How The Microscopic Residents in the Gut Could Be Critical For a Healthy Pregnancy

The Context: The gut microbiome (the millions of bacterial residents living in the intestines) has a hand in more than you might realize: everything from mental health to immune function. It is also suspected to play a role in prenatal development, but how exactly it does so has not been well understood.

The Study: Pregnant mice with diminished microbiomes have difficulty forming healthy placentas, finds a new study in Science Advances by NYSCF – Robertson Neuroscience Investigator Elaine Hsiao, PhD, of UCLA. Bolstering mice with supplements of short-chain fatty acids (a byproduct of microbiome metabolism) helped them restore placental development.

The Importance: This study illuminates the relationship between the microbiome and fetal development in mice, and this relationship could exist in humans as well. The work could also inform strategies for promoting healthy placental development in pregnant individuals.

“The gut microbiome affects many aspects of host physiology, and more and more evidence is suggesting that it begins to exert its influence even during prenatal life,” said Dr. Hsiao, a UCLA associate professor of microbiology, immunology and molecular genetics in an article from UCLA.

The team decided to investigate whether the microbiome could be affecting development of the placenta – a critical component for delivering essential nutrients and oxygen to a developing fetus.

From Bacteria to Placenta 

They began by observing three groups of female mice: one whose microbiome was wiped out by antibiotics, one that was raised without a microbiome, and one that was raised with a normal microbiome. The mice then mated, and their placentas were studied once they became pregnant.

What the scientists expected was that certain metabolites (products of microbe metabolism in the gut that help with functions like energy) would be depleted in the bloodstream of the placentas. What they found was that they were right, plus a little more.

The team discovered that the placentas of the mice with depleted microbiomes produced smaller placentas with less-developed networks of blood vessels that deliver blood from mother to fetus. The fetuses had lower levels of 27 different metabolites, but also had increased levels of 14 of them.

“This added weight to our initial hypothesis that byproducts made by specific gut bacteria might be acting systemically to regulate feto-placental development and motivated the deeper dive in our study to identify the molecules involved,” said Geoffrey Pronovost, a UCLA doctoral student in Dr. Hsiao’s lab.

The scientists then supplemented the microbiome-deficient mice with the metabolites they were missing. However, this didn’t improve the health of the placenta or the fetus.

Then, the team turned their attention to a different group of metabolites called ‘short-chain fatty acids’ which are involved in metabolism and growth. Short-chain fatty acid supplementation of  microbiome-deficient pregnant mice helped them to grow bigger, healthier placentas that mirrored their microbiome-laden counterparts.

If this connection is present in humans as it is in mice, it could lead to better therapeutic options for those who are pregnant.

“I’m hopeful that these fundamental discoveries in mice could inspire more research that could one day inform new treatment strategies for expectant mothers and their developing babies,” said Dr. Hsiao.

Journal Article:

The maternal microbiome promotes placental development in mice
Geoffrey N Pronovost, Sahil S Telang, Angela S Chen, Elena J L Coley, Helen E Vuong, Drake W Williams, Kristie B Yu, Tomiko K Rendon, Jorge Paramo, Reuben H Kim, Elaine Y Hsiao. 2023. Science Advances. DOI: 10.1126/sciadv.adk1887

Cover image credit: UCLA