Anti-infective Properties of Human Milk
Introduction
- Human milk is described as a "living fluid" and is "species-specific," containing numerous host defense factors that are absent in animal milk or infant formulas,.
- It provides not only optimum nutrition but also comprehensive protection against infections, significantly reducing morbidity and mortality in infants.
- The anti-infective properties are mediated through a combination of cellular components, immunoglobulins, enzymes, and other bioactive factors,.
Humoral and Soluble Immunological Factors
Secretory Immunoglobulin A (SIgA)
- Breast milk contains immunoglobulins, secretory components, and specifically Secretory IgA (SIgA).
- SIgA consists of an IgA molecule bound to two molecules of the secretory component.
- This structural configuration makes SIgA resistant to proteolytic degradation in the neonatal gut,.
- SIgA offers surface protection to the gastrointestinal (GI) and respiratory tracts, preventing the attachment and invasion of pathogens,.
- While IgG and IgM are present, their levels become undetectable by the second month of lactation, leaving SIgA as the predominant immunoglobulin.
Lactoferrin
- Lactoferrin is a major whey protein, constituting approximately 30% of the whey fraction in human milk.
- It possesses bacteriostatic properties,.
- The primary mechanism of action is binding iron, thereby making it unavailable to iron-dependent bacteria such as E. coli,,.
- Lactoferrin also inhibits E. coli directly.
- In contrast, cow's milk contains only trace amounts of lactoferrin.
Lysozyme
- Lysozyme is an enzyme present in human milk that actively kills bacteria.
- It is found in higher concentrations in colostrum and promotes cell maturation.
- Lysozyme is present in significant amounts in human milk whey proteins but is found only in trace amounts in cow's milk.
The Enteromammary and Bronchomammary Axis
- The specific immunity provided by breast milk is dynamic and targeted.
- Plasma cells that produce SIgA in the mammary gland originate from immunocompetent lymphoid tissue in the mother's gut (Gut-Associated Lymphoid Tissue - GALT) and bronchus (Bronchus-Associated Lymphoid Tissue - BALT).
- This creates an enteromammary and bronchomammary axis, where the mother produces antibodies specific to pathogens she encounters in her environment (which are likely the same pathogens the baby is exposed to) and transfers this specific protection to the infant via milk.
Enzymatic Defense Mechanisms
Bile Salt Stimulated Lipase (BSSL)
- BSSL is a specific enzyme found in human milk that aids in fat digestion.
- Beyond nutrition, BSSL has potent anti-infective properties: it is capable of hydrolyzing bacterial lipids.
- BSSL specifically kills protozoa, including Amoeba and Giardia,.
Peroxidases
- Human milk contains oxidases, lactoperoxidases, and leukocyte myeloperoxidase.
- The peroxidase activity, derived from leukocytes and lactoperoxidase, contributes to the killing of bacteria,.
Other Enzymes
- Xanthine Oxidase: Present in colostrum and breast milk; promotes cell maturation.
- Platelet-Activating Factor (PAF) Acetylhydrolase: Helps block the action of PAF, contributing to the prevention of necrotizing enterocolitis (NEC) (implied context of NEC protection).
Cellular Components
- Macrophages: Breast milk supplies macrophages which offer direct immunity to the baby.
- Lymphocytes: Both T and B lymphocytes are transferred through breast milk.
- T Lymphocytes: Responsible for the transfer of immunological memory to the infant.
- Leukocytes: Contribute myeloperoxidase for bacterial killing.
Bioactive and Prebiotic Factors
Bifidus Factor
- Human milk contains the "bifidus factor," a carbohydrate that promotes the growth of Lactobacillus bifidus,.
- The presence of the bifidus factor, combined with the acidic pH of human milk, leads to the colonization of the infant gut by Lactobacillus bifidus,.
- In breastfed infants, bifidobacteria constitute 60% to 90% of the total fecal microbiota, whereas they comprise less than 1% in formula-fed infants.
- These beneficial bacteria produce lactic acid and acetic acid, creating an acidic environment that inhibits the growth of pathogenic organisms like E. coli and Shigella (competitive inhibition),.
Oligosaccharides and Glycans
- Human milk contains oligosaccharides and mucins.
- Galacto-oligosaccharides (GOS) represent approximately 15% of carbohydrates in breast milk and contribute to the development of healthy microflora.
- These compounds can act as decoy receptors, preventing the attachment of pathogens to the infant's mucosal surfaces.
Other Bioactive Factors
- Nucleotides: Present as non-protein nitrogen, nucleotides enhance the infant's immune response and antibody production,.
- Cytokines and Growth Factors: Milk contains anti-inflammatory cytokines (like IL-10) and growth factors (Epidermal Growth Factor, Nerve Growth Factor) that promote gut maturation and repair, reducing susceptibility to infection,.
- Acute Phase Reactants: Alpha-1 antitrypsin and alpha-1 antichymotrypsin are present in human milk.
Protection Against Specific Pathogens
- Malaria:
- Human milk has a relative deficiency of Para Amino Benzoic Acid (PABA).
- Malaria parasites require PABA for growth; the deficiency in breast milk suppresses the parasite to subclinical levels.
- This suppression allows sufficient antigenic stimulus for the infant to develop an immune response without developing severe disease.
- Transfer of maternal antibodies and T lymphocytes also offers protection against malaria.
- Giardia and Amoeba: Killed specifically by Bile Salt Stimulated Lipase (BSSL).
- E. coli: Inhibited by Lactoferrin (via iron binding) and the acidic gut environment created by Lactobacillus bifidus,.
Epidemiological Evidence of Protection
- Diarrhea: A breastfed baby is 14 times less likely to die from diarrhea compared to a non-breastfed infant.
- Respiratory Infections: Breastfed infants are 4 times less likely to die from respiratory diseases.
- Other Infections: There is a 2.5 times lower mortality risk from other infections in breastfed infants.
- Necrotizing Enterocolitis (NEC): Even small amounts of breast milk (colostrum) given to sick babies on IV fluids can "paint the gut" with immunological factors, promoting gut function and reducing the incidence of NEC.
- Artificial Feeding Risks: Artificial feeding is associated with higher risks of infection due to contamination and the lack of these protective factors, leading to unfavorable gut flora (mainly coliforms) and increased susceptibility to NEC.