Harvard Medical School Division of Nutrition

W. Allan Walker, M.D.
Conrad Taff Professor of Nutrition and Pediatrics
Director, Division of Nutrition
Harvard Medical School
Director, Mucosal Immunology Laboratory
Massachusetts General Hospital for Children

Breast Milk as a “Gold Standard” for Protective Nutrients

Breast milk provides a protective link from mother to newborn in the extrauterine environment and helps to prevent clinical disease. As a laboratory, we have investigated the mechanism by which breast milk provides passive and /or active protection for the newborn infant. Most recently, we have used human fetal intestinal models including: 1) fetal small intestinal cell lines; 2) organ culture of fetal vs. older child intestine; and, 3) fetal human xenografts of therapeutically aborted 12 to 16 week fetuses transplanted into the subcutaneous capsule of SCID mice. These techniques are used to determine the specific cellular/molecular mechanism of protection from invasive pathogens and harmful antigens. We know from previous studies that the immature human gut allows for excessive uptake of antigen and increased adherence and translocation of pathologic colonizing bacteria. We also know that the immature human fetal intestine responds excessively to inflammatory stimuli and to intestinal anoxious antigens with a systemic immune response. Using the human model systems, we have shown the components of human milk can reduce excessive inflammation and stimulate the upregulation of innate immune signaling genes to reduce the innate immune inflammatory response. We will also show that oligosaccharides in breast milk, which stimulate the upregulation of bifidobacteria and lactobacillus in the first few weeks of life, can alter enteric innate immune gene regulation. This stimulation by prebiotics in breast milk can downregulate TLRs, their signaling molecules and transcription factors and can upregulate negative regulators of the innate inflammatory response. These observations underscore the protective influence of breast milk by developing adequate active protection in neonates exposed to the extrauterine environment.

Selected references

1. Newburg DS, & Walker WA. Protection of the neonate by the immune system of developing gut and of human milk. Ped. Res. 2007; 61: 3-8.
2. Broekaert I, Nanthakumar NN, & Walker WA. Secreted probiotic factors ameliorate enteropathogenic infection in zinc-deficient human Caco-2 and T84 cell lines. Ped. Res. 2007; 62: 139-144.
3. Claude EC, Savidge T, & Walker WA. Modulation of human intestinal epithelial cell interleukin-8 secretion by human milk factors. Ped. Res. 2003; 53(3): 419-425.