Babies born by C-section carry an increased risk of immune and metabolic disorders later in life, which studies have suggested may be associated with the communities of microbes on and in their bodies at the time of birth. The diversity of microbes hosted by Cesarean-born babies differs from that of those born by vaginal delivery, a difference that may arise because vaginally born neonates are colonized by microbes as they pass through the birth canal. According to a paper published June 17 in Med, this natural colonization event could be mimicked by swabbing Cesarean-delivered newborns with a gauze soaked with their mothers’ vaginal fluids. The skin and gut bacteria of C-section babies treated with this procedure were more similar to vaginally delivered babies, at least during their first year of life, than those not exposed to vaginal fluids.
A pilot study by Gloria Dominguez-Bello, a microbiologist at Rutgers University and the leader of the current work, had previously shown the potential effects of exposing babies to maternal vaginal fluids. In 2016, her team was able to partially enrich the microbiome of four infants born by C-section using the vaginal gauze procedure. The new study expands those results by increasing the cohort size and extending the time period for monitoring the babies from one month to one year. Anne Hoen, microbial epidemiologist at the Geisel School of Medicine at Dartmouth not involved in the paper, says that it’s this long-term follow-up that really stands out for her.
The current study involved 177 newborns, 101 of whom were from the US while the remaining 76 were from Chile, Spain, and Bolivia. Of the 79 born by C-section, 30 were swabbed with the vaginal fluid–seeded gauze on their lips, face, chest, arms, legs, genitals, anal region, and back.
The feces, oral mucosa, and right arm region of all babies were sampled within the first hours after birth, then between days one and three, every week during the first month, and monthly during the rest of their first year of life. Using 16s RNA sequencing, the researchers determined the bacterial diversity in their stool, mouth, and skin. Throughout the study, swabbed babies—in contrast with those not treated after C-section—showed microbial trajectories that more closely resembled that of vaginally born infants, especially in the skin and feces.
The researchers further measured the seeding effectiveness of different bacterial taxa. They found that the gauze procedure was efficient at providing microbes found in vaginal births, but failed to attenuate the presence of some taxa found only after C-section, which included known opportunistic pathogens.
Treated Cesarean newborns were chosen based on the willingness of their mothers to have them swabbed with the gauze after birth. Thus, “there is the potential for some confounding,” says Hoen, as mothers who “choose to do this procedure may also make other choices or have other exposures that alter their babies’ microbiome as well.” Still, she says that the results provide strong motivation for a randomized trial.
According to Dominguez-Bello, that trial is already underway, with a target number of 600 infants. Babies will be swabbed with either a vaginal or a sham gauze and then monitored during their first three to five years of life. As the health implications of restoring the microbiome are currently unknown, says Dominguez-Bello, the trial will also assess whether doing so could reduce the risks associated with C-section.
Debated microbe origins
While this study is based on the idea that the vagina is the source of a child’s first microbes, that’s still debated. Willem de Vos, a microbiologist at the University of Helsinki and Wageningen University who was not involved in the study but has collaborated with one of the coauthors, says that fecal—not vaginal—microbes are the ones colonizing the infant gut. This new study shows that the vagina could work as “a delivery system of fecal microbes,” he says, but adds that a fecal transplant might be more efficient than exposure to vaginal fluids.
Last year, in a small study of seven infants, de Vos and his colleagues reported that an orally delivered fecal transplant from mothers to newborns could enrich the gut microbiota of Cesarean-born babies to match that of those vaginally born. The fecal transplant also attenuated the presence of pathogens associated with C-section, a goal not achieved in the current study. Dominguez-Bello points out that, while obtaining the vaginal samples for her study, the perineum was also touched, and this is a site that can carry fecal bacteria. Therefore, it is unclear if their failure to achieve attenuation is due to the source of the microbes used or to other factors—for instance, the number of bacteria in the inoculum.
Also, while the gut harbors most of the human microbiome, it’s not the only organ colonized by potentially medically relevant bacteria. The source of the first microbes in other parts of the body is similarly unclear. Dominguez-Bello says the maternal vagina may provide the pioneer colonizers for many different infant organs thanks to what she and her fellow authors refer to as “the pluripotent nature of the perinatal vaginal microbiome” in the paper.
The team found that more than half of the bacterial sequence variants in the vagina on the day of giving birth were also found in other parts of the moms’ bodies. This taxonomic overlap was not found in nonpregnant women from the Human Microbiome Project (HMP) database. If the vaginal microbiome ultimately provides the first microbes for many different body parts, says Dominguez-Bello, it would be logical for the vagina to become more permissible to the colonization of other bodily microbes at the end of pregnancy to facilitate transfers. Though, de Vos cautions that using data from the HMP might bring confounders into the picture, as it ignores any hormonal changes occurring in the bodies of the women in the database, and says that further work is needed to understand the extent of the differences between the microbiome of pregnant and nonpregnant people.