How Cesarean Birth Shapes the Infant Microbiome

Birth is a pivotal moment in the formation of the microbiome, as newborns begin acquiring microbes that help determine early immune, metabolic, and gut development. The infant microbiome is highly dynamic and shaped by many factors, including type of birth, feeding practices, antibiotic use, gestational age, and an infant's wider environment

As research into the infant microbiome develops, researchers are moving away from simply determining which individual microbes are present in the infant gut to investigating how microbial communities develop and interact with a variety of physiological functions that co-develop during early life.

This article explores the latest research on how Cesarean section (C-section) birth affects early microbiome development, how these changes may influence later health, and whether proposed restoration strategies are ready for clinical use.

A different microbial starting point

A baby born through the vaginal canal acquires microbes associated with the mother's fecal and vaginal microbiome. Infants born by C-section, however, have been shown to display gut microbiomes that more closely resemble those found on the mother’s skin surface.

In infants born by C-section, the establishment of beneficial gut bacteria, such as Bifidobacterium, Lactobacillus, and Bacteroides tends to be delayed. “Reduced colonization by beneficial Bifidobacterium is likely to influence how human milk components are metabolized (i.e., human milk oligosaccharides) and how the infant immune system is supported,” Prof. Lindsay Hall, chair of microbiome research at the University of Birmingham and group leader at the Quadram Institute, told Technology Networks.

Other studies have shown higher colonization in the guts of C-section-delivered infants by microbes associated with the hospital environment, including Clostridium, Enterococcus, Enterobacter, and Klebsiella. The presence of certain bacteria belonging to the genus Clostridium is significant because they can be associated with an increased risk of infections.

Epidemiology studies have also linked C-sections with later health risks such as allergy, asthma, and obesity. Hall explained that these links are biologically “plausible” given the microbiome's role in immune and metabolic development. “However, proving a direct causal pathway in humans remains difficult, and many of the studies that have been done to probe this have been undertaken in animal models—which are of course not the same as humans,” she said.

“We still need stronger mechanistic evidence to determine which changes are causal and which are just (bio)markers of other early life exposures.” — Prof. Lindsay Hall.

Birth by C-section does not always result in permanent, irreversible microbiome disturbances. A study published in the journal Science Translational Medicine followed 700 children in the Copenhagen Prospective Studies on Asthma in Childhood2010 cohort. The researchers examined the effects of C-section on gut microbial composition during the infant’s first year of life. They also explored whether gut microbial perturbations resulting from C-section were associated with a risk of developing asthma in the first six years of life.

The researchers found an increased risk of asthma in children born by C-section, but only if their gut microbiota profile at one year of age remained similar to that at birth. This suggests that while C-sections may alter the infant microbiome, increasing the risk of asthma, appropriate maturation of the microbiome may mitigate against this.

In a recent follow-up study, published in Nature Communications, researchers developed a “restoration score” to assess how closely the gut microbiome of infants born by C-section resembled that of infants born vaginally at one year of age.

The findings showed that gut microbiome composition at one week of age predicted the restoration score at one year, suggesting that early microbial patterns may play an important role in shaping later microbiome development. Infants with older siblings had notably higher restoration scores, driven by increased exposure to beneficial bacteria, likely transferred through close household contact. 

The results suggest that microbiome disruption associated with C-section may not be permanent, but could be modified to improve health outcomes.

“One of the common misconceptions is that a C-section birth can permanently change/alter the early life microbiome,” said Hall. “That is not always the case—as these ecosystems continue to develop over months and years and are shaped by many positive factors including feeding, skin-to-skin contact, diet, environment, and avoiding unnecessary antibiotics.”

Seeding, feeding, and supporting microbial development

Several methods have been proposed for restoring C-section-related microbiome disturbances, such as maternal stool and vaginal-based microbial transfer. Researchers at Southern Medical University say that by exposing C-section babies to maternal vaginal fluids—an intervention called vaginal seeding—it may be possible to partially restore missing gut bacteria.

A total of 68 infants born via C-section were randomly administered a gauze soaked in vaginal fluids or a saline gauze immediately after delivery in a triple-blind manner. Neurodevelopment was assessed using the Ages and Stages Questionnaire, and infant fecal samples were collected at days 3, 7, 30, and 42 after birth to compare the gut microbiota and metabolome.

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Newborns born via C-section who received vaginal seeding had more advanced motor and communication skills than other C-section babies six months after birth. The researchers stated that this is a result of upregulation of certain gut metabolites and metabolic pathways in the infants who had vaginal seeding; however, the exact mechanisms underlying the effects of vaginal seeding remain unclear.

“These studies are scientifically interesting and suggest that it may be possible to modify aspects of the infant microbiome after C-section, but we need to be very careful. These approaches must be tested with robust safety screening and governance, particularly because there is a potential risk of transferring harmful microbes,” Hall cautioned.

Further studies with larger sample sizes and longer-term follow-up are needed before vaginal seeding can be implemented in a clinical setting. The American College of Obstetricians and Gynecologists recommends that vaginal seeding not be performed outside of a review-board-approved research study until adequate data regarding the safety and benefit of the process become available.

An alternative to microbial “seeding” may be personalized probiotics. Hall and colleagues have investigated the effects of probiotics and antibiotics on the gut microbiome and resistome in cohorts of babies born prematurely, many by emergency C-section. These infants have an altered microbiome, with low or absent beneficial Bifidobacterium, and are colonized by bacteria that can cause serious infection.

“We have shown that by replacing the missing Bifidobacterium, we can improve serious health complications and even reduce the number of antibiotic-resistant bacteria in the gut,” Hall stated.

Further phenotypic and clinical investigations are still needed to confirm the suitability of customized probiotics for restoring infant microbiomes.

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“It is one thing to show that an intervention changes the microbiome in the first days, weeks, or months of life, but it is much harder to show that this leads to meaningful health benefits years later, and disentangling this from everything else is also tricky,” said Hall.

“These studies are difficult, expensive, and a major undertaking, but they are essential if we want to move from microbiome associations to clear evidence of clinical benefit and transition into the clinic with robust therapies and approaches,” she continued.

Future outlooks for infant microbiome research

Expectant parents may be concerned to hear that microbiome alterations linked to C-sections may be associated with long-term health implications. However, it is important to remember that delivery method is just one factor that can influence the infant microbiome.  

“C-sections can be lifesaving for mothers and babies, and microbiome research should never be used to create guilt or anxiety around birth mode.” — Prof. Lindsay Hall.

Infant microbiomes continue to develop over months and years—a child with a perturbed microbiome at birth may have a microbiome that ends up looking similar to that of a child born vaginally following similar environmental exposure.

Beyond exploring how the infant microbiome changes, researchers are now interested in understanding which microbiome features matter most for short- and long-term health. This includes identifying the specific strains, microbial functions, metabolites, and timing of colonization that are beneficial for healthy development. By understanding this, it may be possible to develop interventions to help restore the microbiomes of at-risk infants.

“Also important is identifying which infants are most likely to benefit from microbiome-based interventions, as not all C-section-born babies will have the same microbiome profile or the same health risks,” Hall explained.

“We really need long-term, well-controlled studies that follow babies from birth into childhood and combine microbiome data with immune, metabolic, and clinical outcomes, as we want to understand what healthy development looks like and how best to support it when needed,” she concluded.