What happens if you give c-section babies a vaginal microbiome?

Babies born by cesarian section have greater likelihoods of autoimmune diseases during childhood and later in life.  They also have a gut microbiome that resembles their mother’s skin right after birth. On the other hand, babies that are born vaginally have a gut microbiome that resembles their mothers’ vaginas, and are at lower risk for asthma and allergies.  Given the importance of the microbiome on immune development, many scientists believe that there may be a link between mode of delivery, the initial infant gut microbiome, and normal immune development.

One possible method to ensure a baby that is born by c-section is initially colonized by his or her mother’s vaginal microbiome is to swab the mother’s vagina and transfer her microbiome to the baby immediately after birth.  Researchers from New York University performed this exact experiment, and measured the changes that occurred in the gut after this intervention.  They published their results in the journal Nature Medicine.

In the study, 18 women were split into 3 groups: 7 women gave birth naturally, 7 women gave birth by c-section, and 4 women gave birth by c-section but had their vaginal flora transferred to the babies.  This last group of women had their vaginas screened for pathogens shortly before birth.  After the c-section, and within 2 minutes after, gauze was rubbed in the new mothers’ vaginas and then rubbed all over babies’ mouths, faces, and bodies.  The babies’ skin and gut microbiomes were measured and compared to the other two groups.  As expected, the babies born vaginally had microbiomes that resembled their mothers’ vaginas, and the babies born by c-section had microbiomes that resembled their mothers’ skin.  Interestingly, the c-section babies that were inoculated with their mothers’ vaginal microbiomes, had a microbiome that closely resembled their mothers’ vaginas, even after 1 month.  In addition, there were no adverse consequences to the microbiome transfer.

This was a small proof of concept study that successfully showed a vaginal microbiome transfer to c-section babies could properly colonize a newly born infant.  Further studies still need to confirm that the skin microbiome is unhealthy for a c-section baby, but if it is, then these vaginal flora inoculations may become a critical procedure to ensure a healthy immune system for all newborn infants.

Operating room bacteria colonize infants’ guts after C-sections

Newborns are a great study subject in the field of microbiology, because scientists are still discovering how the microbiome develops and what factors affect it. In human infants, it has been proven that vaginal birth exposes infants to bacteria that are different from those received by the mother through C-section. Babies born by vaginal delivery have gut bacteria correlated with vaginal bacteria, while babies born by C-section have gut bacteria correlated with human skin bacteria. For babies born by C-section, the sources of the human skin microbes that are acquired are still unknown.  In a study published by Microbiome, a group of scientists tested the hypothesis that the operating room environment contains human skin bacteria that could be seeding the gut microbiome of C-section born babies.

To test their hypothesis, the researchers collected samples from 11 sites in four operating rooms from three hospitals in New York City, NY and San Juan, PR. Of the 44 operating room samples that were collected, 68% of the samples contained a sufficient number of bacterial DNA samples for sequence analysis. After analyzing the bacteria collected, it was found that all samples contained human skin bacteria, with Staphylococcus and Corynebacterium being the greatest in quantity. Lamps on the operating bed and baby crib showed higher abundances of these bacteria relative to the other sampling sites. The scientists confirmed that the samples collected were more similar to human skin microbiota than other body sites, by comparing the samples to oral, fecal, and vaginal database samples.       

Even though operating rooms are supposed to be spotlessly clean and germ-free, this study shows that there are still dust particles containing human skin, and therefore human skin microbiota, samples. These samples could be from people moving in and out of the operating room during a C-section, or it could come from the people cleaning the OR. Either way, the human skin bacteria in the operating room most-likely are what influences the infant’s developing gut microbiome. 

Vaginal microbiome once again tied to preterm birth

Preterm birth is major global health challenge.  Today, around 11% of all babies are born prior to 37 weeks, and are considered preterm.  Many of the causes of these preterm births are still unknown, but it is thought that around 25% of them may be related to a bacterial infection that comes from somewhere in the mother’s own body, i.e. her microbiome.  Many studies are now linking specific vaginal bacteria to risk of preterm birth, and other studies have even shown a connection between other microbiome sites, such as the gut and oral microbiome.  Unfortunately, studies on the microbiome and preterm birth are extremely difficult to conduct, so there are just not enough to have any sort of scientific consensus on the topic.  Last week though, a very rigorous study out f Stanford University was published in the Proceedings of the National Academy of Sciences that monitored expectant mothers vagina, gut, and oral microbiome throughout the course of her pregnancy and then for one year after.  Among many interesting findings, which are discussed below, the most important one was yet another connection between bacterial vaginosis and preterm birth.

The researchers monitored the vaginal, distal gut, salivary, and tooth/gum microbiomes of 49 women, 15 of which ended up delivering preterm, over the course of their pregnancy and for one year after.  Interestingly, the non-vaginal sites’ microbiomes remained relatively stable over the duration of the pregnancy, and even for the one year after.  The vaginal microbiome, however, did show some differences during and after pregnancy.

As many of our readers already know, a healthy vaginal flora is dominated by Lactobacilli, but around 20% of American women are dominated by other species, such as Gardnerella vaginalis, and have an overall increased vaginal diversity.  These women have what is known as community state type four, or CST4, and these women could be diagnosed with bacterial vaginosis (BV), though the clinical diagnosis is not so specific.  The other community state types, CST1, 2, 3, and 5, are dominated by different strains of Lactobacilli, and are generally regarded as healthy.  This current research showed that many of the women’s vaginal microbiomes actually shifted between various CST’s during pregnancy, most often shifting to and from CST4.  These transitions had no association with preterm birth, though.  After giving birth the vaginal microbiome became more diverse, and had greater abundances in anaerobic bacteria, such as Peptoniphilus, Prevotella, and Anaerococcus.  In addition, this usually coincided with a decrease in Lactobacilli.  Surprisingly, these changes did not seem to relate to mode of delivery (C-section of vaginal).

CST4 has been linked to preterm birth before, and this was reinforced in this study.  The scientists found that the longer a women’s vaginal microbiome was within CST4, the greater risk she had for preterm birth.  In addition, the abundance of Gardnerella and Ureaplasma, specifically, were linked to preterm birth.

This study reinforces what many microbiome scientists already suspect, and that is the importance of the vaginal flora in preterm birth.  It is unclear at this point if manipulating the vaginal flora prior to, or during pregnancy would help prevent preterm birth, but it is certainly worthy of discussion and clinical testing.  If you are reading this and wondering what your vaginal microbiome is, then we recommend you participate in the citizen science project, YourPrivateBiome, to find out.  You can learn more about it by following this link on our site, or just click the link above.

New contraceptive vaginal ring does not increase risk of vaginal infections

The Nuvaring, a type of vaginal ring.

A newly developed contraceptive device that consists of a vaginal ring that is meant to be used for an entire year is currently under development.  As part of this device’s safety trials the scientists who developed the device monitored how it would impact the vaginal microbiome.  The vaginal microbiome is critical to vaginal health, and certain changes to the vaginal flora are associated with bacterial vaginosis (BV), yeast infections, and other vaginal diseases.  Implanting devices will certainly affect the vaginal microbiome, but fortunately, the scientists determined that the device did not increase the likelihood of getting a vaginal microbiome-mediated disease.  They published their results last week in PLoS ONE.

The vaginal microbiomes of 120 women using the device were measured over the course of a year.  There were no significant increase in the rates of BV over the course of the year.  In addition, the levels of Lactobacilli, which are associated with a healthy vagina, and Gardnerella vaginalis, which has been associated with BV, remained relatively unchanged over the course of treatment.  In addition, measurements on the actual surface of the vaginal ring matched the overall vagina quite well in terms of microbial colonization. In both cases, Lactobacilli dominated.

Any fluid or device inserted into the vagina should be considered for its effect on the vaginal microbiome, for example, douching is associated with BV.  Fortunately, this safety study showed that the vaginal ring did not increase rates of disease, so women out there using a vaginal ring for contraception need not be too concerned that their ring is negatively impacting their vaginal health.

New research shows that Bifidobacteria transfer from mother to child

Both natural birth (as opposed to birth by C-section) and breastfeeding are topics that stir up a lot of conversation among mothers and the scientific community. For example, there is the question of whether breastfeeding rather than formula feeding has some specific benefit to an infant’s health. Well, what about the infant’s gut microbial health? A new article published by Applied and Environmental Microbiology takes a look at whether natural birth and breastfeeding coincides with an exchange of bacteria from mother to child.

Four mother and infant pairs were included in the study that was meant to discover whether the mother transfers any bacterial strains to the infant during vaginal birth and breastfeeding. In particular, the scientists were looking at the genus Bifidobacterium because this group has been known to be early colonizers of the infant gut. In addition, this genus has specific ways of digesting a human mother’s milk. Mother-infant pairs 2 and 4 exclusively breastfed, while pairs 1 and 3 supplemented with formula. Milk samples were collected from the mothers and fecal samples were collected from the mothers and children.

After sequencing the bacteria, B. adolescentis, B. angulatum, B. breve, B. dentitum, B. pseudolongum and B. thermacidophilum were found to be common between all of the mother and the infant fecal samples. The scientists then looked to see which bacteria were in both the mother’s milk and the infant’s fecal sample. The results suggest that the milk may be responsible for transferring B. adolescentis, B. angulatum, B. breve, B. longum and B. pseudolongum to the infant. Interestingly, there were also some bifidobacteria strains that were unique to the infant, suggesting that either they went undetected in the mother or that the infant was exposed to this bacteria from somewhere else.

After six months, samples were collected again in order to see how/if the sample compositions change. The scientists found that, especially in the infants, the abundance of bifidobacteria decreases. This is most likely due to changes in diet – less breastfeeding and more formula feeding – and perhaps environmental exposure. All in all, the results of this experiment shows that the infant microbiome might indeed be influenced by a vertical transfer of bacteria from mother to child. With more evidence of this as a possibility, science may begin looking into more complete analyses with larger study sizes.  

Maternal stress can alter the gut microbiome of progeny, possibly affecting brain development

The composition of the vaginal microbiome has been shown to have major health implications for a female’s health as well as the health of a newborn infant.  During birth, microbiota transfer from the mother to the neonate, which eventually go on to colonize the gut of the child.  It has already been shown that disruptions to the vaginal microbiome can impact microbiota colonization in the gut of a neonate, but downstream implications of this have not been thoroughly explored. 

Researcher’s from University of Pennsylvania set out to examine whether maternal stress in mice, and subsequent changes to the vaginal microbiome, could lead to disruptions in the gut microbiome of their progeny.  Expanding upon this, the researchers further investigated whether these disturbances to the gut impaired metabolism.  This transfer of microbiota occurs during a critical time in brain development, which requires a lot of energy and therefore effective metabolism to fuel this process.  The researchers wanted to identify whether or not maternal stress could disrupt the brain development process by way of alterations to microbiome transfer from the mother to its progeny and a subsequent disrupted metabolic process. 

Male C57 mice and female 129S1 mice were used in this study and were bred to form a hybrid F1 generation.  Stress was administered to the female mice using a well-established behavioral paradigm known as the early prenatal stress model.  Pregnant mice assigned to the EPS-stress group were exposed to a series of stressors (8 in total), but pain was not induce nor did these tests directly influence feeding schedule, weight gain, and litter size. 

Animals were then sacrificed and vaginal lavages were collected to examine bacterial composition between stressed (EPS) and non-stressed groups.  Quantitative PCR was used to characterize the microbiomes of the female mice and their offspring.  Lactobacillus, the predominant bacteria populations in the vagina, was significantly disrupted in the EPS group.  There was a reduction in Lactobacillus in the guts of F1 progeny as well.

Colon and plasma metabolic samples were examined in the F1 hybrid generation by extracting fatty acid metabolites using centrifugation.  Analysis showed that metabolic profiles were significantly different between groups.  Namely, of 29 signature metabolites assessed, 6 were increased and 23 were decreased in EPS progeny as compared to the control groups. 

Brain samples of the F1 hybrid generation were collected and amino acid concentrations were analyzed to assess substrate availability in the developing brain.  The F1 offspring from the EPS group displayed significantly less amino acids.  Interestingly, amino acids in a hypothalamic region of the brain were shown to be deregulated, and these concentrations were much lower in males as compared to females. 

It was interesting to see differences in amino acid availability in the hypothalamus between males and females in light of the fact that there are gender biases in neurodevelopmental disorders such as autism spectrum disorder.  Hopefully future studies can elucidate more on the microbiome to see how it relates to human behavior and brain disease.