Do Cesarean-Born Babies “Miss Out” on Essential Microbes?
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As technologies such as next-generation sequencing (NGS) have evolved over the last decade, so too has our understanding of the human microbiome – the plethora of bacteria, viruses, fungi and other microbes that inhabit the human body. Just as the microbiome composition varies within and between tissues at any given point, it also evolves and changes throughout our lifetime.
Because humans are born “sterile” – that is, without a microbiome – an important question to address is: when and how does a baby acquire its microbiome? “Studies by our team and others have linked microbiome development to health outcomes, including allergies, obesity and inflammatory disease (for example, diabetes and inflammatory bowel disease). It is therefore important to study how the microbiome develops and what factors impact development,” explains Dr. Wouter de Steenhuijsen Piters, a physician and data scientist at the University Medical Center Utrecht in the Netherlands.
Previous research has explored whether delivery method can shape a baby’s microbiome, with evidence suggesting that babies born vaginally have different gut microbes compared to those delivered by a cesarean section. Scientists from the Wellcome Sanger Institute led a collaborative study which discovered that while vaginally-born babies obtain most of their gut bacteria from their mother, babies born via cesarean did not. Instead, these babies carried gut bacteria associated with hospital environments. Data also suggests that whether a baby is breast-fed or formula-fed after birth is an important determinant of the infant gut microbiome composition.
To date, much research has focused on the gut microbiome, but we also carry microbes in other bodily parts, including the respiratory tract, skin and genitalia. How do other microbiomes, beyond the gut, develop during infancy, and what factors might affect their development?
At the University Medical Center Utrecht, de Steenhuijsen Piters’ work focuses primarily on the infant airway microbiome. Aberrations from “normal” development of this microbiome, he says, are related to increased susceptibility to respiratory infections. Like the gut microbiome, the infant airway microbiome can also be shaped by how a baby is delivered or fed.
de Steenhuijsen Piters led a new study published in Cell Host and Microbe, which comprehensively explored how the microbiome develops during the first month of life. The researchers collected skin, breastmilk, nose, throat, fecal and vaginal microbiome samples from 120 Dutch mothers. From their babies, they also gathered skin, nose, saliva and gut microbiome samples two hours after the infant was born, and when they were one day, one week, two weeks and one month old.
Technology Networks interviewed de Steenhuijsen Piters for our Ask the Researcher interview series. We wanted to know: do cesarean-born babies miss out on essential microbes according to the new research? And, what proportion of an infant’s microbiome comes from its mother?
Molly Campbell (MC): Your study aimed to understand how the infant microbiome develops in different part of the body, and how this is influenced by factors such as birth mode, antibiotic use and lack of breastfeeding. Can you summarize your approach for conducting the research?
Wouter de Steenhuijsen Piters (WSP): We conducted a prospective birth cohort study in 120 mother–infant pairs. We sampled multiple body sites from mothers (i.e., vagina, breastmilk, feces, nasopharynx [back of the nose], saliva and skin) as well as their babies (i.e., feces, nasopharynx, saliva and skin).
This enabled us to track microbes between mothers and babies. What makes this study special is the fact that we could sample babies from birth onwards, so the first samples were collected already two hours after birth. Additionally, we collected samples at one day, one week, two weeks and one month after birth.
MC: Your data suggests that, regardless of birth mode, approximately 60% of a baby’s microbiome is derived from its mother. Can you discuss this finding in more detail, and its importance for mothers and their offspring?
WSP: Indeed, we found that the infant microbiomes were each impacted by multiple maternal microbiomes. Using mathematical models, we tried to “mix” maternal microbiomes in different fractions, aiming to end up with the microbiome of their baby. Using this approach, we could explain ~60% of the baby’s microbiome, suggesting the mother is very important in providing their baby with bacterial source communities.
The fact that multiple maternal body sites impact the infant microbiome contributes to the idea that if one of these sources fail to contribute microbes, a child might receive “more” microbes from one of the other sources. This is what we observed for breastmilk microbiota, which has a stronger contribution to the baby’s (fecal) microbiome in infants born by cesarean section.
MC: What about the other ~40% of the infant’s microbiome – do we know where this is derived from?
WSP: No, we don’t in much detail. I believe it would be very interesting to try and understand where this 40% came from. My suggestion would be that it comes from the environment (possibly pets), fathers, siblings or other caregivers.
MC: Are there any situations identified in the study where an infant could “miss out” on essential microbes?
WSP: Considering the gut microbiome, we found that children born by cesarean section lack a bacterium called Bacteroides, which has previously been associated with health outcomes. Our data suggest that this bacterium is not able to colonize the child over longer periods of time, as it lacks other supporting species that it depends on, which are possibly not transmitted from mother to child.
In addition, we know – mostly based on previous studies based on the same birth cohort – that children born by cesarean section have less Corynebacterium and Dolosigranulum in their upper airways, which has been related to an increased number of respiratory infections over the first year of life. The answer is not black-and-white. Babies do not totally miss out on microbes but may receive less quantities of specific bacteria.
“This is a sound and very comprehensive study in which the researchers investigated the pathways of microbial transmission from mother to child after birth. The authors of the study very carefully examined various skin and mucosal niches in 120 mother–child pairs over the first weeks of life. In doing so, they consistently checked at which niches of the child the mother’s microbes accumulate and from which resource niche they originate,” says Professor Christoph Härtel, director of the Pediatric Clinic and Polyclinic, Würzburg University Hospital, Germany, who was not involved in the study.
MC: Are there any limitations or drawbacks to the study that you believe it is important to highlight?
WSP: Strengths of the study include the high number of body sites explored and the longitudinal sampling for infant samples. In addition, we collected samples directly after birth, which is rare in our area of research.
We could have used more advanced sequencing techniques (e.g., metagenomic sequencing) to even better assess microbial transmission. Also including maternal samples over time would have been interesting, to assess maternal microbiome dynamics leading up to and following birth.
MC: What are your next steps in this research space?
WSP: In addition to understanding where the other 40% of the infant’s microbiome is derived from, we aim to follow our cohort for up to five years to see how early microbiome transmission relates to longer term health outcomes (e.g., asthma, wheezing phenotype and lung function).
The appropriate “starter kit”
Professor Debby Bogaert is a physician scientist at the University of Edinburgh and first author of the study. In a press release, she explains how the findings of the study “make sense” from an evolutionary perspective: “Microbiome transfer and development are so important that evolution has ensured that those microbes are transferred one or another way from mother to child.” She adds, “Breastfeeding becomes even more important for children born by cesarean section who do not receive gut and vaginal microbes from their mom.”
“It’s a smart system, and it makes sense from an evolutionary perspective that these types of pathways are redundant to ensure that the child can begin life with the appropriate ‘starter kit,’” de Steenhuijsen Piters concludes.
Dr. Wouter de Steenhuijsen Piters was speaking to Molly Campbell, Senior Science Writer for Technology Networks.