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ABSTRACT
Breast-feeding provides protection against infections and contains numerous
factors that modulate and promote the development of the infant immune
system. These factors include secretory IgA, antimicrobial proteins like
CD14, cytokines, and fatty acids. Studies examining the role of breastfeeding in the development of allergic disease in infants demonstrate
potentially protective as well as neutral or nonprotective effects, likely
due to the heterogeneity in their study design. In this overview, we explore
the potential role of immune factors in the breast milk, as well as selected
probiotics, in the development of allergy.
Key Words: allergy, breast milk, breast-feeding, hypoallergenic formulas,
probiotics
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Secretory IgA
Secretory IgA (sIgA), an important component of breast
milk, is altered in breast-feeding mothers with allergic disease.
sIgA is an immunoglobulin present in both the infant gut and breast
milk that is specifically directed against antigens in the mothers
environment. Infants are unable to produce their own protective
levels until almost 30 days after birth (Fig. 2) (4). Accordingly, sIgA
is at its highest levels in breast milk during the colostral phase, when
the infant needs this immune protein the most. Low levels of sIgA
have been associated with an increased risk of cows-milk allergy in
infants (5). In addition, lower levels of sIgA were found in the
colostrum of allergic mothers compared with nonallergic mothers
(5). However, another study demonstrated that breast milk sIgA
levels did not predict the development of allergic disease in the
children up to 18 months of age (6). These differences demonstrate
the complexity of the relationship between breast milk factors and
the development of allergic disease as well as the heterogeneity
in study design. It is likely that the simultaneous interaction of
multiple breast milk factors is protective.
Soluble CD14
In addition to sIgA, infants in the early postpartum period
also lack CD14, an immunoregulatory protein normally present in
the mature intestine. Increased levels of CD14 are present in
colostrum, but decline in the breast milk with the passage of time.
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12
Human milk
(3 days)
10
8
6
Human milk
(57 days)
% (V/V)
3
Cytokines
Human milk contains an array of cytokines and chemokines,
many of which are closely linked to the development of allergic
disease. Th2 cytokines, like interleukin (IL) 4, IL-5, and IL-13, are
involved in the production of IgE from B cells and are also elevated
in the breast milk of allergic mothers (12). Tolerogenic cytokines,
like transforming growth factor-beta (TGF-b) and IL-10, are
involved in suppressing the inflammatory response and are the
Concentration of sIgA in breastmilk
sIgA total breastmilk protein (mg/gm)
10
A
B
C
D
4
2
10
30
60
Days
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2
0
Food Allergens
Food allergens in cows milk, such as B lactoglobulin,
casein, and whey, can be transferred in the breast milk (19). These
and other food allergens implicated in atopic disease, such as egg
and peanut, can be detected in human breast milk 4 hours after
maternal intake and remain in the milk for several days (20). Breast
milk colitis, also called food proteininduced proctocolitis or
cows-milk protein allergy, is a poorly characterized immune
reaction to a breast milk food protein (mainly milk proteins) and
is the most common food allergy under 2 years of age (21). It causes
blood-streaked stools in otherwise healthy infants and usually
resolves after the mother is placed on a restricted diet. The
pathophysiology of this condition, as well as how other food
antigens found in breast milk lead to infant sensitization and allergic
disease, has not been determined. However, it is possible that these
foreign proteins, in the presence of proinflammatory cytokines
and other immune factors, predispose infants to this condition.
In contrast, it is likely that these same food proteins, in the presence
of other milk factors such as TGF-b and IL-10, lead to mucosal
tolerance. Additional studies are needed to elucidate the role of
these breast milk factors in the development of either infant
sensitization or infant tolerance. Studies investigating these breast
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All
708
Exclusive (10,704,
1211 with atopy)
Exclusive (101)
Subset (1697)
Exclusive (4361)
Subset (746)
Partial BF
Self-reported and/or
medical record at 1 y
Self-reported between
4 and 18 mo
Medical evaluation
at 12 mo
Self-reported at 3 y
Cows-milk
formula
Partial BF
4
Exclusive (2030)
BF frequency
Duration,
mo
Subset (632)
Comparison
group
AD assessment
3903 (nested in
clinical trial)
16,491 (nested
in clinical trial)
15,430
Laubereau
et al (24)
Kramer
et al (25)
Benn et al
(26)
Kerkhof
et al (27)
OR (95% CI)
milk constituents and the infant intestinal response in both outcomes will facilitate a better understanding of the impact of breastfeeding on infant allergic disease.
High risk
for atopy?
Study
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Partial BF
Wetzig (34)
475
All
Exclusive (114)
5
Self-reported at 1 y
Exclusive (179)
All
616 (nested in
clinical trial)
1314
Partial BF
BF frequency
High risk
for atopy?
Entire birth
cohort population
Study
Duration, mo
Subset (1942)
Comparison
group
AD assessment
OR (95% CI)
8346
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Ludvigsson
et al (32)
Mihrshahi
et al (33)
Bergmann
et al (31)
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CONCLUSIONS
Breast milk contains multiple factors that modulate and
promote the development of the infant immune system, including
its potential protective role against allergic disease. These factors
include immunoglobulins such as secretory IgA, antimicrobial
proteins such as CD14, cytokines, and fatty acids. In addition to
providing protection against infections that may promote atopic
disease, breast-feeding also promotes the establishment of an
intestinal microbiota that may protect against atopic disease,
possibly by stimulating tolerogenic cytokines, such as TGF-b,
or stimulating a Th1 response (47). Exclusive breast-feeding, in
addition to having other well-recognized benefits, can protect
against the onset of atopic dermatitis by decreasing exposure to
external allergens, or possibly, presenting them to the infant in a
way that promotes allergen tolerance. This promotion of tolerance
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