (PLS-DA), and network analysis, then pathway enrichment analysis was conducted with KEGG and MetaboAnalyst. Results: The supplementation of probiotics resulted in a significant change of gut microbiota (Lactobacillus 7.6-fold; Bifidobacterium 6.4-fold). Escherichia/Shigella was reduced. The amounts of short-chain fatty acids (SCFAs), especially butyrate and acetate, were increased 3.1 fold and 2.5 fold, respectively. In a gene expression assessment, the insulin receptor and AKT increased 2.5- and 1.9-fold higher, respectively, indicating greater insulin sensitivity. Levels of TNF-α and IL-6 decreased; however, genes related to gut barrier function (ZO-1, CLDN1) increased. Discussion: The administration of probiotic has a great impact on gut microbiome, metabolic activity, and host gene expression in women with GDM. Our data indicate that probiotics may represent a non-invasive and safe treatment for gestational diabetes through enhancing insulin sensitivity, anti-inflammatory environment, and gut health status. Larger confirmatory studies are needed to corroborate these findings and augment future clinical application of probiotics in GDM patients.