Abstract
BACKGROUND: The maternal gut microbiota can modulate host physiological homeostasis through metabolites. Maternal reproductive potential hinges on placental angiogenesis and nutrient transport efficiency, directly determining fetal developmental outcomes. However, the specific molecular mechanisms by which microbial metabolites influence reproductive potential remain to be elucidated. This study aimed to clarify the mechanisms by which maternal gut microbiota affects reproductive potential. RESULTS: We initially analyzed the metabolic profiles by untargeted metabolomics and the fecal microbiota by 16S rRNA sequencing in sows with different reproductive potential. Sows with high reproductive potential exhibited elevated plasma arginine and fecal thiamine levels. Meanwhile, Lactococcus was enriched in the feces of sows with high reproductive potential. Subsequently, we evaluated the effects of thiamine (a signature metabolite identified) on maternal reproductive potential, gut microbiota, placental angiogenesis, and nutrient transport capacity using a rat model. The results showed that thiamine supplementation in pregnant rats effectively promoted offspring growth and enhanced transplacental thiamine metabolism. Moreover, thiamine modulated maternal gut microbiota composition, increased the abundance of Prevotellaceae Ga6A1 group and Bacteroidale RF16 group unclassified, and promoted butyrate production. We found that thiamine improved placental function by enhancing thiamine-related metabolic enzymes and acetyl-CoA content. It also promoted the migratory capacity of pTr cells. Importantly, thiamine facilitated placental angiogenesis by activating Notch signal transduction, which in turn initiated the PI3K/AKT signaling cascade. Ultimately, this cascade regulated the efficiency of placental nutrient metabolism and the expression of nutrient transporters. CONCLUSIONS: Cumulatively, the gut microbiota regulates early offspring development through metabolite-mediated host interactions. This study provides new evidence that maternal gut microbiota-derived thiamine activates placental Notch signaling to coordinate angiogenesis and nutrient transport, thereby improving pregnancy outcomes. These findings provide novel perspectives and potential actionable strategies for maternal microbial regulation of maternal-fetal health during gestation.