Limosilactobacillus reuteri and Lactobacillus johnsonii intervention ameliorates gestational diabetes mellitus-associated sex-specific placental nutrient transporter abnormalities: Links with tryptophan metabolism and aryl hydrocarbon receptor signaling.

AIMS: Gestational diabetes mellitus (GDM) is a common pregnancy complication associated with maternal metabolic abnormalities and adverse offspring outcomes. Although GDM is closely linked to gut microbiota dysbiosis, key probiotic strains and underlying mechanisms remain unclear. This study aimed to identify potential probiotics using microbial signals from clinical GDM cases and a mouse model. METHODS: Metagenomic sequencing was performed on fecal samples from normal and GDM pregnant women; a GDM mouse model was then established for candidate probiotic screening. Combined intervention with Limosilactobacillus reuteri and Lactobacillus johnsonii was applied to assess glucose metabolism, inflammation, intestinal barrier, placental structure, nutrient transporter expression and tryptophan metabolism. RESULTS: Metagenomic analysis showed reduced Lactobacillaceae in GDM women, and the two strains were identified as candidates. The intervention improved glycemic control, insulin resistance, inflammation and colon barrier function, and alleviated placental lesions. Placental nutrient transporters exhibited sex-specific disorders that were normalized by probiotics. Maternal plasma 5-hydroxyindoleacetic acid (5-HIAA) was reduced in GDM mice and restored after intervention, correlating with metabolic indices, placental status, fetal growth and aryl hydrocarbon receptor (AhR) signaling. CONCLUSIONS: Combined L. reuteri and L. johnsonii intervention improved GDM-associated maternal metabolic and sex-specific placental abnormalities.