Human breast milk: A review on its composition and bioactivity

Nicholas J. Andreas1, Beate Kampmann1 3, Kirsty Mehring Le-Doare1 2 3

1Centre for International Child Health, Department of Paediatrics, Imperial College London, St. Mary’s Hospital, Praed Street, London, W2 1NY, UK

2Wellcome Trust Centre for Global Health Research, Norfolk Place, London, UK

3MRC Unit-The Gambia, Vaccines & Immunity Theme, Atlantic Road, Fajara, The Gambia

n.andreas11@imperial.ac.uk

b.kampmann@imperial.ac.uk

k.mehring-le-doare@imperial.ac.uk

Corresponding author: Nicholas J. Andreas, Department of Paediatrics, Imperial College London, St. Mary’s Hospital, Praed Street, London, W2 1NY, UK. Tel.: +44 207594 2063.

Keywords: Human milk, Child Nutrition Science, Neonate, Immunity

Conflicts of interest statement: NJA has received support from Medela and Danone to attend an educational conference, but declared no other conflicts of interest. KLD has received support from the Wellcome Trust and Thrasher Research Fund for her work. BK is funded by the MRC and has received support from other funders, such as the Wellcome Trust, the BMGF and the Thrasher Foundation.

Abbreviations: Group-B streptococcus, GBS; HMO, human milk oligosaccharides; secretory IgA, SIgA;

toll-like receptor, TLR; Transforming growth factor beta, TGF-β;

Acknowledgements: We acknowledge the support of the Imperial College Biomedical Research Centre and the Wellcome Trust for our work. Also, we would like to acknowledge Jessica Birt, Amadou Faal, Asmaa Al-Khalidi, and Mustapha Jaiteh.

Abstract

Breast milk is the perfect nutrition for infants, a result of millions of years of evolution, finely

attuning it to the requirements of the infant. Breast milk contains many complex proteins, lipids and

carbohydrates, the concentrations of which alter dramatically over a single feed, as well as over

lactation, to reflect the infant’s needs.

In addition to providing a source of nutrition for infants, breast milk contains a myriad of biologically

active components. These molecules possess diverse roles, both guiding the development of the

infants immune system and intestinal microbiota.

Orchestrating the development of the microbiota are the human milk oligosaccharides, the synthesis

of which are determined by the maternal genotype. In this review, we discuss the composition of

breast milk and the factors that affect it during the course of the breast feeding.

Understanding of the components of breast milk and their functions will allow for the improvement

of clinical practices, infant feeding and our understanding of immune responses to infection and

vaccination in infants.

Introduction

Breast milk is an extremely complex and highly variable biofluid that has evolved over millennia to

nourish infants and protect them from disease whilst their own immune system matures. The

composition of human breast milk changes in response to many factors, matching the infant’s

requirements according to its age and other characteristics (1, 2). Therefore, the composition of

breast milk is widely believed to be specifically tailored by each mother to precisely reflect the

requirements of her infant (3).

The many antimicrobial and immunomodulatory components of breast milk are suggested to

compensate for the deficiencies in the neonatal immune system, and impair the translocation of

infectious pathogens across the gastrointestinal tract (4). In addition, breastfed infants are also

known to possess a more stable and less diverse intestinal microbiota than formula fed infants, but

possess more than twice the number of bacterial cells (5). This may be partially due to alterations at

the level of the gut mucosa due to bioactive substances in human milk.

Demonstrating the bioactivity of breast milk, a study on shed epithelial cells in the faeces of infants

has shown that gene expression in the neonatal gastrointestinal tract is influenced by breastfeeding,

with differential expression found between formula fed and breast fed infants in genes regulating

intestinal cell proliferation, differentiation and barrier function (6).

Breast milk contains bioactive factors that are capable of inhibiting inflammation, as well as

enhancing specific-antibody production, including the compounds PAF-acetylhydrolase, antioxidants,

interleukins 1, 6, 8, and 10, transforming growth factor (TGF), secretory leukocyte protease

inhibitors (SLPI), and defensin 1 (4). Breast milk also contains factors with the potential to mediate

differentiation and growth of B cells, including high concentrations of intracellular adhesion

molecule 1 and vascular adhesion molecule 1; and lower concentrations of soluble S-selectin, L-

selectin and CD14, (4).

Additionally, pattern-recognition receptors, which are crucial factors in the recognition of

microorganisms in the neonatal respiratory tract and gut, are present in breast milk. Factors such as

the Toll-like receptors (TLR-2 and TLR-4) provide efficient microbial recognition, working in synergy

with the co-receptor CD14 and soluble CD14, which are found in high quantities in breast milk (7).

Further regulation by soluble toll-like receptor 2 (sTLR-2) which regulates cell activation via cell

surface TLR2 has also been noted in breast milk but not in infant formula (8). Similarly, an as yet

unnamed 80kDA protein identified in breast milk appears to inhibit TLR2-mediated but activates TLR-

4 mediated transcriptional responses in human intestinal epithelial and mononuclear cells (9).

Reduced TLR-2 responsiveness at birth has been proposed to facilitate the normal establishment of

beneficial microbiota such as bifidobacteria.

Various studies have examined the influences of maternal characteristics on breast milk

composition. Important factors known to influence breast milk composition–such as the gradual

increase in fat concentrations throughout a feed, have well defined effects. However, other potential

influences, such as the mode of delivery and maternal BMI, have less high quality evidence

supporting their role. The difficulties in accurately assessing the composition of breast milk (e.g.

sampling time) hinder efforts to elucidate the true value of these effects. Furthermore, there is a

profound lack of knowledge regarding how alterations in breast milk composition may subsequently

impact infant and later health outcomes.

Metabonomics, the study of multiple metabolites in biofluids, using techniques including mass

spectrometry and 1H NMR spectroscopy, is capable of measuring components in extremely low

concentrations. This may assist in unravelling the factors influencing breast milk composition, as well

as identifying previously unidentified components and their influence on human health (10, 11).

In this review we discuss the nutritional and non-nutritional components of breast milk and the

effect of breast milk components on infant colonisation with potentially pathogenic bacteria and

factors which are known to influence its composition.

Lipid

Lipids are the largest source of energy in breast milk, contributing 40-55% of the total energy of

breast milk (12). These lipids are present as an emulsion. The vast majority of lipids secreted are

triacylglycerides, contributing towards 98% of the lipid fraction. The remainder predominantly

consists of diacylglycerides, monoacylglycerides, free fatty acids, phospholipids and cholesterol.

These components are packaged into milk fat lipid globules, with the phospholipids forming the bulk

of the membrane of the globules and the triacylglycerols found in the core (13), Figure 1. These

globules usually range from 1-10 µm across, with an average diameter in mature milk of 4µm (14).

Figure 1: An optical microscopy image of milk fat lipid globules, displaying the structure of milk. Adapted with permission from (15), American Chemical Society.

Breast milk contains over 200 fatty acids; however, many of these are present in very low

concentrations, with others dominating, for example oleic acid accounts for 30-40g/100g fat in

breast milk (16). De novo synthesis of fatty acids accounts for approximately 17% of the total fat in

breast milk (17). Long chain polyunsaturated fatty acids, molecules with a chain length of more than

20 carbon atoms-plus 2 or more double bonds, constitute ~2% of the total fatty acids present in

breast milk (18).

The positions occupied by fatty acids along the glycerol backbone are highly conserved, with the

fatty acids commonly appearing in specific positions, Figure 2 (19). For example, fatty acids present

in the highest concentrations in breast milk; oleic, palmitic and linoleic acid, are commonly found at

the sn-1, sn-2 and sn-3 position respectively (19). Interestingly, the distribution of fatty acids along

glycerol influences their availability; with palmitic acid at the sn-2 position being absorbed more

readily. Significantly, this positional preference is not replicated by many artificial formulas, and has

been observed to influence the infants plasma lipid profile, including cholesterol concentration (20).

Figure 2: Structure of triacylglycerol with the sn positions annotated. Adapted with permission

from (21).

Short chain fatty acids (SCFA) found in breast milk are also an important source of energy (22), as

well as being essential for normal maturation of the gastrointestinal tract (23). Sphingomyelins,

present in the milk fat globule membrane, are especially important for central nervous system

myelinisation, and have been shown to improve the neurobehavioral development of low-birth-

weight infants (24).

Breast milk lipids have been shown to inactivate a number of pathogens in vitro, including Group-B

streptococcus (GBS). This suggests that lipids provide additional protection from invasive infections

at the mucosal surface, particularly medium chain monoglycerides (25).

Breast milk protein

Breast milk contains over 400 different proteins which perform a variety of functions; providing

nutrition, possessing antimicrobial and immunomodulatory activities, as well as stimulating the

absorption of nutrients (26, 27). Proteins present in milk can be divided into three groups, caseins,

whey and mucin proteins (28). Whey and casein are classified according to their solubility, with the

soluble whey proteins present in solution, whilst caseins are present in casein micelles, suspended in

solution (29). Mucins are present in the milk fat globule membrane (27). Proteins present in

significant quantities in the whey fraction are α-lactalbumin, lactoferrin, IgS, serum albumin and

lysozyme (27).

Three types of casein are present in human milk α-, β- and κ-casein. κ-casein stabilises the insoluble

ɑ- and β-caseins forming a colloidal suspension, the casein micelle shown in Figure 3. Caseins do not

form disulfide bonds causing the micelles to form a tangled web structure (30). The total protein

content of human breast milk consists of ~13% casein, the lowest casein concentration of any

studied species, corresponding to the slow growth rate of human infants (31).

sn-3 position

sn-2 position

sn-1 position

Glycerol Fatty acids

R3

R2

R1

Figure 3: Structure of a casein micelle of bovine origin, image from a scanning electron microscope. Reprinted with permission from Elsevier, International Dairy Journal, Volume 14, Issue 12, Dalgleish et al., 2004.

Lactocytes produce approximately 80-90% of breast milk protein. The majority of the breast milk

proteins not synthesised by lactocytes are taken up from the maternal circulation via transcytosis,

passing into the lumen (32).

Non-protein nitrogen

Non-protein nitrogen, consisting of molecules such as urea, creatinine, nucleotides, free amino acids

and peptides, contribute towards ~25% of the total nitrogen present in milk (33). This understudied

fraction of breast milk contains many bioactive molecules. For example, nucleotides are considered

as conditionally essential nutrients during early life, and perform key roles in various cell processes,

such as altering enzymatic activities, and acting as metabolic mediators (34). Furthermore,

nucleotides are known to be beneficial for the development, maturation and repair of the

gastrointestinal tract (34), as well as the development of the microbiota (35), and immune function

(36).

Antibody in breast milk

Immunoglobulins, present in particularly high concentrations early in lactation, are found in breast

milk as secretory IgA (SIgA), the most predominant form, followed by SIgG. These provide

immunological protection to the infant, whilst its own immune system matures (37). The decrease in

antibody reflects the infants’ decreased requirement as their immune system becomes more

functional. Also, this reflects the increasing inability of the infant gut to absorb whole proteins, as

gut permeability to macromolecules decreases over the first few days of life (38).

Protection from invasive pathogens at the mucosal surface relies heavily on breast milk antibodies,

as neonatal secretions only contain trace amounts of SIgA and SIgM (39). In concordance with this,

IgA is found in breast fed infants faeces on the second day of life, compared to 30% of formula-fed

infants (formula does not contain IgA), whose faeces only contains IgA at one month post-partum

(40). The antibodies found in breast milk occur as a result of antigenic stimulation of maternal

mucosa-associated lymphoid tissue (MALT) and bronchial tree (bronchomammary pathway) (41).

Therefore, these antibodies target the infectious agents encountered by the mother during the

perinatal period, meaning they also target the infectious agents most likely to be encountered by the

infant. For example, maternal immunization with a Neisseria meningococcal vaccine demonstrated

elevated N. meningitidis-specific IgA antibodies in breast milk, up to six months post-partum (42).

SIgA is hypothesised to function as the primary protective agent of breast milk (43, 44). In colostrum

SIgA concentrations are around 12 mg/ml whilst mature milk contains only ~1 mg/ml, highlighting

the protective role of colostrum. Breastfed infants ingest approximately 0.5-1.0 g of SIgA per day

(45). SIgA protects against mucosal pathogens via a number of mechanisms, both immobilizing

pathogens, and thereby preventing adherence to epithelial cell surfaces, as well as neutralizing

toxins and virulence factors. SIgA antibodies against bacterial adhesion sites like pili are also found in

breast milk (4, 46). As SIgA is relatively resistant to proteolysis, it is able to provide protection against

pathogens in the gastrointestinal tract (4).

Breast milk contains SIgA antibodies specific for many different enteric and respiratory pathogens.

For example, breast milk contains antibodies protective against Vibrio cholerae, Campylobacter,

Shigella, Giardia lamblia and respiratory tract infections (47-49). SIgA antibodies against bacterial

adhesion sites like pili have been found in breast milk (4, 46). For example, adherence of S.

pneumoniae and Haemophilus influenza to human retropharyngeal cells is blocked by SIgA antibody

in breast milk (46).

Group B Streptococcal antibody in breast milk

Several antibody classes present in breast milk appear to protect against neonatal GBS infection (50).

The administration of GBS specific IgM antibodies via breast milk have been shown to protect

against GBS infection in animal models (51). A similar ability to protect against GBS may be obtained

from breast milk SIgA, however, SIgA does not appear to be taken up into the neonatal circulation,

(52) except in preterm infants (53), suggesting SIgAs effectiveness is limited to the mucosal surfaces

of the gastrointestinal tract in term infants.

However, even if SIgA does not cross into neonatal circulation, these antibodies may still afford

protection to neonates, via other mechanisms. SIgA may interfere with the carbohydrate-mediated

attachment of GBS to nasopharyngeal epithelial cells, reducing the colonizing organism load, and

therefore reducing the morbidity and mortality caused by GBS (54).

IgA antibodies to capsular polysaccharide (CPS) type III GBS have been detected in 63% of a cohort of

70 Swedish mothers (55), whilst IgG antibody concentrations to type Ia, II or III have been found in

concentrations approximately 10% of those found in maternal serum (54). To date, no human

studies have demonstrated a correlation between GBS-antibody levels in breast milk and infant

colonization.

However, using a rodent model, maternal immunization with GBS CPS-II and CPS-III antibody was

shown to increase pup survival when pups were exposed to breast milk containing high titers of

antibody in comparison to low titers (51, 56).

Carbohydrate

A huge variety of different and complex carbohydrates are present in milk with lactose, a

disaccharide consisting of glucose covalently bound to galactose, being the most abundant by far.

Indeed, lactose is present in the highest concentration in humans compared to any other species,

corresponding to the high energy demands of the human brain. Human milk oligosaccharides (HMO)

also make up a significant fraction of breast milk carbohydrate, but are indigestible by the infant,

their function instead is to nourish the gastrointestinal microbiota (57).

Human Milk Oligosaccharides

Human milk oligosaccharides (HMO) are an important component of human milk carbohydrate, and

are the third largest component in breast milk, totalling on average 12.9g/L in mature milk and

20.9g/L at 4 days post-partum (57). HMO contain between 3 to 22 saccharide units per molecule,

and are made up of 5 different sugars, found in varying different sequences and orientations. The

monosaccharides which make up the oligosaccharides are L-fucose, D-glucose, D-galactose, N-

acetylglucosamine and N-acetylneuraminic acid. There are known to be over 200 different types of

oligosaccharide in human milk, all of which feature lactose at the reducing end (58).

HMO function as prebiotics, encouraging the growth of certain strains of beneficial bacteria, such as

bifidobacterium infantis, within the infant gastrointestinal tract, protecting the infant from

colonisation by pathogenic bacteria (59). HMO play an important role in preventing neonatal

diarrhoeal and respiratory tract infections (60, 61).

The production of HMO is genetically determined, different profiles of milk oligosaccharide occur as

a result of specific transferase enzymes expressed in the lactocytes. Two such genes, important for

determining the HMO profile a mother produces, are the Secretor, and Lewis blood group genes.

The Secretor gene encodes for the enzyme α(1,2)-fucosyltransferase (FUT2), responsible for linking

fucose in a α1-2 linkage to elongate the HMO chain. The enzyme FUT3 is encoded for by the Lewis

blood group gene; this enzyme catalyses the reaction between fucose in a α1-3/4 linkage, creating

further fucosylated oligosaccharides, Figure 4. As a result of the different expressions of these

enzymes, there are four main phenotypes in relation to HMO profile; Se +/Le+, Se-/Le+, Se+/Le- and

Se-/Le- (62).

Furthermore, HMO have been observed to modulate intestinal epithelial cell responses, as well as

acting as immune modulators, altering both the environment of the intestine, by reducing cell

growth, and inducing differentiation and apoptosis (63), as well as immune responses, potentially

shifting T-cell responses to a balanced Th1/Th2-cytokine production (64).

One study investigating breast milk HMO profile demonstrated Se+/Le+ mothers produced all types of

fucosylated oligosaccharides, whilst Se-/Le+ mothers did not produce α1,2-fucosylated structures,

such as 2’-fucosyllactose. Se+/Le- mothers secreted α1,2- and α1,3-fucosylated oligosaccharides, but

not HMO containing α1,4-fucose residues (65). However, it was noted that in Se-/Le+ mothers, α1,3-

fucosylated oligosaccharides, such as 3’-fucosyllactose, were between two to fivefold higher than in

Se+/Le+ mother’s breast milk. This suggests there is an increase in FucT3 activity in non-secretor

mothers, meaning that the total oligosaccharide production is relatively equal between the different

groups (65).

One mechanism by which HMO protect infants against gastrointestinal infection is by acting as

receptor decoys. A crucial step in the initiation of infection is the binding of pathogens to

carbohydrates present on intestinal epithelial cells. HMO inhibit this process due to their analogous

shapes to cell surface carbohydrates: pathogens recognise and bind to HMOs anchoring the bacteria

in the mucosal layer and prevent cell adhesion to epithelial cells. Once bound, pathogens pass

harmlessly from the gastrointestinal tract. An observational study found a significant association

between levels of specific 2-linked fucosylated oligosaccharides in human milk and rates of

Campylobacter diarrhoea infection in breast fed infants. Furthermore, infants who received milk

containing a low concentration of lacto-N-difucohexaose had an increased incidence of calicivirus

diarrhoea (66). HMO also prevent the adherence of S. pneumonia (67) and Escherichia coli (68),

suggesting HMO are capable of delivering protection against many bacterial and viral infections. GBS

type Ib and II polysaccharides are virtually identical to certain HMO present in breast milk (56, 69,

70) raising the possibility of cross-reactivity with HMO (71).

Different pathogen receptors have different affinities for specific carbohydrate structures, as the

structures of the HMO produced are genetically determined: mothers possessing different

genotypes, and therefore different HMO profiles, may protect their infants against certain infections

to a greater or lesser extent, depending on the presence of specific HMOs. Likewise, the different

HMO produced alters the types of microbiota colonising infants, as well as the timing of the

establishment of the microbiota (72).

Figure 4: Structure of 2’- and 3’-fucosyllactose. Reproduced from (73).

Influences on breast milk composition

Breast milk composition is extremely complex, varying with the time of day, stage of the nursing

process, and many other factors, with the lipid being most variable in terms of concentration (74).

Time associated changes in breast milk composition

Length of Lactation

Milk is commonly classified into colostrum, transitional milk and mature milk, however, these are

not distinct classes of milk, but refer to the gradual alteration in the content of milk throughout

lactation (33). Colostrum, the first milk produced, is significantly different from mature milk,

containing high concentrations of whey protein, whilst the caseins are almost undetectable (27). The

average content of protein in breast milk gradually decreases from the second month to the seventh

month, after which the speed of reduction of protein content levels off. Colostrum contains low

concentrations of both lactose and fat in comparison to mature milk (33, 75). Lactose production is

highest in the forth to seventh month, after which it decreases, whilst a gradual increase in the

concentration of lipid occurs over lactation (76).

Colostrum is dramatically different to mature breast milk in terms of its bioactive properties,

containing high concentrations of secretory immunoglobulin (77). These qualities suggest that the

primary role of colostrum is not nutritional, but immunologic, protecting the baby as it emerges

from the relatively sterile environment of the womb, to being exposed to many environmental

pathogens. In agreement with this, the concentration of HMO in colostrum is particularly high, being

approximately double that of mature milk, with concentrations reducing from ~21 g/L to ~13 g/L

from day 4 to day 120 post-partum (78).

As well as its immunologic and nutritional roles, colostrum appears to also act as a growth promoter.

Colostrum contains many growth factors, again often in greater concentrations than in mature milk,

for example, epidermal growth factor (79), TGF-β (80) and colony stimulating factor-1 (81) are all

found in higher concentrations in colostrum than mature breast milk.

Time since last feed

One of the most significant predictors of milk fat concentration is the length of time since the last

feed; the longer this interval is, the lower the concentration of fat in the milk. In keeping with this,

fat concentrations at the end of the previous feed, as well as the volume of milk received at the

previous feed, have been found to be particularly important predictors of milk fat concentration

(82).

Stage of the nursing process

The stage of the nursing process results in a large alteration in the composition of breast milk,

responsible for some of the largest variabilities seen in milk composition. There is a gradual increase

in the fat content from the beginning, known as fore milk, to the end of a feed, hind milk, whilst

lactose shows an inverse correlation to the change in fat content (83).

Diurnal variation

A diurnal variation in milk fat concentration occurs, with a peak fat content occurring at midmorning,

and a low overnight, varying from ~5g/100ml to ~3g/100ml (33).

Maternal characteristics altering breast milk composition

Age of Mother

Protein concentration is highest in breast milk of mothers aged 20-30, however, maternal age does

not seem to influence either lipid or lactose concentrations (76), and maternal age does not have a

large impact on breast milk composition.

Diet

The influence of maternal diet on breast milk composition is complex. Depending on the type of

nutrient, maternal diet can have virtually no impact on a nutrients concentration, whilst for other

nutrients, maternal diet can result in large variations (84).

Previous research on the macronutrient content of breast milk from mothers of different ethnicities

found little variation based on diet (85), and the variation in milk lipid concentration appears to be

independent of maternal diet (86). However, the specific fatty acids which form the lipid fraction are

sensitive to maternal diet. These fatty acids are either endogenously synthesised by the mammary

gland, or taken up from the maternal plasma, and both of these fatty acid sources are influenced by

maternal diet (87).

Numerous studies investigating the fatty acid profile of breast milk have noted that it can be altered

by manipulating the maternal diet (87-89), especially the monounsaturated omega-6 and omega–3

fatty acids. Dietary fatty acids are transferred rapidly to breast milk, and within 2 to 3 days breast

milk changes to mimic that of dietary fat (90).

The mammary gland is capable of synthesizing the medium-chain fatty acids (MCFAs) 10:0, 12:0 and

14:0. Women receiving a high carbohydrate, low fat diet have been observed to increase MCFA

synthesis in order to maintain the quantity of triacylglycerides in breast milk (91).

Ethnicity

An analysis summarising research on the composition of milk of mothers from seven countries

suggests breast milk composition is relatively consistent across different ethnicities. Of the variation

which was observed, fat content was seen to vary by the greatest amount. Importantly, the

magnitude of inter-individual variation between mothers of the same ethnicity was as great as that

observed between mothers of different ethnicities (33).

Weight gain during pregnancy

A correlation between maternal weight gain during pregnancy and breast milk fat content has been

reported, however, this was only observed to be significant at four months post-partum. The

authors hypothesise that this phenomenon may be due to the laying down of fat stores during

pregnancy, which are used as an energy reserve during lactation and subsequently more quickly

diminished in the low weight gain group of mothers (92). Despite this finding, two further studies

were unable to identify an association between maternal weight gain during pregnancy and breast

milk fat content (93), (94).

Birth weight

Milk fat concentration increases when a deviation from normal birth weight occurs; i.e. there is a u-

shaped association between fat content and infant birth weight, with a 20-30% increase observed at

the lowest and highest infant birth weights. Protein and carbohydrate concentration do not appear

to change significantly in relation to infant birth weight (2). However, this study did not collect

information on length of gestation; therefore, this influence may simply be a marker of the maturity

of the infant.

Summary

Studying the composition of breast milk can be challenging, in such a dynamic fluid without a

benchmark against which to compare. However, if we are to improve the understanding of the

biology of the lactating mother and her infant, as well as improving the quality of formula milks

produced, investigating this is a necessity. Also, exactly how the composition of breast milk alters,

and the downstream effects this may have on subsequent adult health will be of great interest in

regard to the programming of the human metabolism during this early period.

Many unknowns remain. Although some preliminary data exists, exactly how different profiles of

HMO influence the species and types of bacteria which colonise the infants gastrointestinal tract,

and how these microbiota subsequently influence the biology of the host are all questions of great

interest. Likewise, just how infant genotype influences the environment of the intestine, and how

this influences the species of microbiota present is yet to be delineated. Furthermore, many

components of breast milk alter during digestion, taking on new properties, and the consequences

of this for infant immunity from infection and infant growth have not been sufficiently examined.

Breast milk is vital in protecting infants from neonatal sepsis and for the promotion of infant growth

and development. Its role in the mediation of potentially pathogenic gut organisms is just emerging

and components such as HMO may prove useful adjuncts to antimicrobial therapy.

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