Even before a baby is born a microbial ecosystem takes up residence in the placenta, creating a microbiome that may help shape the newborn’s immune system and perhaps exert influence over premature births. The revelation, based on the genetic profile of hundreds of placentas, provides the most definitive answer to date that the life-sustaining organ, which nourishes the fetus and helps remove waste, is far from sterile.



Although the composition of human microbiota has become increasingly clear with genetic-sequencing technology, little is known about what shapes humans’ early microbial communities and exactly when an infant is first exposed to and colonized by those microorganisms.



A new catalogue of placental critters is thrusting these microbes into the spotlight, fueling questions about how they may help pull the strings for human health before birth and where a mother’s own microorganisms fit into the equation. Led by Kjersti Aagaard, a professor of obstetrics and gynecology at Baylor College of Medicine and Texas Children’s Hospital, and published in the May 21 Science Translational Medicine, her team’s work analyzes the genetic sequences of hundreds of placental microbiomes from preterm and term infants and compares them with an existing inventory of microbiota from nonpregnant women’s skin, airways, vaginas, guts and mouths.



The work provides initial insights into what microorganisms are present in placenta and where they come from. And the placental microbiome’s apparent similarities to the smorgasbord of oral microorganisms also reignites the debate about links between the role of mother’s gum disease and preterm births. For the placenta, this new work maps out “which organisms are present, what they are capable of doing and how the placental community is likely structured,” the authors wrote. (This work does not, however, directly compare an infant’s microbiota with that of the mother.)



Earlier studies already detailed the composition of the amniotic sac, the guts of newborns in the first week of life and infants’ first stools, providing hints that microbiota may be at work before birth. Still, the placental microbiome—including its existence—remained relatively mysterious until the past couple years. “The beauty of this study is that they don’t just do gram-negative stains of the placenta. They look at the types of microbes that are present by looking at their DNA signatures, which is novel,” says Josef Neu, a University of Florida neonatologist whose earlier work found that even before babies have their first meals their stools host a diverse array of microorganisms, suggesting microbes are present and play a role before the baby is born. Neu was not an author on this new study.



Aagaard’s work finds that placental samples of 320 infants actually most closely resembled the milieu of microbes found in the human mouth—not that of the human gut, stool or vagina. So how would those microbes get there? The authors hypothesize that the microbiota from a mother-to-be’s mouth travels by blood into the placenta, upending an earlier theory that suggests microbes in the placenta and amniotic cavity originate in the vagina. “There are lots of clues to biology and development to be unfolded from little nooks and crannies that we haven’t looked at yet, and the placenta certainly has many of those,” Aagaard says. “The biology of pregnancy is certainly important if we are going to understand the health of the next generation,” she adds.



Although prior work has suggested a mother’s periodontal disease may lead to health problems in infants, efforts to treat pregnant women’s gum disease has not reduced premature births. Aagaard says her new research helps elucidate why such interventions did not work. “Even in the first or second trimester [the microbiome] is already well established,” she says. When it comes to dental care for women before pregnancy, “You would really want to be thinking about primary prevention, not secondary treatment,” she says, noting that oral health should be part of standard treatment for women before pregnancy.



In addition to drawing links to maternal oral microbes, this study also catalogued complex ecosystem differences between the placental microbiome of infants born slightly prematurely—around 34 to 37 weeks—and infants born at term. (Preterm births around this time are more common than early births at, say, 27 weeks). “We don’t know if [the differences] trigger preterm births but we do know they are associated with, and are a good predictor of preterm birth,” Aagaard says.



Differences included a higher prevalence of microbes that typically keep yeast in check among the preterm infants. Across the board, the work found that the single most prevalent microbe in the placentas was Escherichia coli—a bacterium strongly associated with sepsis in premature infants. “The metagenomic survey alone can describe the microbial communities present, but clinical context and advanced inference analyses will be required to understand the factors that affect community composition,” the authors noted.



Urinary tract infections early in pregnancy, too, may alter the placental microbiome, the study suggests. It found a difference in microbiome composition among women who had those infections versus those who did not but the study did not answer if the infection itself or the antibiotics used to treat it may have caused the variance. Moreover, it remains unclear how that microbiome change may have impacted fetal health or preterm birth.



Another interesting finding is that regardless of whether infants were born via cesarean section or descended through the birth canal (and passed through the gauntlet of accompanying bacteria), the composition of the placental microbiome appeared to be roughly the same in this analysis, indicating mode of delivery, at least for the placenta, does not alter its microbial community. The finding does not answer how that birth method impacts an actual infant, because a baby would typically swallow amniotic fluid and microbes along the birth canal during delivery.



With the new profile of the placental microbiome, “we do not know what is cause and effect here. That will take a much longer ongoing longtitudinal samples to answer,” Aagaard says. Next up, her team plans to delve further into answering questions including how cesarean section versus natural birth influences infants’ microbiomes.

