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.

Helminths may influence fecundity rates in women

We’ve often discussed helminths and their impact on human health, and researchers have recently provided more insight as to how these infective parasites can influence female reproductive health.  The immune system plays an important role in fecundity in women.  Shifts in immune responses in regulation are dynamic and these changes can have influence on pregnancy.  Helminths are known to induce marked immunological changes and they infect 500 to 800 million people worldwide.  In addition to modulating systemic immune responses, helminths are also known to directly infect reproductive organs or even the fetus.  While studied extensively in animal models, there is little known as to how helminths influence reproductive processes in humans.  A conglomerate group of scientists sought investigate how helminth infection could affect fecundity rates in women, hypothesizing that helminth infection during pregnancy may increase fecundity because the helminth-mediated immunologic responses may in fact modulate those that impair fertility. 

The researchers collected 9 years-worth of health data from 986 Bolivian women who were forager-horticulturists residing in the Amazonian lowlands of the country.  Western medicine and contraceptives are not used in this region, and it is estimated that different types of helminths infect up to 70% of the population.  Cox proportional hazards model first determined that there was an association between helminth infection and birth spacing.  Next, it was shown that women infected with hookworm were associated with a delayed age of first pregnancy.  Interestingly, and in contrast to hookworm, roundworm infection was associated with early first births (in comparison to hookworm) and shortened interbirth intervals.  The researchers postulated that these differences in associations could be explained by each respective helminth species unique effect on the immune system modulation.  Specifically, roundworm infection is associated with regulatory T cell (Treg) Type 2 immune activation, while hookworm infections are associated with mixed Treg immune activation (e.g. both Type 1 and Type 2 activation).  The association with the specific immune response could also explain why roundworm association was shown to be more favorable to conception, as Treg Type 2 activation more closely resembles pregnancy immune system activity while a Type1/Type2 mix more closely resembles an inflammatory response. 

From a broad viewpoint, these findings are interesting as they point to a species-host interaction that may have an underlying - and underappreciated - influence on demographic/population distribution.  The study of helminths is deserving of more attention, as we continue to acquire a wealth of information from their interactions with humans and implications on human health.  

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 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.  

The gut microbiome shift during pregnancy is related to the mother’s secretor status

Fucose chemical structure

An estimated 20% of women of European descent are not able to produce mucous that have fucose sugars attached to the ends of their mucin molecules.  These women are called ‘non-secretors’, as opposed to ‘secretors’ who can fucosylate their mucins.  This rather peculiar genetic anomaly is not appreciated until it is looked at under the lens of the microbiome.  Many of the microbiota in the gut feed off the host’s mucins for energy, and the lack of fucose is a major factor in dictating which communities can survive in their guts.  During pregnancy the mother’s gut microbiota undergoes a dramatic shift, although what variables are important in determining this shift remain unknown.  Last week though, researchers from Finland showed that secretor status was an important indicator in how a women’s gut microbiome shifts during pregnancy.  They published their results in PLoS ONE.

The researchers sampled the gut microbiome of 71 women throughout their pregnancy, and compared it to the secretor status, as determined by genetic testing.  In the first trimester of pregnancy each women, secretors and non-secretors alike, had similar diversities in their gut microbiota.  However, by the third trimester the non-secretor’s gut microbiomes were much lower than their secretor counterparts.  When the scientists measured specific phyla, they observed an increase in the abundance of Actinobacteria in the secreting women, and an increase In the abundance of Proteobacter in the non-secretors.

The changes in gut microbiota in these women may be very important to the microbiome of the infant that is born to them.  As an infant passes through the birth canal he or she is exposed to the mothers’ vaginal and gut microbiota, and these bacteria serve as the initial populations that seed the infants’ own guts.  In addition, some of these specific bacterial populations, such as Proteobacter, are implicated in diseases like IBD.  If these bacteria persist in the mother after birth they may explain the onset or increased risk of some of these diseases.

Antibiotic exposure during pregnancy may increase risk of obesity in children

We’ve talked a lot about the importance of a woman's microbiome during pregnancy.  Microbiota transfer from the mother to the fetus is critical toward development, having potential downstream health implications for the child.  Researchers in Denmark have recently pointed to the significance of the maternal microbiome with respective to risk of developing obesity during childhood.  Specifically, prenatal infection and neonatal antibiotic use are both associated with childhood obesity.  Researchers wanted to explore further and determine whether or not antibiotic administration prenatally is associated with childhood obesity.  

9,886 Danish children between the ages of 7 and 16 years old were analyzed over 10 years, and information was collected from routine school anthropometric evaluations.  To determine which of the children were exposed to antibiotics prenatally, prescription dispensations and infection-related hospital admissions information was collected from the mothers’ of the children.  Of all the children assessed, 3,280 – or 33% - were exposed to antibiotics prenatally. 

Among all 9,886 children, 768 (7.8%) were overweight as determined by body-mass index ratios.  Increase overweight incidence was correlated to antibiotic use during the second and third trimester.  309 (3.1%) children were considered obese.  Children with obesity were associated with increases in the number of antibiotic prescriptions for the mother.  Overall, antibiotic exposure prenatally was associated with a 26-29% increase in prevalence of both overweight and obesity in childhood. 

These findings point to an interesting relationship that deserves further exploration.  As mentioned, antibiotics have been shown to disrupt microbiome transfer from mother to fetus.  In addition, microbe-associated molecular patterns in development have been shown to be disrupted by antimicrobials.  These agents could also possibly disrupt endocrine and metabolic systems, leading to impaired energy homeostasis and metabolism, and consequently downstream weight issues. 

Obesity is becoming a major health concern for the global population.  Elucidating more information on the molecular underpinnings of the association between antibiotic use and prenatal development could help reveal more information, and perhaps create awareness of maternal antibiotic intake during pregnancy and/or encourage therapeutic intervention in children with obesity.