Early Immune System Development

The fetal and neonatal (newborn) periods are critical to the development of the immune system and many other biological systems. As the fetus and baby grow, a huge level of adaptation takes place and much of this structural and physiological development is now known to remain with us into adulthood. These changes are driven in part by environmental stimuli, including microbes (bacteria, fungi and viruses).

Here we describe how the baby’s microbiome develops and the factors that influence this development.

Bacteria colonize the baby’s gut

The in utero (womb) environment requires the baby’s immune system to be subdued to tolerate toxins and other challenges experienced from the mother’s body and the changes and stress involved in growth and development.[1] After birth, there is a sudden enormous exposure to environmental toxins, many of them from the mom’s natural intestinal bacteria. This means that the baby’s immune system must adapt quickly to produce immune responses.

Microbes (bacteria) play a critical role in these immune responses and a baby’s microbiome is established immediately at birth when bacteria are transmitted from mother to baby. The first colonization of the gut also occurs at this time, although there is now evidence to suggest that there are low numbers of fetal and placental microbiota prior to birth, thought to be part of the preparation of the baby’s immune system for the outside world.

The newborn gut is a perfect microbial habitat as it contains food, moisture and warmth, which enable the microbes to colonize and start to grow.

How the birth impacts the structure of the microbiome

Research has shown a significant difference between the microbiome of vaginally-delivered and Cesarean-section (C-section) infants. Babies delivered vaginally receive their first colonization of bacteria from the vaginal, skin and rectal bacteria of their mother. 90% of the bacteria present in the baby in the first few days of life has been shown to reflect the vaginal flora of the mom, being mainly Lactobacillus species (primarily Acidophilus strains)

C-section babies acquire bacteria similar to those found on the skin surface[2] and hospital environment. These differences are summarized in the following table:

Bacteria	Vaginal birth	C-section birth
Dominant types	Lactobacilli (mainly Acidophilus types)   Propionibacteria (Staphylococci)   Enterobacteria (various including E. coli)	Staphylococci (S. aureus, MRSA)   Enterococci (E. faecium, E. faecalis)   Enterobacteria
Minor colonizers	Bifidobacteria   Bacteroides   Clostridia	Lactobacilli

For babies born by C-section, a study has shown that swabbing babies with maternal vaginal fluids immediately following delivery can partially restore their gut bacteria to resemble that of vaginally delivered babies. Until this procedure is common practice however, supplementing C-section-born babies with probiotics can help to establish some of the Lactobacillus and Bifidobacterium strains native to the newborn baby’s gut.

Development of the infant gut bacteria​

During the first year of life, the diversity of the bacteria in the baby’s microbiome then increases to drive the development of the immune system and to ensure that the bacteria is recognized by the immune system as ‘self’.[3]

As well as mode of birth, a number of factors have been shown to influence the development of a baby’s microbiome, including breastfeeding[4]^,[5] and antibiotic exposure[6].

Breast milk is a source of a wide range of bacteria for the infant gut and is thought to be specific for each infant. Towards the end of pregnancy, intestinal bacteria are transferred to the mother’s breast tissue during pregnancy in preparation for breast milk production. This ‘mammary microbiota’ development reaches the highest levels at the end the third trimester in preparation for birth. It then remains at relatively constant levels throughout breastfeeding, declines quickly once weaning starts and disappears completely when there is no milk in the mammary gland.

Breast milk has been shown to contain bacteria associated with the gut microbiome[7] and has the ability to affect the development of the baby’s microbiome through:

1. deposition of the mother’s small intestinal bacteria to the baby via breast milk, and
2. stimulation of the large intestinal bacteria by prebiotic fibre (oligosaccharides) present in breast milk

Both colostrum and breast milk contain bacteria and the bacteria present in the gut microbiota of breastfed infants has been shown to reflect that found in their mother’s breast milk.

What can impact the baby’s microbiome?

Giving antibiotics during the first year of life (even briefly) has been shown to alter the constitution of the infant microbiota by depleting the bacterial diversity and its ability to colonize the gut. This change to the development of the microbiota is likely to have long-term implications for health[8], as a higher level of beneficial bacteria is associated with lower levels of atopic disease and obesity in children and adults.

Probiotics have been shown to support the development of the infant gut bacteria[9] and specifically to help reduce the incidence of allergy[10]^,[11]. They may be particularly useful in instances where antibiotics have been required.

What influence does weaning have?

The World Health Organisation recommends that babies are exclusively breastfed for the first six months of life, after which they are slowly weaned onto solid foods that help to meet their increased energy and nutrient needs.

Foods that can help to support the development of the microbiome during weaning include fruits and vegetables for prebiotics and plain yogurt to provide some probiotic bacteria. Continuing to supplement probiotics until the baby is at least a year old can also help with this.

Why supplement with probiotics?​

The composition of breast milk reflects the health and diet of the mother and supplementation of the mother’s diet with probiotics and prebiotics during both pregnancy and lactation may help to optimise this bacterial colonization of the baby’s GI tract.

Providing supplementation directly to the baby may also help to support this and is particularly useful if the infant is formula-fed and is not exposed to the ‘mammary microbes’.

Probiotics in general are considered safe to take during pregnancy and infancy and ProVen Probiotics pregnancy and baby products have been shown to be completely safe in a large clinical trial with more than 450 mother-baby pairs. The moms took the probiotic during the final trimester of their pregnancy and the babies were given the same probiotic blend from birth and for the first six months of life.

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[1] Simon AK et al (2015) Evolution of the immune system in humans from infancy to old age. Proc R Soc B 282:20143085

[2] Dominguez-Bello MG et al (2010), Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. PNAS 107:11971-5

[3] Del Chierico F et al (2015) Phylogenetic and Metabolic Tracking of Gut Microbiota during Perinatal Development. PLOS ONE; DOI:10.1371/journal.pone.0137347

[4] Backhed F et al (2015) Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host Microbe 17:690-703

[5] Tannock GW et al (2013) Comparison of the compositions of the stool microbiotas of infants fed goat milk formula, cow milk-based formula, or breast milk. Appl Environ Microbiol 79:3040-8

[6] Hussey S et al (2012) Parenteral antibiotics reduce bifidobacteria colonization and diversity in neonates. Int J Microbiol; doi: 10/1155/2011/130574

[7] Murphy K et al (2017) The Composition of Human Milk and Infant Faecal Microbiota Over the First Three Months of Life: A Pilot Study. Sci Rep 7; doi: 10.1038/srep40597

[8] Rodriguez JM et al (2015) The composition of the gut microbiota throughout lifeπ, with an emphasis on early life. Microb Ecol Health Dis; 26:26050

[9] Rinne et al (2005) Similar bifidogenic effects of prebiotic-supplemented partially hydrolysed infant formula and breastfeeding on infant gut microbiota. FEMS Immunol Med Microbiol; 43:59-65

[10] Vieira AT et al (2013) The role of probiotics and prebiotics in inducing gut immunity. Front Immunol 4;445

[11] Allen SJ et al (2014) Probiotics in the prevention of eczema: a randomised controlled trial. Arch Dis Child; DOI:10.1136/archdischild-2013-305799