
also. They may act by direct inhibition of the growth
of pathogens, inhibition of binding of bacterial
pathogens and toxins to mucosal surfaces, and
promotion of the growth of protective microorgan-
isms. The main antiinfectious agents in human
milk are:
1.
0040 Lactoferrin: most of it (> 90%) is present in milk
in the form of apolactoferrin, which competes
with siderophilic bacteria for ferric iron, thus
impairing the proliferation of pathogenic micro-
organisms. However, lactoferrin may have a more
complex antimicrobial effect since it can sensitize
microorganisms to antibiotics and to the attack of
lysozyme by the release of lipopolysaccharides
from bacterial cell walls.
2.
0041 Digestive products of milk lipids: products of
human milk lipid digestion, especially medium-
chain, mono- and polyunsaturated fatty acids
and monoacylglycerols, exert antiviral, antibacter-
ial, and antifungal activity in vitro. The bile salt-
stimulated lipase of human milk appears to be
important in the production of these antimicrobial
lipids.
3.
0042 Enzymes: peroxidase, which is produced by milk
leukocytes, catalyzes the oxidation of thiocyanate
ions to products with bacteriostactic activity.
Lysozyme cleaves peptidoglycans in the cell wall
of susceptible bacteria, causing their lysis.
4.
0043 Secretory IgA and other immunoglobulins (IgG,
IgM, and IgD): secretory IgA (sIgA) is the principal
immunoglobulin in human milk, secreted as
dimeric IgA bound to a secetory component. Its
concentration is higher in colostrum than in
mature milk. sIgA protects the infant against
mucosal pathogens in the maternal environment,
and its antibody specifity reflects the maternal
immunological experience. It causes agglutination
of bacteria, blocks adhesion of several bacteria,
viruses, and parasites to mucosal surfaces in the
intestinal and respiratory tracts, neutralizes
toxins, and prevents translocation of gut bacteria
through the epithelial barrier.
5.
0044 k-Casein and mucin: like other glycoproteins,
including sIgA, they interact with pathogenic bac-
teria and viruses, possibly through their carbo-
hydrate side chains, inhibiting their adhesion to
epithelial cells, thus preventing microbial colon-
ization and invasion of intestinal tissue.
6.
0045 Oligosaccharides: human milk contains several
complex oligosaccharides, which are monomers
of glucose, galactose, N-acetylglycosamine,
fucose, and neuraminic acid. Almost all carry lac-
tose at the reducing end. Oligosaccharides act as
soluble receptor analogs of epithelial cell surface
carbohydrates and are therefore potent inhibitors
of bacterial adhesion to epithelial surfaces. Their
biological functions are closely related to their
conformation. The nitrogen-containing oligosac-
charides also favor the proliferation of intestinal
bifidobacteria and lactobacilli, resulting in an
acidic intestinal environment, which aids in sup-
pressing the growth of enteric pathogens. Glyco-
proteins, such as lactoferrin and k-casein, exert a
similar effect, ascribed to their oligosaccharide
moiety. Glycoconjugates, such as monosialo-
gangliosides, are receptor analogs for heat-labile
toxins produced by bacteria, thus inhibiting bind-
ing of toxins.
0046Anti-inflammatory factors They protect the infant’s
intestinal tract against inflammatory damage and
modulate inflammatory process. Several antiinfec-
tious agents in human milk also have antiinflamma-
tory activity. For instance, lactoferrin inhibits the
formation of oxygen radicals by scavenging free
iron, inhibits the complement system, and suppresses
cytokine release from macrophages stimulated with
bacterial products. Lysozyme interferes with the pro-
duction of superoxide anion. Enzymes such as cata-
lase and glutathione peroxidase act by degrading and
removing hydrogen peroxide. Somatostatin-like
immunoreactivity has been detected in human milk
and may act as an antiinflammatory factor due to its
immunosuppressive properties. Other antiinflamma-
tory factors present in human milk are cortisol,
epithelial growth factor, polyamines, antioxidants
(ascorbate-like compound, uric acid, b-carotene,
tocopherol), and inhibitors of nonoxidative in-
flammatory systems (prostaglandins and platelet-
activating factor).
0047Immunomodulators Human milk components,
besides providing passive protection for the neonate,
may also directly modulate the immunological devel-
opment of the infant. The immunomodulators in
human milk include bioactive substances which
have other primary biological functions, such as hor-
mones and growth factors, substances that present an
overlapping of their antiinfectious or antiinflamma-
tory properties, and those that are actual immuno-
logical factors, such as cytokines and chemokines.
Some examples of the major immunomodulators in
human milk are prolactin, which may modulate
differentiation and function of gut-associated lymph-
oid tissue (e.g., intraepithelial lymphocytes); antiidio-
typic sIgA, which can provide natural immunization to
the infant by sensitizing it against foreign antigens and
microbial agents; lactoferrin, which suppresses in vitro
antibody production and T-lymphocyte proliferative
3456 LACTATION/Human Milk: Composition and Nutritional Value