The maternal microbiome promotes placental development in mice

Abstract

The maternal microbiome is an important regulator of gestational health, but how it affects the placenta as the interface between mother and fetus remains unexplored. Here, we show that the maternal gut microbiota supports placental development in mice. Depletion of the maternal gut microbiota restricts placental growth and impairs feto-placental vascularization. The maternal gut microbiota modulates metabolites in the maternal and fetal circulation. Short-chain fatty acids (SCFAs) stimulate cultured endothelial cell tube formation and prevent abnormalities in placental vascularization in microbiota-deficient mice. Furthermore, in a model of maternal malnutrition, gestational supplementation with SCFAs prevents placental growth restriction and vascular insufficiency. These findings highlight the importance of host-microbial symbioses during pregnancy and reveal that the maternal gut microbiome promotes placental growth and vascularization in mice.

An altered gut microbiome in pre-eclampsia: cause or consequence

“…The maternal gut microbiome seems to also play a role in placental growth and development. This has been shown via animal models with a depleted microbiome, where placental growth was found to be stunted and significantly reduced ( Pronovost et al., 2023 ). This finding coincided with reduced volume and density at the site of maternal-fetal exchange, termed the placental labyrinth, which subsequently reduced fetal-placental vasculature ( Pronovost et al., 2023 ).…”

“…This has been shown via animal models with a depleted microbiome, where placental growth was found to be stunted and significantly reduced ( Pronovost et al., 2023 ). This finding coincided with reduced volume and density at the site of maternal-fetal exchange, termed the placental labyrinth, which subsequently reduced fetal-placental vasculature ( Pronovost et al., 2023 ). Several further animal studies have demonstrated the positive effects that SCFA supplementation has on the developing placenta, including increased placental size, improved spiral arteries, and reduced inflammatory markers ( Jin et al., 2022 ; Pronovost et al., 2023 ).…”

“…This finding coincided with reduced volume and density at the site of maternal-fetal exchange, termed the placental labyrinth, which subsequently reduced fetal-placental vasculature ( Pronovost et al., 2023 ). Several further animal studies have demonstrated the positive effects that SCFA supplementation has on the developing placenta, including increased placental size, improved spiral arteries, and reduced inflammatory markers ( Jin et al., 2022 ; Pronovost et al., 2023 ). This highlights the potential need for appropriate levels of SCFAs, such as butyrate and proprionate, to be maintained across the gestational period.…”

Expression and clinical significance of short-chain fatty acids in patients with intrahepatic cholestasis of pregnancy

“…SCFAs are associated with various pregnancy complications and can impact fetal growth and development in the womb[ 11 - 13 ]. A recent report in Science Advances found that SCFAs produced by the maternal microbiome play a role in supporting normal placental development, and their absence can limit placental growth and damage placental vascularization[ 14 ]. However, the alterations in SCFAs in the maternal blood of patients with ICP and their influence on fetal health remain unclear.…”

Nutrition during pregnancy: Influence on the gut microbiome and fetal development

“…Pregnancy is a unique biological process in which orchestrated hormonal, metabolic and immunological changes promote fetal nourishment and development within the maternal womb. These physiological adaptations interact dynamically with the microbiota resident in the gut, so that maternal hormonal and metabolic changes shape the structure and diversity of the bacterial community, 49,50 and conversely, microbial byproducts modulate pregnancy‐associated processes including placental development 51,52 and feto‐maternal tolerance 53–56 . Indeed, the bidirectional nature of these interactions is evidenced by the increasing amount of research demonstrating the direct link between imbalances of the microbiota and adverse pregnancy outcomes such as preeclampsia, fetal growth restriction, preterm birth, and gestational diabetes (reviewed in 57 ).…”