Summary: Newborn microbiome differs by mode of delivery and feeding. Newborn C-section microbiome: Swabbing C-section babies partially restores the newborn microbiome.
First, a quick refresher of “How we acquire our gut microbiome.“
Our gut microbiome is acquired at birth, though this is by no means a simple answer. The post “Newborn Gut Microbiome Begins at Birth” details many differences between the newborn gut microbiome due to mode of delivery (vaginal versus C-Section) as well as feeding (breast-fed versus formula-fed). The figure below extends this and shows the recent findings that the developing microbiome is shaped not only by delivery and feeding mode, but that antibiotics, probiotics, and environmental exposures also interact and develops the newborn’s microbiome and resultant immune system.
This table depicts the many functions of the gut microbiome which are metabolic, nutritive, pathogenic protective, and immunologic. Realize that this dynamic virtual organ is only now being truly recognized for the life sustaining roles it serves.
Newborn mode of delivery and early feeding practices are considered “external environmental factors” and both affect the newborn microbiome and resultant immunophysiological conditions.
It can now be said that the effects of delivery mode and infant diet are determinants of the essential microbial community in early life. As summarized in this study: Infants born by cesarean are at increased risk of asthma, obesity and Type 1 diabetes whereas breastfeeding is variably protective against these and other disorders. Health impact for newborns not breast-fed, as detailed in this NCBI article, “The Risks of Not Breastfeeding for Mothers and Infants,” include: increased incidence of otitis media, gastroenteritis, pneumonia, childhood obesity, Type 1 and Type 2 diabetes, leukemia, and sudden infant death syndrome. Lastly multiple studies including this July, 2013 study, as well as this Feb, 2014 study, notes that, “Although the exact mechanisms remain to be elucidated [for the alterations in the gut microbiome that are associated with a variety of disease states], these correlations appear to stem from differences in gut microbial communities.“
The newborn microbiome differs when comparing breast-fed to formula-fed as well as mode of delivery:
Mammals drink maternal milk exclusively for a substantial proportion of their development which further enriches their microbial community. Breast-milk is rich in prebiotics, selects for persistence of beneficial bacteria and limits colonization of harmful ones. The strong selective pressure of breast milk is demonstrated by the lower diversity of microbes in the gut of breastfed infants than in the gut of formula-fed infants.
- Compared with breastfed infants, formula-fed infants had increased richness of species, with over-representation of Clostridium difficile.
- C-Section born infants had underrepresented Escherichia–Shigella and Bacteroides species.
- Infants born by elective cesarean delivery had particularly low bacterial richness and diversity.
The post, “MICROBIRTH” EVERY PARENT NEEDS TO VIEW,” is a must read. Microbirth is a 60 minute documentary that explains: From the changes that occur in the human pregnant vaginal microbiome to that microbiome which actually inoculates the baby, be it via C-section or vagina birth, these events are now showing to have associated consequences for the health of the child and such could have life-long consequences making our children more susceptible to disease later in life:
Recent population studies have shown babies born by Caesarean Section have approximately:
- 20% increased risk of developing asthma,
- 20% increased risk of developing type 1 diabetes,
- 20% increased risk of obesity,
- slightly smaller increases with gastro-intestinal conditions like Crohn’s disease or coeliac disease, and
- These conditions are all linked to the immune system.
This documentary explains that as a consequence of insufficient microbiome seeding due to C-section, the baby’s immune system may not develop to its full potential…“The immune system doesn’t mature, and the metabolism changes. It’s the immune dysfunction and the changes in metabolism that we now know contribute to those diseases and conditions.” -Dr Dietert
- How fully seeded can a child get after a C-section? As a group, C-section delivered babies have a lower diversity of microbes and lower numbers of some useful bacteria types comprising the microbiome than do vaginal-delivered babies. So they are not as fully complete and also their seeded microbiome is less derived from their mother compared with vaginally delivered babies. Treatments such a the use of vaginal swabs at birth for C-section babies may be helpful for self completion.
- And what or whose microbiomes is a C-section child getting? The exact range of sources of the C-section baby’s microbiome remains somewhat uncertain. But it is clear that much less of it is from the mother (particularly for gut microbes) than in vaginally-delivered babies. So for C-section babies, much of their seeding is coming from the surroundings (e.g., the hospital environment, hospital personnel, and patients).
- Are most of the auto-immune diseases coming from C-section born children? As a group, C-section delivered babies have a higher prevalence of auto-immune and allergic conditions than do vaginally delivered babies. However, birth delivery mode is not the only factor in risk of immune disorders. Exposure of the parents (particularly the pregnant mom) and the baby or infant to toxic chemicals (e.g., heavy metal, plasticizers, pesticides, air pollutants) and drugs and/or to adverse environmental conditions (low vitamin D, stress/abuse) can also produce immune dysfunction and elevated risk of auto-immune and allergic diseases.
- Are there children with these listed diseases that were born vaginally? Vaginally-delivered children can and do get auto-immune and allergic diseases. Their families may have genetic predispositions for these diseases and/or they may have exposed either in utero or early childhood to harmful chemicals or drugs that promote these diseases. For example, a mother with extensive heavy metal exposure or who had multiple rounds of antibiotics and delivered vaginally could have a severely depleted microbiome for seeding her baby. However, as a group, vaginally-delivered children have a lower prevalence for these immune disorders than occurs with C-section delivered babies.
- If so, where do their diseases originate? Immune and inflammatory disorders such auto-immune and allergic diseases are thought to originate via a combination of family genetics, prior family-related exposures (epigenetics) and current early life environment. The developing immune system is programmed for dysfunction and as the child matures, improper immune-related responses to environmental challenges (e.g., childhood infections) show up as auto-immune, allergic or inflammatory conditions. Because the microbiome helps to train the immune system as to what is friend or foe, a complete and useful microbiome helps to reduce the risk of these diseases.
Another study noting mode of delivery microbiome differences found: “vaginally delivered infants are more likely colonized by Lactobacilli and Prevotella, whereas infants delivered by C-section more frequently acquire bacteria present on the mother’s skin and in the surrounding hospital environment, such as Staphylococcus, Propionibacterium, and Corynebacterium.”
The vaginal microbiome which inoculates the newborn’s gut during birth is dynamic during pregnancy.
All mammals passing through the vaginal canal are inoculated with the mother’s vaginal bacteria first, before environmental exposure. Indeed, this study shows that the vaginal microbial communities of pregnant women (green) in fact differ from those of nonpregnant women (blue); for example, the genus Lactobacillus johnsonii, (a species of bacteria normally found in the gut) becomes more abundant in pregnancy. This strain is associated with enzymatic activity and thus may prime the newborn gut for digestion. Most remarkable is the dynamic nature of the vaginal metagenome and its role in vertical transmission of the microbiota through subsequent generations.
Lastly, breast milk microbiome changes over lactation time-frame. It also changes based on the mother’s weight status (obesity).
Interestingly, this study showed that:
- Colostrum had predominant Weisella, Leuconostoc, Staphylococcus, Streptococcus, and Lactococcus bacteria,
- 1- and 6-month breast milk samples had significantly increased levels of Veillonella, Leptotrichia, and Prevotella. These bacteria are typical oral cavity inhabitants.
- Milk from obese mothers tended to contain a different and less diverse bacterial community compared with milk from normal-weight mothers.
- Milk samples from elective but not from non-elective (or emergency) Cesarean birthing mothers contained a different bacterial community than did milk samples from individuals giving birth by vaginal delivery. This suggests that it is not the operation per se but rather the absence of physiological stress or hormonal signals that could influence the microbial transmission process to milk.
Putting all the above together, several studies are now ongoing looking to answer:
Can a C-Section microbiome be manipulated at birth to better approximate that of a vaginal birth?
Dr. Maria Gloria Dominquez-Bello from NYU: This study inoculates the C-Section newborn with a gauze that has been inserted in the vaginal canal for one hour prior to Cesarean birth. These infants are then followed for one year to see if their microbiome normalizes. The preliminary data: Four babies at four months seems to have acquired the mother’s vaginal microbiome, and their microbiome is beginning to look more like that of a natural vaginal birth. Dr. Rob Knight of the Knight Labs (studies our microbial landscape via gene sequencing) explains here, “When my own daughter was delivered by emergency c-section, we took things into our own hands and made sure she was coated in vaginal microbes, With one person, you don’t really have enough of a sample size. But she has not had a single ear infection.”
Dr. Maria Gloria Dominquez-Bello: “In other words, if we got one bacteria in the C-section baby that is associated with the vagina, we got two in the inoculated C-section but six in the vaginal births. So those C-section babies still don’t have the full exposure of the vaginal babies.
That’s logical because during labor, the baby is rubbing against the mucosa of the birth canal for a long time and bacteria start growing even before the baby is out — growing and colonizing the baby during birth. In half an hour, you get multiplication of bacteria. If the baby gets one cell, an hour later the baby has probably four of those cells and five hours later, it’s exponential.
Also, C-sections involve antibiotics. There is no C-section without antibiotics, and we don’t know what the effect is of that gram of penicillin. If it’s good enough to kill strep B, I’m sure it’s killing a lot more than that community of bacteria,”
Q: What’s your next step in your research on the gauze intervention?
We’re increasing the number of babies. We already have 12 inoculated and we’re publishing the work on this first little group just to publish the principle that it works as expected: of course, if you expose a baby to an inoculum, you get the inoculum in the baby. It’s a little simple but it’s important to show it works.
And we are doing the study in other countries. We’ve started in Bolivia, we’re going to start it in Ecuador, in Stockholm and here, It’s still going on in Puerto Rico, and Chile has already started. So I hope to have a much bigger number of babies, and so far we’re following them for a year but maybe we’ll extend that. Ideally we’d have a big birth cohort study, and that’s a lot of money. To show the effect directly, to follow up prospectively and to study whether the kids develop asthma or not, that would be awesome but it’s a big study and needs funding. We’re doing this with very little funding. ~From this interview.
Sidenote: An antibiotic prescribed for an ear infection resulted in a huge microbiome hit but the community recovered (unclear if this was for breast-fed or formula-fed infant, or of the mode of delivery).
Dr. Elizabeth Costello of Stanford is looking at what the newborn microbiome looks like at the end of two years comparing vaginal births (bacterial genus called Bacteroids is in abundance) versus Cesarean births (Bacteroids are nearly missing). Questions to be answered are: Do the Bacteroid species decrease for vaginal births, do Bacteroid levels increase for C-Section births, and do the differing birth methods normalize and approach other?
This study is also looking at antibiotic use relative to recovery of the gut microbiome since almost half of the infants have had at least one antibiotic hit. They are looking to learn: Are there reduced numbers of beneficial bacteria and is recolonization to a normal microbial community impeded?
The infant gut is particularly susceptible to alterations of the resident microbiota.
Changes in the developing microbiota have been associated with breastfeeding, cesarean delivery and antibiotic use.
These changes in the developing microbiome could explain susceptibilities to a variety of conditions later in life.
Women and medical professionals should be aware of these issues when planning delivery and neonatal care.
Some side notes for asthma, adult Metabolic Syndrome, and environmental toxins relative to newborn gut microbiome:
Increasingly, more and more later life diseases are being associated with mode of birthing delivery as well as breast-fed versus formula-fed newborn feeding. This October, 2014 study adds increased risk of metabolic syndrome, by about age 45, for emergency C-Section births occurring in 1958. This increased risk of metabolic syndrome adds to the correlative disease list of: obesity (1,255 children born between 1999 to 2002 evaluated at 3 years of age), Type 1 Diabetes, and asthma. The risk of metabolic syndrome is increased for emergency caesarean delivery for a 1958 population after adjusting for prior confounding factors. The researchers hypothesize that emergency caesarean is suggestive of a ‘fetal stress’mechanism affecting health across the life-course, but note that others factors not considered may explain this outcome.
Relative to asthma, this study showed that abnormal development of the intestinal microbiota reported following Cesarean delivery may continue even beyond infancy. 60 Finland seven year olds were randomly selected representing 31 Cesarean and 29 vaginal deliveries for evaluation of antigen specific IgE antibodies. They found that at 7 years of age, the bifidobacterial levels were comparable independent of the mode of delivery at birth, while clostridia were significantly higher in the vaginally born children. Six children diagnosed with asthma all had lower numbers of clostridia in their faecal specimens while the other non-asthma 54 children had higher clostridial numbers. Differences in neonatal gut microbiota, in particular the balance between Bifidobacterium species and Clostridium species, have been reported to precede heightened production of antigen specific IgE antibodies, a hallmark of the atopic responder type.1 Note that this finding does not demonstrate causation, it is only correlative though it is interesting to see the persistence of the microbiome Clostridium skew.
Environmental toxins play a legitimate role in microbiome manipulation. An example is the environmental toxin that could exert pressure on the development of the microbiome is bismuth which is a common exposure in neonatal and infant populations. Bismuth is a common ingredient in cosmetics and medicines such as Pepto-Bismol. A normal gut inhabitant, Methanobrevibacter smithii, transforms bismuth into a form that is toxic to Bacteroides thetaiotaomicron, a beneficial resident that mediates infant dietary transition from breastmilk to starches, and aids the formation of the intestinal mucosal barrier that protects against pathogens . Consequently, microbiome skew would create an opportunity for other bacterial or pathogenic microbes to increase and fill in the ecosystem voids.
It will be interesting to learn the conclusions of the Dominquez-Bello and Costello studies. In the meantime, it seems imperative that parents-to-be are advised of and understand the microbiome risks due to mode of delivery and feeding choices.
Updated results: The article, Scientists swab C-section babies with mothers’ microbes, reports on the first results of swabbed babies. The study can be found at Partial Restoration of the Microbiota of Cesarean-born infants by Vaginal Microbial Transfer. The cohort: 7 vaginal birth infants and 11 C-section birthed infants (4 were swabbed). After 1 month, the 4 C-section infants swabbed had skin, gut, anal, and oral microbiomes more like those vaginal born. In a follow-up study looking at 75 infants after 1 year, Dominquez-Bello says, “After one year, I can tell you how the baby was born with pretty high precision [swab, vaginal, or C-section].” To determine long-term consequences to BMI, allergy, or asthma you would need ~1200 infants and follow would be 3-5years. Last updated: November 3, 2017 at 15:15 pm
In health through awareness,