The Dynamic Effects of Breastfeeding on Intestinal Development and Host Defense

  • W. Allan Walker
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 554)


In this review, evidence is provided to support the hypothesis that human milk provides a link between the mother and her newborn infant in the extrauterine environment in a manner similar to the placental link between mother and fetus in utero. In addition, breastfeeding helps prevent age-related diseases affecting the gastrointestinal tract during the newborn period. To provide evidence to support this hypothesis, anecdotal clinical studies are sited to suggest that human milk contains factors that may be missing in inherited diseases of inborn errors in metabolism and provide passive protective factors that lessen the expression of neonatal allergic and infectious diseases. In some instances, by providing the missing factor in an inherited disease, the newborn may be protected from serious damage to its developing brain. A second line of evidence to support this hypothesis is the observation that the composition of human milk varies with the infant’s needs. To illustrate this principal, the composition of milk from mothers delivering prematurely and milk of mothers of full-term infants were compared, and the differences in trophic and protective factors in colostrum versus mature milk from mothers delivering full-term are cited. Finally, using observations from, the laboratory that define the immaturities in neonatal and premature human intestinal defenses as the neonate’s host defense deficiency, the specific effect that anti-inflammatory and maturational factors in human milk has on these immaturities is discussed. The active stimulus of maternal milk on the rapid development of host defenses is underscored. These cited examples of human milk effects in the newborn help support the stated hypothesis. Additional studies of human immature gut function along with translational and clinical studies are necessary to provide further objective evidence in support of breastfeeding for all neonates, particularly premature neonates.


Human Milk Newborn Infant Cholera Toxin Congenital Hypothyroidism Mature Milk 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adlerberth I, Hanson LA, Wold AE. The ontogeny of the intestinal flora. In: Sanderson IR, Walker WA, editors. Development of the Gastrointestinal Tract. Hamilton, Ontario: BC Decker, 1999.Google Scholar
  2. Bernt KM, Walker WA. Human milk as a carrier of biochemical messages. Acta Paediatr 1999;430(Suppl):27–41.Google Scholar
  3. Bernt KM, Walker WA. Human milk and the response of intestinal epithelium to infection. In: Newburg DS, editor. Bioactive Components of Human Milk. New York: Kluwer Academic/Plenum Publishers. Adv Exp Med Biol 2001;501:11–30.CrossRefGoogle Scholar
  4. Berseth CL, Michener SR, Nordyke CK, Go VL. Postpartum changes in pattern of gastrointestinal regulatory peptides in human milk. Am J Clin Nutr 1990;51:985–990.PubMedGoogle Scholar
  5. Bode HH, Vanjonack WJ, Crawford JD. Mitigation of cretinism by breast-feeding. Pediatrics 1978;62:13–16.PubMedGoogle Scholar
  6. Caplan MS, Jilling T. New concepts in necrotizing enterocolitis. Curr Opin Pediatr 2001; 13:111–115.PubMedCrossRefGoogle Scholar
  7. Chandra RK. Prospective studies of the effect of breastfeeding on incidence of infection and allergy. Acta Paediatr Scand 1979;68:691–694.PubMedCrossRefGoogle Scholar
  8. Chandra RK. Five year follow-up of high risk infants with family history of allergy who were exclusively breast-fed or fed partial whey hydrolysate, soy, and conventional cow’s milk formulas. J Pediatr Gastroenterol Nutr 1997;24:380–388.PubMedCrossRefGoogle Scholar
  9. Chu SW, Walker WA. Bacterial toxin interaction with the developing intestine. A possible explanation for toxigenic diarrhea of infancy. Gastroenterology 1993;104:916–925.PubMedGoogle Scholar
  10. Chu WS, Ely IG, Walker WA. Age and Cortisol alter host responsiveness to cholera toxin in the developing gut. Am J Physiol 1989;256:G220–G226.PubMedGoogle Scholar
  11. Claud EC, Walker WA. Hypothesis: inappropriate colonization of the premature intestine can cause neonatal necrotizing enterocolitis. FASEB J 2001;15:1398–1403.PubMedCrossRefGoogle Scholar
  12. Claud EC, Savidge T, Walker WA. Modulation of human intestinal epithelial cell interleukin-8 secretion by human milk factors. Pediatr Res 2003;53:419–425.PubMedCrossRefGoogle Scholar
  13. Dai D, Nanthkumar NN, Newburg DS, Walker WA. Role of oligosaccharides and glycoconjugates in intestinal host defense. Proceedings of the Sino-American Symposium, Shanghai. J Pediatr Gastroenterol Nutr 2000;30:S23–33.PubMedGoogle Scholar
  14. Eckhert CD, Sloan MV, Hurley DL. Zinc binding: A difference between human and bovine milk. Science 1997;195:789–790.CrossRefGoogle Scholar
  15. Groer M, Walker WA. What is the role of preterm human milk supplement in the host defenses of the preterm infant? Science vs. Fiction. Adv Pediatr 1996;43:335–358.Google Scholar
  16. Gross SJ, David RJ, Bauman L, Tomarelli RM. Nutritional composition of milk produced by mothers delivering preterm. J Pediatr 1980;96:641–644.PubMedCrossRefGoogle Scholar
  17. Gross SJ, Buckley RH, Wakil SS, McAllister DC, David RJ, Faix RG. Elevated IgA concentration in milk produced by mothers delivered of preterm infants. J Pediatr 1981;99:389–393.CrossRefGoogle Scholar
  18. He Y, Sanderson IR, Walker WA. Uptake, transport and metabolism of exogenous nucleosides in intestinal epithelial cell cultures. J Nutr 1994;124:1942–1949.PubMedGoogle Scholar
  19. Hurley LS, Lonnerdal B, Stanislowski AG. Zinc citrate, human milk and actodermatitis enteropathica. Lancet 1979;1:677–678.PubMedCrossRefGoogle Scholar
  20. Hyslop NE, Kern KC, Walker WA. Lysozyme in human Colostrums and human milk. In: Osserman EF, Canfield RE, Boyshok S, editors. Lysozyme. New York: Academic Press, 1974; pp 449–462.CrossRefGoogle Scholar
  21. Insoft RM, Sanderson IS, Walker WA. The development of immune function within the human intestine and its role in neonatal diseases. Pediatr Clin North Am 1996;43:551–571.PubMedCrossRefGoogle Scholar
  22. Kleinman RE, Walker WA. The enteromammary immune system. Digest Dis Sci 1979;24:876–882.PubMedCrossRefGoogle Scholar
  23. Kliegman RM, Pittard WV, Fanaroff AA. Necrotizing enterocolitis in neonates fed human milk. J Pediatr 1979;95:450–453.PubMedCrossRefGoogle Scholar
  24. Kramer MS. Does breast-feeding help protect against atopic disease? Biology, methodology, and a golden jubilee of controversy. J Pediatr 1988; 112:181–190.PubMedCrossRefGoogle Scholar
  25. Kurscheid T, Holschneider AM. Necrotizing enterocolitis (NEC)—mortality and long-term results. Eur J Pediatr Surg 1993;3:139–143.PubMedCrossRefGoogle Scholar
  26. Lonnerdal B, Stanislowski AF, Hurley LS. Isolation of a low molecular weight zinc binding ligand from human milk. J Inorg Biochem 1980;12:71–78.PubMedCrossRefGoogle Scholar
  27. Lonnerdal B, Hoffman BS, Hurley LS. Zinc and copper binding proteins in human milk. Am J Clin Nutr 1982:36:1170–1176.PubMedGoogle Scholar
  28. Lu L, Baldeon ME, Savidge T, Pothoulakis C, Walker WA. Development of microbial-human enterocyte interaction: Cholera toxin. Pediatr Res 2003;54:212–8.PubMedCrossRefGoogle Scholar
  29. Lucas A, Brooke OG, Morley R, Cole TJ, Bamford MF. Early diet of preterm infants and development of allergic or atopic disease: randomised prospective study. Br Med J 1990a;300:837–840.CrossRefGoogle Scholar
  30. Lucas A, Cole TJ. Human milk and neonatal necrotizing enterocolitis. Lancet 1990b;336:1519.CrossRefGoogle Scholar
  31. Majamaa H, Isolauri E. Probiotics: a novel approach in the management of food allergy. J Allergy Clin Immunol 1997;99:179–185.PubMedCrossRefGoogle Scholar
  32. Mattsby-Baltzer I, Roseanu A, Motas C, Elverfors J, Engberg I, Hanson LA. Lactoferrin or a fragment thereof inhibits the endotoxin-induced interleukin-6 response in human monocytic cells. Pediatr Res 1996;40:257–262.PubMedCrossRefGoogle Scholar
  33. McClelland DBL, McGrath J, Samson RR. Antimicrobial factors in human milk. Studies of concentration and transfer to the infant during the early stages of lactation. Acta Paediatr Scand 1978;271(Suppl):l–20.Google Scholar
  34. Munoz FM, Englund JA, Cheesman CC, Maccato ML, Pinell PM, Nahm MH, Mason EO, Kozinetz CA, Thompson RA, Glezen WP. Maternal immunization with pneumococcal polysaccharide vaccine in the third trimester of gestation. Vaccine 2002:20:826–837.CrossRefGoogle Scholar
  35. Nanthakumar NN, Fusunyan RD, Sanderson I, Walker WA. Inflammation in the developing human intestine: A possible pathophysiologic basis for necrotizing enterocolitis. Proc Natl Acad Sci USA 2000;97:6043–6048.PubMedCrossRefGoogle Scholar
  36. Nanthakumar NN, Dai D, Newburg DS, Walker AW. The role of indigenous microflora in the development of murine intestinal fucosyl- and sialyltransferases. FASEB J Express 10.1096/fj.02–0031fje, November 15, 2002.Google Scholar
  37. Pratha VS, Thompson SM, Hogan DL, Paulus P, Dreilinger AD, Barrett KE, Isenberg JI. Utility of endoscopic biopsy samples to quantitate human duodenal ion transport. J Lab Clin Med 1998;132:512–518.PubMedCrossRefGoogle Scholar
  38. Read LC, Francis GL, Wallace JC, Ballard FJ. Growth factor concentrations and growth-promoting activity in human milk following premature birth. J Dev Physiol 1985;7:135–145.PubMedGoogle Scholar
  39. Rubaltelli FF, Biadaioli R, Pecile P, Nicoletti P. Intestinal flora in breast- and bottle-fed infants. J Perinat Med 1998;26:186–191.PubMedCrossRefGoogle Scholar
  40. Sanderson IR, Ezzell RM, Kedinger M, Erlanger M, Xu ZX, Pringault E, Leon-Robine S, Louvard D, Walker WA. Human fetal enterocytes in vitro: modulation of the phenotype by extracellular matrix. Proc Natl Acad Sci USA 1996;93:7717–7722.PubMedCrossRefGoogle Scholar
  41. Saarinen UM, Kajosaari M. Breastfeeding as prophylaxis against atopic disease: prospective follow-up study until 17 years old. Lancet 1995;346:1065–1069.PubMedCrossRefGoogle Scholar
  42. Savidge TC, Lowe DC, Walker WA. Developmental regulation of intestinal epithelial hydrolyase activity in human jejunal xenografts maintained in severe-combined immunodeficient mice. Pediatr Res 2001;50:196–202.PubMedCrossRefGoogle Scholar
  43. Schanler RJ, Goldblum RM, Garza C, Goldman AS. Enhanced fecal excretion of selected immune factors in very low birth weight infants fed fortified human milk. Pediatr Res 1986;20:711–715.PubMedCrossRefGoogle Scholar
  44. Schiffrin EJ, Carter EA, Walker WA, Frieberg E, Benjamin J, Israel EJ. Influence of prenatal corticosteroids on bacterial colonization in the newborn rat. J Pediatr Gastroenterol Nutr 1993;17:271–275.PubMedCrossRefGoogle Scholar
  45. Seiner JC, Merrill DA, Claman HN. Salivary immuno-globulin and albumin: development during the newborn period. J Pediatr 1968;72:685–689.CrossRefGoogle Scholar
  46. Seo JK, Chu SW, Walker WA. Development of intestinal host defense: An increased sensitivity in the adenylate cyclase response to cholera toxin in suckling rats. Pediatr Res 189;25:225–227.Google Scholar
  47. Shaw JCL. Trace elements in the fetus and young infant. I. Zinc. Am J Dis Child 1979;133:1260–1268.Google Scholar
  48. Tapper D, Klagsburn M, Newman J. Growth factors in early and late lactation. J Pediatr Surg 1979;14:803–807.PubMedCrossRefGoogle Scholar
  49. Wold AE, Adlerberth I. Breast feeding and the intestinal microflora of the infant—implications for protection against infectious diseases. In: Koletzko B, Michaelsen K, Hernell O, editors. Short and Long Term Effects of Breast Feeding on Child Health. New York: Kluwer Academic/Plenum Publishers. Adv Exp Med Biol. 2000;478:77–93.Google Scholar
  50. Xanthou M, Bines J, Walker WA. Human milk and intestinal host defense in newborns. Adv Pediatr 1995;42:171–208.Google Scholar
  51. Zemelman BW, Walker WA, Chu SW. Expression and developmental regulation of Na+, K+ adenosine triphosphatase in the rat small intestine. J Clin Invest 1992; 90:1016–1022.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2004

Authors and Affiliations

  • W. Allan Walker
    • 1
  1. 1.Departments of Nutrition and Pediatrics, Harvard Medical School, and Developmental Gastroenterology LaboratoryMassachusetts General HospitalCharlestownUSA

Personalised recommendations