Some of the molecules and cells in human milk
actively help infants stave off infection
Doctors have long known that infants who are breast-fed contract
fewer infections than do those who are given formula. Until fairly
recently, most physicians presumed that breast-fed children fared
better simply because milk supplied directly from the breast is
free of bacteria. Formula, which must often be mixed with water
and placed in bottles, can become contaminated easily. Yet even
infants who receive sterilized formula suffer from more meningitis
and infection of the gut, ear, respiratory tract and urinary tract
than do breast-fed youngsters.
The reason, it turns out, is that mother's milk actively helps
newborns avoid disease in a variety of ways. Such assistance is
particularly beneficial during the first few months of life, when
an infant often cannot mount an effective immune response against
foreign organisms. And although it is not the norm in most industrial
cultures, UNICEF and the World Health Organization both advise breast-feeding
to "two years and beyond." Indeed, a child's immune response does
not reach its full strength until age five or so.
All human babies receive some coverage in advance of birth. During
pregnancy, the mother passes antibodies to her fetus through the
placenta. These proteins circulate in the infant's blood for weeks
to months after birth, neutralizing microbes or marking them for
destruction by phagocytes-immune cells that consume and break down
bacteria, viruses and cellular debris. But breast-fed infants gain
extra protection from antibodies, other proteins and immune cells
in human milk.
Once ingested, these molecules and cells help to prevent microorganisms
from penetrating the body's tissues. Some of the molecules bind
to microbes in the hollow space (lumen) of the gastrointestinal
tract. In this way, they block microbes from attaching to and crossing
through the mucosa-the layer of cells, also known as the epithelium,
that lines the digestive tract and other body cavities. Other molecules
lessen the supply of particular minerals and vitamins that harmful
bacteria need to survive in the digestive tract. Certain immune
cells in human milk are phagocytes that attack microbes directly.
Another set produces chemicals that invigorate the infant's own
Breast Milk Antibodies
Antibodies, which are also called immunoglobulins, take five basic
forms, denoted as IgG, IgA, IgM, IgD and IgE. All have been found
in human milk, but by far the most abundant type is IgA, specifically
the form known as secretory IgA, which is found in great amounts
throughout the gut and respiratory system of adults. These antibodies
consist of two joined IgA molecules and a so-called secretory component
that seems to shield the antibody molecules from being degraded
by the gastric acid and digestive enzymes in the stomach and intestines.
Infants who are bottle-fed have few means for battling ingested
pathogens until they begin making secretory IgA on their own, often
several weeks or even months after birth.
The secretory IgA molecules passed to the suckling child are helpful
in ways that go beyond their ability to bind to microorganisms and
keep them away from the body's tissues. First, the collection of
antibodies transmitted to an infant is highly targeted against pathogens
in that child's immediate surroundings. The mother synthesizes antibodies
when she ingests, inhales or otherwise comes in contact with a disease-causing
agent. Each antibody she makes is specific to that agent; that is,
it binds to a single protein, or antigen, on the agent and will
not waste time attacking irrelevant substances. Because the mother
makes antibodies only to pathogens in her environment, the baby
receives the protection it most needs-against the infectious agents
it is most likely to encounter in the first weeks of life.
Second, the antibodies delivered to the infant ignore useful bacteria
normally found in the gut. This flora serves to crowd out the growth
of harmful organisms, thus providing another measure of resistance.
Researchers do not yet know how the mother's immune system knows
to make antibodies against only pathogenic and not normal bacteria,
but whatever the process may be, it favors the establishment of
"good bacteria" in a baby's gut.
Secretory IgA molecules further keep an infant from harm in that,
unlike most other antibodies, they ward off disease without causing
inflammation-a process in which various chemicals destroy microbes
but potentially hurt healthy tissue. In an infant's developing gut,
the mucosal membrane is extremely delicate, and an excess of these
chemicals can do considerable damage. Interestingly, secretory IgA
can probably protect mucosal surfaces other than those in the gut.
In many countries, particularly in the Middle East, western South
America and northern Africa, women put milk in their infants' eyes
to treat infections there. I do not know if this remedy has ever
been tested scientifically, but there are theoretical reasons to
believe it would work. It probably does work at least some of the
time, or the practice would have died out.
An Abundance of Helpful Molecules
Several molecules in human milk besides secretory IgA prevent
microbes from attaching to mucosal surfaces. Oligosaccharides, which
are simple chains of sugars, often contain domains that resemble
the binding sites through which bacteria gain entry into the cells
lining the intestinal tract. Thus, these sugars can intercept bacteria,
forming harmless complexes that the baby excretes. In addition,
human milk contains large molecules called mucins that include a
great deal of protein and carbohydrate. They, too, are capable of
adhering to bacteria and viruses and eliminating them from the body.
The molecules in milk have other valuable functions as well. Each
molecule of a protein called lactoferrin, for example, can bind
to two atoms of iron. Because many pathogenic bacteria thrive on
iron, lactoferrin halts their spread by making iron unavailable.
It is especially effective at stalling the proliferation of organisms
that often cause serious illness in infants, including Staphylococcus
aureus. Lactoferrin also disrupts the process by which bacteria
digest carbohydrates, further limiting their growth. Similarly,
B12 binding protein, as its name suggests, deprives microorganisms
of vitamin B12. Bifidus factor, one of the oldest known disease-resistance
factors in human milk, promotes the growth of a beneficial organism
named Lactobacillus bifidus. Free fatty acids present in milk can
damage the membranes of enveloped viruses, such as the chicken pox
virus, which are packets of genetic material encased in protein
shells. Interferon, found particularly in colostrum-the scant, sometimes
yellowish milk a mother produces during the first few days after
birth-also has strong antiviral activity. And fibronectin, present
in large quantities in colostrum, can make certain phagocytes more
aggressive so that they will ingest microbes even when the microbes
have not been tagged by an antibody. Like secretory IgA, fibronectin
minimizes inflammation; it also seems to aid in repairing tissue
damaged by inflammation.
As is true of defensive molecules, immune cells are abundant in
human milk. They consist of white blood cells, or leukocytes, that
fight infection themselves and activate other defense mechanisms.
The most impressive amount is found in colostrum. Most of the cells
are neutrophils, a type of phagocyte that normally circulates in
the bloodstream. Some evidence suggests that neutrophils continue
to act as phagocytes in the infant's gut. Yet they are less aggressive
than blood neutrophils and virtually disappear from breast milk
six weeks after birth. So perhaps they serve some other function,
such as protecting the breast from infection.
The next most common milk leukocyte is the macrophage, which is
phagocytic like neutrophils and performs a number of other protective
functions. Macrophages make up some 40 percent of all the leukocytes
in colostrum. They are far more active than milk neutrophils, and
recent experiments suggest that they are more motile than are their
counterparts in blood. Aside from being phagocytic, the macrophages
in breast milk manufacture lysozyme, increasing its amount in the
infant's gastrointestinal tract. Lysozyme is an enzyme that destroys
bacteria by disrupting their cell walls.
In addition, macrophages in the digestive tract can rally lymphocytes
into action against invaders. Lymphocytes constitute the remaining
10 percent of white cells in the milk. About 20 percent of these
cells are B lymphocytes, which give rise to antibodies; the rest
are T lymphocytes, which kill infected cells directly or send out
chemical messages that mobilize still other components of the immune
system. Milk lymphocytes seem to behave differently from blood lymphocytes.
Those in milk, for example, proliferate in the presence of Escherichia
coli, a bacterium that can cause life-threatening illness in babies,
but they are far less responsive than blood lymphocytes to agents
posing less threat to infants. Milk lymphocytes also manufacture
several chemicals-including gamma-interferon, migration inhibition
factor and monocyte chemotactic factor-that can strengthen an infant's
own immune response.
Several studies indicate that some factors in human milk may induce
an infant's immune system to mature more quickly than it would were
the child fed artificially. For example, breast-fed babies produce
higher levels of antibodies in response to immunizations. Also,
certain hormones in milk (such as cortisol) and smaller proteins
(including epidermal growth factor, nerve growth factor, insulinlike
growth factor and somatomedin C) act to close up the leaky mucosal
lining of the newborn, making it relatively impermeable to unwanted
pathogens and other potentially harmful agents. Indeed, animal studies
have demonstrated that postnatal development of the intestine occurs
faster in animals fed their mother's milk. And animals that also
receive colostrum, containing the highest concentrations of epidermal
growth factor, mature even more rapidly.
Other unknown compounds in human milk must stimulate a baby's
own production of secretory IgA, lactoferrin and lysozyme. All three
molecules are found in larger amounts in the urine of breast-fed
babies than in that of bottle-fed babies. Yet breast-fed babies
cannot absorb these molecules from human milk into their gut. It
would appear that the molecules must be produced in the mucosa of
the youngsters' urinary tract. In other words, it seems that breast-feeding
induces local immunity in the urinary tract.
In support of this notion, recent clinical studies have demonstrated
that the breast-fed infant has a lower risk of acquiring urinary
tract infections. Finally, some evidence also suggests that an unknown
factor in human milk may cause breast-fed infants to produce more
fibronectin on their own than do bottle-fed babies.
All things considered, breast milk is truly a fascinating fluid
that supplies infants with far more than nutrition. It protects
them against infection until they can protect themselves.
The Author: JACK NEWMAN founded the breast-feeding clinic at the
Hospital for Sick Children in Toronto in 1984 and serves as its
director. He has more recently established similar clinics at Doctors
Hospital and St. Michael's Hospital, both in Toronto. Newman received
his medical degree in 1970 from the University of Toronto, where
he is now an assistant professor. He completed his postgraduate
training in New Zealand and Canada. As a consultant for UNICEF,
he has worked with pediatricians in Africa. He has also practiced
in New Zealand and in Central and South America.
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SCIENTIFIC AMERICAN December 1995 Volume 273 Number 6 Page 76
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How Breast Milk Protects Newborns
By Jack Newman, MD, FRCPC