1. Caesarean section delivery disrupts the normal pattern of microbial colonization in infants, dominating their gut with bacteria from the human skin and oral cavity rather than vaginal and enteric bacteria acquired during a vaginal birth. 2. Microbial dysbiosis resulting from C-section delivery has been associated with increased risk of conditions like asthma, obesity, food allergies, and inflammatory bowel disease later in life. 3. Restoring a healthy gut microbiota in infants born by C-section through breastfeeding and probiotic supplementation may help reduce the risk of these long-term health issues, though more research is still needed.

1. DYSBIOSIS IN
CHILDREN BORN
BY C-SECTION
Murtaza Kamal
MD (Peds), DNB (Peds), DNB SS (Peds Cardio)
Principal Consultant Pediatric Cardiology & Pediatrics
R & R Hospital and Kamal Hospital
Jhunjhunun, Rajasthan
Feb 16, 2021
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2. Need of the talk…
NFHS-4 says C-section rates have increased from 8.5% to 17.2% from
2005-06 to 2015-16
CDC, 2017: > 30%
Steep rise in CS delivery rates makes it imperative to understand the
potential of microbiota modulation for treatment of dysbiosis
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3. Purpose of the talk…
To present the current understanding of both:
Microbial risk factors that increases the likelihood of a C-section delivery
and
Microbial dysbiosis that is thought to result from C-section
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4. Introduction…
Gut microbiota plays a critical role in infant immune and metabolic
development
Mode of delivery: Major determinant of early life exposure and colonisation
In utero: GI tract essentially uncolonised, so exposure to microbes during
delivery and to the environment immediately following birth is key to
establishment of microbiota
Vaginally derived infants colonised with microbes: Lactobacillus, Prevotella,
Bacteroides, Escherichia/ Shigella and Bifidobacterium (identified from vaginal
and feacal samples from adult mothers)
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5. C-section and microbes
Microbial dysbiosis during pregnancy often associated with complications
that can indicate C-section delivery such as pre term birth, extremes of
maternal BMI, infection, extremes of infant size and gestational diabetes
Birth via CS interrupts the normal pattern of microbial colonisation; no
longer exposed to maternal vaginal or enteric microbes during birth—>
Dominated by human skin and oral bacteria including staph, strept,
corynebacterium, veillonella and propionibacterium
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6. Gut microbiota and diseases
Gut microbiota is intimately associated with training the innate immune
system—> Its disruption in early life can result in infections, sepsis and
systemic immune and metabolic disorders, which influence lifelong disease
risk
Microbial dysbiosis caused by Caesarean-section delivery has been
associated with an increased risk of conditions such as asthma, obesity, food
allergies, type 1 diabetes, systemic connective tissue disorders, juvenile
arthritis, inflammatory bowel disease (IBD), and leukemia
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7. Maternal microbiome during
pregnancy
Maternal microbiome is affected by antibiotic treatment, periodontal disease
and smoking status and has been tied to adverse pregnancy outcomes
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8. Causes of CS and confounding factors
Complications that can indicate CS delivery such as preterm birth, extremes
of maternal BMI, infections, extremes of infant size and gestational diabetes
are often associated with microbial dysbiosis during pregnancy
These indications for CS may themselves have an impact on the microbiota
and therefore confound our understanding of the microbiota in CS delivery
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9. 9

10. Preterm birth as a special case
Preterm neonates more likely to be delivered by CS: Reducing their exposure to
maternal vaginal + enteric microbes—> Resulting in differential immune system
development, which can shape microbial colonisation in their already immature
guts
Subject to higher rates of formula feeding, invasive procedures, antibiotics and
other medications that alter GI pH: Contributing to the altered assembly of
microbial community
Long NICU stays: Antibiotic resistance genes
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11. Preterm birth as a special case
cont…
No single cause of preterm birth identified: Risk factors involves microbial
dysbiosis, including ascending UG infections, descending periodontal
infections and abnormal vaginal microbiota
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12. Other confounding conditions
Other conditions resulting in increased rates of CS delivery: Extremes of
maternal BMI, infections, gestational diabetes and infant size
High maternal BMI is not solely attributable to genetic factors but also
microbial composition
Gut microbial dysbiosis can affect nutrient absorption, inflammation and
microbial translocations well as fetal gut colonisation and development of
fatal metabolic tissues
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13. C- section and long term health outcomes
Immune and metabolic health
GI outcomes
Risk of atopy and allergic diseases
Metabolic syndrome
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14. 1. Immune & Metabolic health
CS delivered infants have increased incidence of T1D, IBD and
autoimmune/ allergic conditions
Literature has evidence in form of multiple studies which imply that early life
events may dictate immune abnormalities that increase risk for diseases
later in life
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15. 2. GIT outcomes
Antibiotics widely used during pregnancy and prior to and immediately preceding CS
delivery to prevent infections
Non culture based studies of adult intestinal microbiome show that antibiotic
exposure may purturb the GI tract microbiota for years
Microbial perturbations in GIT have been associated with Crohn’s disease
In a Danish study of 8,142 IBD people diagnosed before 36 years of age, controlling
for genetic disposition, major factor was CS delivery. Furthermore, majority of IBD
diagnosis occurred after the age of 15, implying that dysbiosis from CS delivery at
the beginning of life may have lifelong health implications
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16. 3. Risk of atopy & allergic diseases
CS shown to increase food allergy
An infant’s odds of developing allergy is influenced by feeding mode (BF/
FF), which represents the first nutrition related microbes entering into the
human body
Feeding mode therefore plays an important role in exposure to and
response to food allergens in early development
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17. 4. Metabolic syndrome
Maternal BMI may be a determinant of infant gut microbial community over
lactation
Breast milk from obese mothers tends to contain a distinct and less diverse
microbial community compared with milk from normal weight women
Breast milk microbiota also differs b/w mothers who delivers by CS vs vaginally,
which could be due to surgery or physiological stress or hormonal signals
Northern Manhattan mothers and children study followed 436 mom-child diads
until 7 year; showed that children exposed to antibiotics during 2nd or 3rd
trimesters had 84% higher risk of obesity
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18. Microbiota restoration therapies for infants
A perturbed infant gut microbiota may be returned to a baseline state through
reintroduction of commensal bacteria along with breastfeeding and/ or through
pre/ probiotic formulations
US-FDA yet to approve any pre/ probiotic formulation to treat microbial
dysbiosis caused by CS delivery
Ongoing clinical trial in UK is investigating whether short term daily probiotic
supplementation with Bifidobacterium in breast fed babies born by CS
promotes a healthy focal microbiota that can be maintained with breastfeeding
until 6 months
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19. Microbiota restoration therapies for infants
cont…
US-FDA trials are testing the safety and efficacy of pre/ probiotics that
targets illnesses associated with CS delivery eg: early life supplementation
with Lactobacillus rhamnosus GG in infants at high risk for asthma
Vaginal seeding: New strategy to restore healthy microbiota. Exposing CS
delivered infants to maternal vaginal contents
Results suggest that focal, skin and oral microbiome of seeded infants
more closely resemble those of vaginally delivered than CS delivered
infants
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20. So, Take home message…
Association b/w microbial dysbiosis in infants delivered by CS and long
term health outcomes is a new field of research
Going forward, it will be necessary to elucidate mechanisms involved, such
as metabolic and immune pathways and microbial function, in order to
apply this research to personalised microbiome based therapies
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21. Thank you
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