Bioactive factors of human milk

Human milk is described as a "living fluid" and is species-specific, containing numerous host defense factors and bioactive components absent in animal milk or infant formulas. These factors go beyond simple nutrition to provide immunological protection, promote gastrointestinal maturation, and stimulate neurodevelopment.

1. Immunological and Anti-Infective Factors

Human milk provides "passive immunity" through a complex array of proteins and cells that protect the naive infant gut and respiratory tract.

Humoral Factors

• Secretory Immunoglobulin A (SIgA):
  • This is the predominant immunoglobulin in breast milk.
  • It consists of an IgA molecule bound to two molecules of the secretory component, which makes it resistant to proteolytic degradation in the acidic environment of the neonatal gut,.
  • SIgA provides surface protection to the gastrointestinal and respiratory tracts, preventing the attachment and invasion of pathogens.
  • It is produced via the Enteromammary and Bronchomammary Axis: Plasma cells producing SIgA in the breast originate from the mother's gut-associated lymphoid tissue (GALT) and bronchus-associated lymphoid tissue (BALT). This ensures the baby receives antibodies specific to the pathogens currently present in the mother's (and baby's) immediate environment.
• Lactoferrin:
  • A major whey protein constituting approximately 30% of the whey fraction (compared to trace amounts in cow's milk),.
  • It is a potent bacteriostatic agent,.
  • Mechanism: It binds iron with high affinity, making it unavailable to iron-dependent bacteria such as E. coli,.
  • It also possesses immunomodulatory properties and direct antimicrobial action.
  • It enhances the absorption of iron and zinc.
• Lysozyme:
  • An enzyme found in higher concentrations in colostrum than in mature milk.
  • It actively kills bacteria by lysing their cell walls.
  • It also promotes cell maturation.
• Mucins and Oligosaccharides:
  • These act as "decoy receptors," preventing the attachment of specific pathogens (bacteria and viruses) to the infant's mucosal surfaces,.
• Fibronectin:
  • Enhances the antimicrobial activity of macrophages.

Cellular Components

• Macrophages: Offer direct immunity by engulfing pathogens.
• Lymphocytes: Both T and B lymphocytes are transferred to the infant. T lymphocytes are responsible for transferring immunological memory.
• Leukocytes: Contribute to the peroxidase activity which aids in bacterial killing.

2. Enzymatic Bioactive Factors

Human milk contains enzymes that not only aid digestion but also serve protective functions.

• Bile Salt Stimulated Lipase (BSSL):
  • This enzyme compensates for the low levels of pancreatic lipase in infants, facilitating fat absorption.
  • Anti-infective role: BSSL is capable of hydrolyzing bacterial lipids and specifically kills protozoa such as Giardia lamblia and Entamoeba histolytica,.
• Platelet-Activating Factor (PAF) Acetylhydrolase:
  • This enzyme blocks the action of PAF, a potent inflammatory mediator.
  • It is believed to protect the infant against Necrotizing Enterocolitis (NEC).
• Peroxidases:
  • Includes lactoperoxidase and leukocyte myeloperoxidase.
  • These enzymes contribute to the oxidative killing of bacteria,.
• Xanthine Oxidase:
  • Promotes cell maturation and is found in significant amounts in colostrum.

3. Growth Factors and Hormones

Breast milk contains a wide range of hormones and growth factors that regulate metabolism and tissue development.

• Epidermal Growth Factor (EGF):
  • Promotes the growth and repair of the intestinal epithelium.
  • Essential for luminal surveillance and gut maturation.
• Nerve Growth Factor (NGF):
  • Promotes neural growth and dendritic arborization, contributing to CNS development,.
• Insulin-like Growth Factors (IGF):
  • Includes IGF-1 (Somatomedin C) and IGF-11.
  • These act as growth mediators.
• Hormones:
  • Thyroid Hormones (TSH, Thyroxine): Present in milk; thyroxine binding proteins are also high,.
  • Insulin and Somatostatin: Regulate glucose metabolism and growth.
  • Prolactin and Neurotensin: Present in breast milk.
  • Beta-Casomorphin: A specific CNS growth factor found in human milk.
  • Erythropoietin: Also present.

4. Bifidus Factor and Prebiotics

• Bifidus Factor:
  • A specific carbohydrate (nitrogen-containing polysaccharide) that promotes the growth of Lactobacillus bifidus,.
  • In breastfed infants, bifidobacteria constitute 60–90% of fecal flora, compared to <1% in formula-fed infants.
  • Mechanism: The proliferation of lactobacilli, combined with the low buffering capacity of breast milk, creates an acidic environment (high lactic and acetic acid). This acidity inhibits the growth of pathogenic organisms like E. coli, Shigella, and yeast (competitive inhibition).
• Galacto-oligosaccharides (GOS):
  • Represent approximately 15% of carbohydrates in breast milk.
  • They act as prebiotics, contributing to the development of a healthy gut microflora.

5. Bioactive Nutrients with Specific Roles

• Nucleotides:
  • Present as non-protein nitrogen.
  • They enhance the infant's antibody response and improve the intestinal flora,.
• Long Chain Polyunsaturated Fatty Acids (LCPs):
  • Specifically Docosahexaenoic acid (DHA) and Arachidonic acid (ARA).
  • Essential for brain growth, myelination, and retinal development,.
  • LCPs in breast milk reduce the risk of dyslexia and hyperactivity.
  • They are present in breast milk in the 'trans' form, whereas microwaving formula can convert amino acids to the neurotoxic 'cis' form (though the source context here refers to amino acids, LCPs are lipid components critical for structure).
• Para Amino Benzoic Acid (PABA):
  • Human milk has a relative deficiency of PABA.
  • Since the malaria parasite requires PABA for growth, this deficiency suppresses the parasite to subclinical levels, allowing the infant to develop immunity without severe disease.
• Taurine:
  • An amino acid found in high concentrations in human milk (whey fraction).
  • It functions as a neurotransmitter and neuromodulator, essential for brain and retinal development.
• Carnitine:
  • High levels in breast milk facilitate the transport of long-chain fatty acids across mitochondrial membranes for oxidation, essential for energy production in the newborn,.

6. Summary of Bioactive Components vs. Cow's Milk