Effect on oral tolerance development

Through avoidance of too early local immune activation - for instance, limiting the intestinal up-regulation of the co-stimulatory B7 molecules (Brandtzaeg, 1998; Chen et al., 2000), the shielding effect exerted by SIgA from breast milk on the suckling's GALT (see above) may contribute to the establishment of oral tolerance not only against the indigenous microflora, but also against dietary antigens, such as gluten. Antibodies to gluten peptides are present in breast milk (Juto and Holm, 1992) and breast-feeding has in fact been shown to protect significantly against the development of coeliac disease in children, an effect that is unrelated to the time of solid food introduction (Brandtzaeg, 1997a). Early exposure to cow's milk has been suggested to be associated with predisposition to type 1 (insulin-dependent) diabetes, and investigations have particularly focused on immune stimulation by bovine serum albumin (Karjalainen et al., 1992), ß-lactoglobulin (Dahlquist et al., 1992) and insulin (Vaarala et al., 1999). In a recent study, short-term breast-feeding and early introduction of cow's milk were found to be associated with progressive signs of type 1 diabetes-related autoimmunity (Kimpimäki et al., 2001).

On the basis of such observations, it may be tentatively concluded that mixed feeding, rather than abrupt weaning, appears to promote tolerance to food proteins and thereby also avoidance of potentially harmful cross-reactive autoantibodies. This notion is further supported by reports suggesting that cow's milk allergy is more likely to develop in infants whose mothers have relatively low levels of milk IgA antibodies to bovine proteins (Savilahti et al., 1991; Järvinen et al., 2000). It is also noteworthy in this context that allergic mothers appear to have decreased levels of ovalbumin-specific IgA (Casas et al., 2000) and elevated levels of IL-4 (Böttcher et al., 2000) in their breast milk.

The presence of TGF-ß and IL-10 in breast milk might contribute to its tolerogenic properties, because these cytokines exert pronounced immunosup-pressive effects in the gut (Ishizaka et al., 1994; Steidler et al., 2000) and TGF-ß enhances the epithelial barrier function (Planchon et al., 1994). Although still a somewhat controversial issue (Zeiger, 2000), the balance of epidemiological studies supports the view that breast-feeding protects against atopic allergy and asthma (Saarinen and Kajosaari, 1995; Oddy et al., 1999; Kull et al., 2001). Interestingly, TGF-ß has been reported to be present at a higher level in maternal colostrum provided for infants that did not develop atopic eczema during exclusive breast-feeding, compared with those with early-onset symptoms (Kalliomäki et al., 1999). As discussed above, food antigens do appear in breast milk, but dietary restriction during pregnancy and breast-feeding has shown no conclusive effect on the development of atopic diseases in the child (Zeiger, 2000; Hoppu et al., 2001). It remains an open question whether early exposure to small amounts of food antigens may actually have a positive effect on tolerance induction, especially when occurring in its natural context in the gut lumen of a suckling (Johansen et al., 2001).

The Mediterranean Diet Meltdown

The Mediterranean Diet Meltdown

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