Bacteria in the mother’s digestive tract appear to stimulate placental blood vessel development, suggests a mouse study funded by the National Institutes of Health. In a series of experiments, the researchers showed that female mice deprived of digestive tract bacteria produced fetuses with undersized placentas that had underdeveloped blood vessels. Similarly, when treated with metabolites—byproducts produced when bacteria feed on carbohydrates in the digestive tract—laboratory cultures of human placental cells produced cell networks similar to blood vessels at an early stage. The authors conclude that studying the relationship between the maternal microbiome and placental development may provide important insights into fetal and maternal health.
The study was conducted by Jeffrey N. Pronovost, a doctoral student at UCLA, and colleagues. Appears in Scientific progress. NIH funding was provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development.
Previous studies in mice have found links between the mother’s microbiome and the development of macrophages (a type of immune cell) in the fetal brain and the development of the fetal nervous system.
For the current study, the researchers sought to determine whether the microbes that colonize the digestive system of female mice could affect the development of the placenta during pregnancy. They set up a series of experiments comparing placental development in mouse fetuses with intact microbiomes to those without.
Mice without a gut microbiome had fetuses with placentas that weighed less than fetuses of mice with intact microbiomes. Further investigation revealed that the placentas from the microbiome-deprived mice were not only smaller, but also had less volume in the placental labyrinth—the series of blood vessels and cavities where maternal blood collects to supply the fetus with nutrients. substances and oxygen. Similarly, fetuses of mice deprived of microbiomes were smaller than fetuses of mice with intact microbiomes.
Placentas from the microbiome-deprived mice also had fewer blood vessels and fewer blood vessel branches. The researchers theorized that substances produced by organisms in the microbiome could influence the development of placental blood vessels. A previous study found that bacteria in the maternal microbiome produced short-chain fatty acids (SCFAs) after carbohydrate feeding and that fewer short-chain fatty acids were present in the circulation of fetuses of microbiome-deprived mice compared to mice with intact microbiomes. The researchers added SCFAs to the drinking water of microbiome-deficient mice and found an increase in SCFAs in the blood of their fetuses. Compared to untreated mice, placentas from treated mice were heavier, had more blood vessels and larger placental labyrinths with greater blood flow.
Previous research suggests that SCFAs promote the health of cells lining the inside of the aorta, the main artery supplying blood to the body. Another found that SCFAs bind to a receptor in fibrous tissue to promote the development of new blood vessels. In the current study, researchers found that treating cultures of human cells from the lining of the umbilical cord vein (a major blood vessel in the placenta) with the SCFAs acetate and propionate promoted the development of blood vessel-like cell networks at an early stage. They then treated umbilical cord cells lacking SCFA receptors with acetate and propionate. Without the receptors, blood vessels failed to generate, suggesting that SCFAs may play a direct role in the development of blood vessels in placental tissue.
The results of the study show that in mice, metabolites of the maternal microbiome play an important role in the development and formation of blood vessels of the placenta. These findings may have implications for conditions affecting the placenta, such as preeclampsia, hypertensive disorder of pregnancy. The authors note that a previous study found that patients with preeclampsia had reduced acetate concentrations.
The authors called for further studies to better understand the role that SCFAs may play in placental development and whether different types of carbohydrates may have different impacts on this development.
Pronovost GN, et al. Maternal microbiome promotes placental development in mice. Scientific progress. 2023