Mother mice’s placental health and the gut microbiome’s role

Naturally occurring bacteria in our guts do more than help us digest food. Researchers have discovered that these tiny organisms also affect our immune system, mental health, and even the growth of a healthy placenta during pregnancy.

Recent research led by UCLA researchers, published in the journal Science Advances, found that mice with fewer gut bacteria had smaller placentas than regular mice. Additionally, the network of blood vessels connecting the placenta and the fetus was less developed in these mice. This study highlights how our gut microbiome can influence various aspects of our health, including pregnancy.

Two conditions, malnutrition, and a diminished gut microbiome, can harm a growing fetus by depriving it of necessary nutrients and oxygen. However, according to researchers, when pregnant mice with these issues were given short-chain fatty acids produced by gut microbes, their placentas grew to a healthy size.

These findings support the idea that the gut microbiome has a role in forming new blood vessels, a process called angiogenesis. They also highlight how metabolites, which are products of microbe metabolism, are essential for the development of the fetus and placenta.

Senior author Elaine Hsiao, a UCLA associate professor of microbiology, immunology, and molecular genetics, said, “The gut microbiome affects many aspects of host physiology, and more and more evidence suggests that it begins to exert its influence even during prenatal life.”

This new research builds on previous work that showed how the gut microbiome affects the development of a baby’s nervous system. While we know that the gut microbiome also influences human fetal development, we don’t need to understand how it works thoroughly.

To figure out how the bacteria in the gut affect something as distant as a developing baby, a team led by Geoffrey Pronovost, a UCLA doctoral student, studied two groups of female mice. One group had no gut bacteria, and the other group had their gut bacteria reduced with antibiotics. They then mated these mice with male mice to study placental development.

Pronovost and Hsiao believed that microbial substances in the bloodstream might be the missing piece of the puzzle.

Compared to mice with normal gut bacteria, those without a proper gut microbiome had smaller placentas with less-developed networks of blood vessels that help transfer blood between the mother and fetus. But the impact of the maternal microbiome goes beyond just blood vessels. Fetuses from mothers with depleted microbiomes had lower levels of 27 substances and higher levels of 14 in their blood.

This supported the idea that substances produced by specific gut bacteria might be influencing the development of the fetus and placenta. To explore this further, the researchers looked for the specific molecules involved.

They initially thought some of these substances might be responsible, but injecting them into mice didn’t improve placental or fetal growth. So, they shifted their focus to another group of substances called short-chain fatty acids, produced when gut bacteria ferment carbohydrates. These acids have various roles in metabolism and growth.

When they gave mothers with depleted gut bacteria an exceptional drink containing these fatty acids, their placentas grew to a size similar to those in the control group. These fatty acids also helped placentas grow in undernourished pregnant mice on a low-protein diet with fewer gut bacteria.

While there are differences between mouse and human pregnancies, the researchers believe similar effects could be discovered in humans.

“I’m hopeful that these important findings in mice could inspire more research that might one day lead to new treatments for pregnant women and their developing babies,” said Hsiao.

This research was supported by the National Institutes of Health and the New York Stem Cell Foundation funding.

Journal Reference:

Geoffrey N. Pronovost, Kristie B. Yu., et al. The maternal microbiome promotes placental development in mice. Science Advances. DOI: 10.1126/sciadv.adk1887.

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