Dr. dr. Naomi Esthernita F Dewanto Sp.

A(K)
Faculty of Medicine Universitas Pelita Harapan
Education
• Medical doctor : Faculty of Medicine, Tarumanagara University
(1991)
• Pediatrician : Paediatric Department of Cipto Mangunkusumo
Hospital
Faculty of Medicine, University of Indonesia (2000)
• Consultant : Consultant for Perinatology (2008)
• Doctoral : Faculty of Medicine, University of Indonesia (2016)
Position
Lecturer in Faculty of Medicine, Universitas Pelita Harapan
Organization
Member of Indonesian Pediatric Association (2000- now), Member of
Indonesian Neonatology Working Group (2002- now), Member of
Breastfeedng Task force Indonesian Pediatric Society (2014-2017), Head
of Pediatric Department and Nicu coordinator Siloam Hospital Lippo
cikarang hospital (2003- now), Nicu’s coordinator Silaom Hospital Kb.
Jeruk (2010- now), Member of American Breasfeeding Medicine since
2016-now
 Breastfeeding persfective: from womb to world

Antenatal Microbiome,
delivery process, and early
skin to skin
Naomi Esthernita Dewanto
 How does baby microbiome
develop ?

Development of human mammary

microbiota

Disruptors of colonization and Factors influencing

development of neonatal microbiome human milk microbiome
• collection of bacteria, viruses, fungi, and
other organisms that live in and on the
body.

• We have about 10 trillion human cells in our

bodies, and about 100 trillion microbes.

• The balance of microbiomes varies

throughout our body
General composition of maternal and infant
microbiome in pregnancy and early life

Aagaard etal 2016

 Aid digestion, provide
vitamins, regulate the
bowels, stimulate the
development of the
immune system, protect
against infection etc

An imbalance can lead to disease

A balance of microbes leads to optimal

health
 Microbiota of the healthy, breastfed, vaginally delivered,
fullterm infant who remains healthy for a longer follow-up
time is considered the gold standard.

Pediatr Res 2015;72:182-8

How does a baby’s microbiome
develop?
Nat Rev Gastroenterology Hepatology
2012;9:565-76
( Direproduksi dengan izin dari Erika
Isolauri, 2012)
Factor influencing the infant gut microbiota
development
Maternal Geographical
microbiota location
healthy Family environtment
status Breastfeeding vs Diet Diet
lifestyle antibiotic formula lifestyle lifestyle

pregnancy birth infancy adult elderly

Vaginal vs C- Genetics Living

section Comlimentary food environtment
Term vs Preterm Duration of medication
lactation

Window of opportunity for Microbial Modulation Short and Long term health
effects

Microbial Ecology in Health & Disease 2015

 Pregnancy

• The composition of the vaginal microbiota changes throughout

the course of pregnancy
• A woman progress through pregnancy, the bacterial diversity
decreases.
• Specific Lactobacillus sp had higher prevalence during later
gestational agelow pH,preventing ascending bacteria
Development of human mammary microbiota

Fernandez etal 2013

Bacterial translocation

• Mice study: 10% of control (non-pregnant) had

pos MLN culture, 70% of pregnant mice had
bacteria in their MLN’s. Within 24 hours after
delivery, fewer animals had positive MLN
cultures but 80% of mice had viable bacteria in
their mammary tissue

Paediatrics 2007:109:724-32
Transfer of maternal microbiota to mammary gland and
then to breastmilk

Probiotic Placenta &

amniotic
fluid
Type of
Pregnant & lactating birth Neonates
mothers intestinal
lumen

Enterocytes cells of Mammary Breast

Blood flow
intestinal gland milk

Signal activation

Respiratory
Dendritic Mesenteri Thoraci tract
cells c lymph c duct
node
Urinary tract
& genitalia

Salivary &
lacrimal glands
 The effect of Bifidobacterium animalis lactis HNO19
Supplementation among pregnant and lactating
women on interleukin (IL)-8 level in breastmilk and
infant’s gut mucosal integrity
Naomi Esthernita F Dewanto,1 Ali Sungkar,2 Nani Dharmasetiawani,3 Sudigdo
Sastroasmoro,4 Siti Boedina Kresno,5 Rulina Suradi,4 Saptawati Bardosono,6 Dwi
Prasetyo,7 Agus Firmansyah.4
Doctoral Program1 of the Departments of Obstetrics and Gynecology,2 Child Health,4
Clinical Pathology,5 Nutrition6 Faculty of Medicine University of Indonesia, Child Health
Department of Budi Kemuliaan Hospital.3 Child Health Department, Faculty of Medicine,
Padjadjaran University7

• Dewanto etal 2015: probiotic DR10 administered

orally to pregnant and lactating women was
detected in colostrum and in breast milk at 3 months
Result of breastmilk and skin swab
of DR10
DR 10 Probiotic Placebo
n =35 n =35

Breastmilk
n

V0 5 0
V3 7 0
Skin swab

V0 - -
V3 - -

V0: sat birth

V3: at 3 months of age
Delivery
Neonates born by vaginal delivery are exposed to the
mother’s vaginal and intestinal flora as they pass
through the birth canal: E.coli, Staphylococcus,
Streptococcus, Lactobacillus and Bifidobacterium and
produce anaerobic environs in the first few days of life:
Bacteroides & Bifidobacterium spp

J Allergy Clin Immunol 2011;127:1087-94

Infancy
Skin to skin
contact &
Nursing

Environtment &
lifestyle
•Siblings 
colonization ,
Bifidobacterium
maturation of the
spp >>>
infant
• geographical gut microbiome
location
 nothern
europen
Infancy

The babies skin, mouth & digestive tract

are”seeded” by whatever & whomever they
first have contact with
Infancy

Breast milk contains a specific factor that

promotes the growth of Bifidobacterium
bifidum, which rapidly increases in number
with the initiation of breastfeeding.
Colostrum is a transtition from intrauterine to
extrauterine nutrition in all mammals,
including human

Amniotic fluids contain large amount of growth factors

and other protective protein that support the growth,
maturation and protection of the GIT.

Colostrum is more like amniotic fluid than mature milk in

composition,and in support the rapid growth, maturation
and protection of the GIT.
Meier et al,2010
Infancy
• Breastfeeding
Human milk microbiome changes over lactation.
Weisella, Leuconostoc, Staphylococcus, Streptococcus
& Lactococcus : predominant in colostrum
…Infancy
In 1 & 6 months milk: typical inhabitans of the
oral cavity increased significantly ( Veilonella,
Leptotrichia & Prevotella)

Milk from obese mothers tended to contain a

different and less diverse bacterial community
compared with milk from normal weight
mothers.

Am J Clin Nutr 2012;96:544-51

Disruptors of neonatal microbiome
C-Section Antibiotics Formula
feeding
vaginal microbes
at birth (-)  risk of Colonized by
asthma, allergies, skin bacteria
obesity ↑↑
C section

Postnatal Microbiota diversity

colonization of is decreased
neonatal intestine
delayed
Microbiome distribution vaginal delivery vs CS

Dominguez-Bello etal 2010

C-section
• In humans, birth with CS results in alteration
composition of infant gut flora up to at least 6 monts
of age

• Infants born by C-section enter the extrauterine world

ill-prepared compared to vaginally delivered neonates
and are at increased risk for neonatal morbidities:
respiratory distress, hypoglycemia.

• More pronounced humoral immune responses

throughout the first year of lifeT helper 1-type
immune responses reduced during the first 2 yrs of
life

Gut 2014;63:559-66
C-section
• Meta-analysis of 23 epidemiologycal
studies: the risk of asthma is 20% greater in
children born by CS.(Am J Epidemiol 2011;174:1275-85)

• Meta-analysis of epidemiologycal studies:

being born by CS is strongly associated
with increased BMI, overweight and obesity
in adulthood, as well as a 20% increase in
the risk of type1 DM (PLoS ONE 2014;9)
Antibiotics
•before, during, and after
birth also disrupt the natural
microbiome assembly

•decreased bacterial
diversity of the neonate’s
first stool,

•lower abundance of
Antibiotics lactobacilli & bifidobacteria in
the neonatal gut.

•Antibiotics use in early

lifealteration in gut microbiota,
abnormal development of the
immune system.
Antibiotics
• Different antibiotics have specific effects on the gut
microbiota.
• Treatment of mice with combination of amoxicillin,
metronidazole, and bismuthsignificant changes in
overall abundance & community composition of the gut
microbiota.
Withdrawalsignificant recovery towards baseline.
• Cefoperazone ; also resulted in significant disturbance
to the community , withdrawal still depressed in
terms of overall diversity until 6 weeks.

Gut Microbes 2010;1:279-84

Antibiotics and preterm birth

• In preterm: reduced diversity of microbiota, higher level

of potentailly pathogenic bacteria, lower numbers of
Bifidobacterium & Bacteroides compard with full-term.
• Even short term antibioticsignificantly affect the
evolution of microbiota, colonization of Bifidobacterium
disturbed up to 8 weeks, while Proteobacteria are
increased
• Preterm: often + CS & antibiotics
• NEC: linked with microbiota, high level of
Proteobacteria are predictive of the disease

Microbiol Ecology in Health & Disease 2015

Take home messages

The infant microbiome plays an

essential role in human health

• A balance of microbes leads to

optimal health, an imbalance can lead
to disease
The initial development and maturation of the
neonatal microbiome is largely determined by
maternal-offspring exchange of microbiota

• C-section, antibiotics, formula

feeding might become disruptors of
neonatal microbiome.