During pregnancy, the placenta provides a fetus with everything it needs to develop: oxygen, food, waste disposal, and even antibodies from a mother’s immune system. But not microbes. A new study finds the placenta lacks bacteria, reaffirming the idea that babies gain a microbiome at birth.
The idea of a sterile womb has been around for more than a century. But in 2014, a study found the placenta harbors bacteria similar to those in our mouths—suggesting some microbes can pass from the mother’s mouth into her blood, and from there, into the fetus. Since then, scientists have argued over whether bacterial signals from the placenta are real or contaminants. Researchers hope to settle this debate with the largest study yet, an analysis of placentas retrieved from more than 500 women shortly after giving birth. Published today in Nature, the study reports that healthy placentas have no bacteria.
“It’s just about as clear as you could ever ask for,” said Frederic Bushman, a microbiologist at the University of Pennsylvania who was not involved with the study. He says the researchers are “very skillful with the detective work they did of tracking down multiple sources of contamination.”
To identify the weak signals from a potentially small microbial population in the placenta and not any background signals, the researchers used two DNA sequencing methods. One approach targeted parts of genes common to all bacteria. The other approach was broader, stitching together all DNA present and mapping it to specific bacterial and animal species, says co-author Stephen Charnock-Jones, a reproductive biologist at the University of Cambridge in the United Kingdom.
The researchers were careful to include a number of checks. For example, they spiked samples with a pathogenic microbe found in lizards. By including a known amount of a bacterium that wouldn’t be present in humans, the researchers had a yardstick for measuring the abundance of other bacteria. They also compared bacterial signals with what they expected from contamination from sources such as the DNA sequencing kits or the birth process itself. They found that certain microbes are more prevalent when women give birth vaginally rather than by cesarean section, suggesting those bacteria get on the placenta as it’s delivered rather than living there before birth.
After eliminating sources of contamination, the researchers found just one type of bacterium: Streptococcus agalactiae. This strain, occurring in just 5% of the samples, is a sign of an infection and can cause fatal sepsis in newborns. Taken together, the results show there is no microbiome in the placenta unless it is infected, Charnock-Jones says.
The negative result is important because it speaks to the challenges microbiome research is facing, says Eran Elinav, an immunologist and microbiome specialist at the Weizmann Institute of Science in Rehovot, Israel. Microbiome research started out focused on dense microbial communities in the human gut, which is home to trillions of bacteria. However, as researchers look at smaller ecosystems it becomes trickier to distinguish between truly native colonies and contamination. “I really appreciate the effort made by the researchers to use the best available tools that we have today in order to address this very fundamental question,” Elinav says.
But Kjersti Aagaard, a maternal fetal medicine specialist at Baylor College of Medicine and Texas Children’s Hospital in Houston, isn’t swayed by the latest result. Aagaard, who led the 2014 study that found a placental microbiome, says many of the signals the experiment ruled out as “contamination” are actually evidence of the placental microbiome. For example, she disagrees with the researchers’ choice to disregard some microbes found on the placenta just because they overlap with those found in the vagina.
Aagaard is continuing to test ways to detect these bacterial signals and understand the role that microbes could play in the placenta. One hypothesis, she says, is that placental microbes prevent the colonization of the fetus by dangerous bacteria.
Even though Nicola Segata, a computational biologist from the University of Trento in Italy, finds the latest negative results convincing, gathering definitive proof of a sterile womb will be difficult. Collecting the placenta or amniotic fluid after birth offers a window on how a baby’s microbiome might form, whereas methods of direct observation—testing the gut of the fetus itself—would be both unethical and technically challenging.