Injured animals lick their wounds to clean them and also to hasten their healing. In many ancient cultures, squirting milk in the nose or conjunctiva of sick children and the application of urine or saliva to skin injuries were common medical practices. Lactational products of human and other mammalian species have long been associated with unique healing powers. Human milk, especially mother's own milk, has been considered a complete food for infants of all mammals in many ancient scriptures. More than 2500 years ago, with the evolution of agricultural civilization and domestication of mammals, it was proposed by Charak Sutrasthana that milk obtained from buffalo, cow, sheep, camel, donkey, horse, elephant, and goat, when fed to humans, can improve insomnia, appetite, and sexual drive, help ascites, piles, infestations by worms, skin disorders, muscle weakness, and a variety of other ailments (Athavale, 1977). As investigations by Koch began to establish research methods to study the etiology and pathogenesis of infectious disease in the 1800s, classic observations by Escherich (1888) provided, for the first time, evidence that intestinal flora of the human neonate is exquisitely sensitive to human milk. In studies carried out with col-iform bacteria, he observed that bacteria isolated from the feces of persons on a meat diet possess a very intense ability to solubilize and split complex nitrogen compounds (egg albumin, casein), whereas bacteria from the feces of milk-fed babies utilize only small amounts of such compounds. Escherich stated: "It is noteworthy in connection with this latter property that it must be more than coincidence that if one spreads the feces of milk-fed babies on gelatin plates, not a single colony capable of liquefying the gelatin is found. However, most of the types from the feces of meat-fed persons will liquefy gelatin to a glue-like peptone. Further, both types show a particular effect on different types of sugar that are fermented with the production of acid. They give extensive growth on potato and finally in animal experiments demonstrate pathogenic properties" (Escherich, 1888).
Empirical experience supporting the notion that breast milk may protect against diarrheal diseases of children was reviewed by Hanson et al. (1988): "Analyses of infant mortality in diarrhoea from Sweden and Finland in the early 19 th century showed that there was a peak during the summer. This increased mortality was related to the frequent 'summer diarrhoea' during the warm months of July and August. But this peak of mortality was primarily seen in areas where mothers did not breast-feed. In nearby areas where breast-feeding was the rule, there was no increase, or only a minor increase, in the infant mortality in diarrhoea during the summer. The difference did not relate primarily to socioeconomic factors since breast-feeding could be seen in very poor populations, whereas in the same area the farmers' wives had to leave their babies at home to be fed cow's milk through an unhygienic cow horn while working in the fields during the harvest."
The earliest scientifically documented contribution to our knowledge of milk as an important source of mucosal immunity and its functions in in vivo settings is based on studies by Paul Ehrlich (1854-1915) who, in 1892, demonstrated that maternal immunization and subsequent breastfeeding induced protection against the toxic substances ricin and abrin in suckling mice (Ehrlich, 1892). Based on his studies on transfer of immunity through milk, he clearly emphasized the natural breastfeeding of children and raised his voice against artificial feeding. His studies attempted to document the benefit of breastfeeding in mumps, typhus, and measles. Furthermore, he discussed the possible protective role of breastfeeding on congenital syphilis.
It is now well established that bifidobacteria predominate in the feces of the breast-milk-fed infant. Human, but not cow's, milk contains factors that stimulate colonization with bifidobacteria. This observation was largely possible because of the discovery in 1953 of Bifidobacterium bifidum, a subspecies of bifidobacteria that requires human milk for its growth. Over the years, bifidobacterium has been used anec-dotally and more recently under controlled conditions as a therapeutic modality to prevent and treat diarrheal disease, induce immunomodulation, detoxify the gastrointestinal tract, and restore normal intestinal flora (for review see Bezkorovainy and Miller-Catchpole, 1989). Clinical experience in many countries over the past 2 centuries has suggested a strong link between breastfeeding and protection against diarrheal diseases and against fertility and childbear-ing (Jelliffe and Jelliffe, 1977).
Biologic linkage of the milk and mammary glands to the mucosal immune system was recognized initially by identification of immunoglobulins in milk by Gugler and von Muralt (1959) and Hanson (1961). Subsequent studies led to the identification of secretory IgA (S-IgA) in human milk (Hanson and Johansson, 1961). As these studies were being carried out in Europe, the presence of IgA was demonstrated in other external mucosal secretions by Tomasi and his coworkers (Chodirker and Tomasi, 1963; Tomasi and Zeigelbaum, 1963; Bienenstock and Tomasi, 1968) in the United States. These observations were followed by the definition of antiviral, antibacterial, and antiparasitic activity in S-IgA and other milk immunoglobulins; demonstration of a diverse spectrum of cellular elements and antigen-specific, cell-mediated immune responses; recovery of cytokines; and identification of other nonimmunologic defense factors in mammalian products of lactation.
Finally, several studies have identified intestinal and respiratory tract axes in homing of IgA-committed, antibody- forming cells from the intestinal Peyer's patches and bronchus-associated lymphoid tissues to the mammary glands (Montgomery et al., 1974, 1978; Goldblum et al., 1975; Roux et al., 1977; Fishaut et al., 1981; also see subsequent discussion). During the past 20 years it has become clear that many of the observations made by our ancestors have been proved to be accurate. These include the effects of breastfeeding on mucosal infections, childhood allergy, birth spacing, childhood survival, as well as effects on modulation of immune response and its regulation in autoimmune diseases.
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