Human Breast Milk: Bioactive Components, from Stem Cells to Health Outcomes


Purpose of Review

Breast milk (BM) is a peculiar fluid owing unique properties and resulting the ideal food during early neonatal period. As widely known, it can improve the outcome of both neonate and lactating mother, influencing their whole life. BM is characterized by several beneficial components; among these, a great role is played by BM own and specific microbiome, deeply investigated in many studies. Moreover, the use of metabolomics in BM analysis allowed a better characterization of its metabolic pathways that vary according to lactation stage and neonatal gestational age. The aim of this review is to describe growth factors, cytokines, immunity mediators, and stem cells (SCs) contained in BM and investigate their functions and effects on neonatal outcome, especially focusing on immuno- and neurodevelopment.

Recent Findings

We evaluated recent and updated literature on this field. The article that we analyzed to write this review have been found in MEDLINE using breast milk-derived stem cells, biofactors, growth factors, breastfeeding-related outcomes, neurodevelopment, and neonatal immunological system as keywords. Discovering and characterizing BM components could result very useful to clarify the pathophysiology of their influence on neonatal growth and even to improve artificial formulations’ composition. Moreover, since SCs abilities and their involvement in the development of several diseases, they could help to discover specific targets for new therapies.


It could be useful to characterize BM-derived SC markers, properties, and variations during lactation stages, to understand their potential role in therapeutic applications, since they could be noninvasively isolated from BM. More studies will help to describe more in detail the characteristics of mother-to-child communication through breastfeeding and its potential role in the next future.

This is a preview of subscription content, log in to check access.

Access options

Buy single article

Instant unlimited access to the full article PDF.

US$ 39.95

Price includes VAT for USA

Subscribe to journal

Immediate online access to all issues from 2019. Subscription will auto renew annually.

US$ 99

This is the net price. Taxes to be calculated in checkout.



α-linolenic acid


Arachidonic acid


Antibacterial peptides


Brain-derived neurotrophic factor


Breast milk


Breast milk-derived stem cells


Body mass index




Birth weight


Chronic lung disease


Cluster of differentiation




Central nervous system


C-reactive protein




Docosahexaenoic acid


Epidermal growth factor


Epidermal growth factor


Extremely low birth weight


Epithelial-mesenchymal transition


Fatty acids


Fibroblast growth factors


Gestational age


Granulocyte-colony stimulating factor


Glial cell line-derived neurotrophic factor


Growth factors


Glucagon-like peptide-1


Heparin-binding epidermal growth factor


Embryonic SCs


Hepatocyte growth factor


Human milk oligosaccharides








Insulin growth factors




Linoleic acid




Milk fat globule membrane




Mesenteric lymph nodes


Mesenchymal stem cells


Mucin 1


Homeobox protein


Necrotizing enterocolitis


Neonatal intensive care unit


Natural killers




Octamer-binding transcription factor 4


Retinopathy of prematurity


Stem cells


Small for GA




Sex determining region Y-box


Side population


tdTomato + cells


Transforming growth factor


Tumor necrosis factors


Vascular endothelial growth factor


Very low birth weight


Xanthine oxidoreductase




Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.

    Reali A, Puddu M, Pintus MC, Marcialis MA, Pichiri G, Coni P, et al. Multipotent stem cells of mother’s milk. JPNIM. 2016;5:e50103.

  2. 2.

    Hassiotou F, Heath B, Ocal O, Filgueira L, Geddes D, Hartmann P, et al. Breastmilk stem cell transfer from mother to neonatal organs. FASEB J. 2014;28:216.4.

  3. 3.

    Sakaguchi K, Koyanagi A, Kamachi F, Harauma A, Chiba A, Hisata K, et al. Breast-feeding regulates immune system development via transforming growth factor- beta in mice pups. Pediatr Int. 2018;60:224–31.

  4. 4.

    Brenmoehl J, Ohde D, Wirthgen E, Hoeflic A. Cytokines in milk and the role of TGF-beta. Best Pract Res Clin Endocrinol Metab. 2018;32:47–56.

  5. 5.

    Garofalo R. Cytokines in human milk. J Pediatr. 2010;156:S36e40.

  6. 6.

    Fanos V, Pintus R, Reali A, Dessì A. Miracles and mysteries of breast milk: from Egyptians to the 3 M’s (metabolomics, microbiomics, multipotent stem cells). JPNIM. 2017;6:e060204.

  7. 7.

    Demmelmair H, Prell C, Timby N, Lonnerdal B. Benefits of lactoferrin, osteopontin and milk fat globule membranes for infants. Nutrients. 2017;9:E817.

  8. 8.

    AAP. Breastfeeding and maternal and infant health outcomes in developed countries. AAP Grand Rounds. 2007;18:15–6.

  9. 9.

    Fanos V. Metabolomics, milk-oriented microbiota (MOM) and multipotent stem cells: the future of research on breast milk. JPNIM. 2015;4:e040115.

  10. 10.

    German BJ, Smilowitz JT, Lebrilla CB. Metabolomics and milk: the development of the microbiota in breastfed infants. In: Kochhar S, Martin F-P, editors. Metabonomics and gut microbiota in nutrition and disease (Molecular and integrative toxicology). London: Humana press (Springer); 2015. p. 147–67.

  11. 11.

    Anatolitou F. Human milk benefits and breastfeeding. JPNIM. 2012;1:11–8.

  12. 12.

    Yang T, Zhang L, Bao W, Rong S. Nutritional composition of breast milk in Chinese women: a systematic review. Asia Pac J Clin Nutr. 2018;27:491–502.

  13. 13

    •• Bardanzellu F, Fanos V, Strigini FAL, Artini PG, Peroni DG. Human breast milk: exploring the linking ring among emerging components. Front Pediatr. 2018;6:215. summarizing the last evidence regarding metabolomics and microbiomics in human breast milk.

  14. 14.

    Pecoraro L, Agostoni C, Pepaj O, Pietrobelli A. Behind human milk and breastfeeding: not only food. Int J Food Sci Nutr. 2018;69:641–6.

  15. 15.

    Cesare Marincola F, Dessì A, Corbu S, Reali A, Fanos V. Clinical impact of human breast milk metabolomics. Clin Chim Acta. 2015;451:103–6.

  16. 16.

    Kaingade P, Somasundaram I, Nikam A, Behera P, Kulkarni S, Patel J. Breast milk cell components and its beneficial effects on neonates: need for breast milk cell banking. JPNIM. 2017;6:060115.

  17. 17.

    Garwolińska D, Namieśnik J, Kot-Wasik A, Hewelt-Belka W. Chemistry of human breast milk. A comprehensive review of the composition and role of milk metabolites in child development. J Agric Food Chem. 2018;66:11881–96.

  18. 18.

    Bardanzellu F, Faa G, Fanni D, Fanos V, Marcialis MA. Regenerating the womb: the good, bad and ugly potential of the endometrial stem cells. Curr Reg Med. 2017;7:33–45.

  19. 19.

    Witkowska-Zimny M, Kaminska-El-Hassan E. Cells of human breast milk. Cell Mol Biol Lett. 2017;22:11.

  20. 20.

    Baudesson de Chanville A, Brevaut-Malaty V, Garbi A, Tosello B, Baumstarck K, Gire C. Analgesic effect of maternal human milk odor on premature neonates: a randomized controlled trial. J Hum Lact. 2017;33:300–8.

  21. 21.

    Badiee Z, Asghari M, Mohammadizadeh M. The calming effect of maternal breast milk odor on premature infants. Pediatr Neonatol. 2013;54:322–5.

  22. 22.

    Rioualen S, Durier V, Hervé D, Misery L. Cortical pain response of newborn infants to venepuncture: a randomised controlled trial comparing analgesic effects of sucrose versus breastfeeding. Clin J Pain. 2018;34:1.

  23. 23.

    Sundekilde UK, Downey E, O’Mahony JA, O’Shea CA, Ryan CA, Kelly AL, et al. The effect of gestational and lactational age on the human milk metabolome. Nutrients. 2016;8:304.

  24. 24.

    Hurst NM. The 3 M’s of breast-feeding the preterm infant. J Perinat Neonatal Nurs. 2007;21:234–9.

  25. 25.

    Kobata R, Tsukahara H, Ohshima Y, Ohta N, Yokuriki S, Mayumi M. High levels of growth factors in human breast milk. Early Hum Dev. 2008;84:67–9.

  26. 26.

    Underwood MA. Human milk for the premature infant. Pediatr Clin N Am. 2013;60:189–207.

  27. 27.

    Bhatia J. Human milk and the premature infant. Ann Nutr Metab. 2013;62:8–14.

  28. 28.

    Paul VK, Singh M, Srivastava LM, Arora NK, Deorari AK. Macronutrient and energy content of breast milk of mothers delivering prematurely. Indian J Pediatr. 1997;64:379–82.

  29. 29.

    Bauer J, Gerss J. Longitudinal analysis of macronutrients and minerals in human milk produced by mothers of preterm infants. Clin Nutr. 2011;30:215–20.

  30. 30.

    Bardanzellu F, Fanos V, Reali A. “Omics” in human colostrum and mature milk: looking to old data with new eyes. Nutrients. 2017;9:843.

  31. 31.

    Yang M, Cao X, Wu R, Liu B, Ye W, Yue X, et al. Comparative proteomic exploration of whey proteins in human and bovine colostrum and mature milk using iTRAQ-coupled LC-MS/MS. Int J Food Sci Nutr. 2017;68:671–81.

  32. 32.

    LeBouder E, Rey-Nores JE, Raby AC, Affoltern M, Vidal K, Thornton CA, et al. Modulation of neonatal microbial recognition: TLR-mediated innate immune responses are specifically and differentially modulated by human milk. J Immunol. 2006;176:3742–52.

  33. 33.

    Levy O. Innate immunity of the newborn: basic mechanism and clinical correlates. Nat Rev Immunol. 2007;7:379–90.

  34. 34.

    Cacho NT, Lawrence RM. Innate immunity and breast milk. Front Immunol. 2017;8:584.

  35. 35.

    Kaingade PM, Somasundaram I, Nikam AB, Sarang SA, Patel JS. Assessment of growth factors secreted by human breastmilk mesenchymal stem cells. Breastfeed Med. 2016;11:26–31.

  36. 36.

    Castellote C, Casillas R, Ramirez-Santana C, Perez-Cano FJ, Castell M, Moretones MG, et al. Premature delivery influences the immunological composition of colostrum and transitional and mature human milk. J Nutr. 2011;141:1181–7.

  37. 37.

    Hamosh M. Bioactive factors in human milk. Pediatr Clin N Am. 2001;48:69–86.

  38. 38.

    Jones C, Mackay A, Grigoriadis A, Cossu A, Reis-Filho JS, Fulford L, et al. Expression profiling of purified normal human luminal and myoepithelial breast cells: identification of novel prognostic markers for breast cancer. Cancer Res. 2004;64:3037–45.

  39. 39.

    Nikadi PO, Merrit TA, Pillers DA. An overview of pulmonary surfactant in the neonate: genetics, metabolism, and the role of surfactant in health and disease. Mol Genet Metab. 2009;97:95–101.

  40. 40.

    Jimenez-Gomez G, Benavente-Fernandez I, Matias-Vega M, Lechuga-Campoy JL, Saez-Benito A, Lechuga-Sancho AM, et al. Hepatocyte growth-factor as an indicator of neonatal maturity. J Pediatr Endocrinol Metab. 2013;26:709–14.

  41. 41.

    Ruiz L, Espinosa-Martos I, García-Carral C, Manzano S, McGuire MK, Meehan CL, et al. What’s normal? Immune profiling of human milk from healthy women living in different geographical and socioeconomic settings. Front Immunol. 2017;8:696.

  42. 42.

    Moles L, Manzano S, Fernández L, Montilla A, Corzo N, Ares S, et al. Bacteriological, biochemical and immunological properties of colostrum and mature milk from mothers extremely preterm infants. J Pediatr Gastroenterol Nutr. 2015;60:120–6.

  43. 43.

    Schack-Nielsen L, Michaelsen KF. Breastfeeding and future health. Curr Opin Clin Nutr Metab Care. 2006;9:289–96.

  44. 44.

    Patki S, Patki U, Patil R, Indumathi S, Kaingade P, Bulbule A, et al. Comparison of the levels of the growth factors in umbilical cord serum and human milk and its clinical significance. Cytokine. 2012;59:305–8.

  45. 45.

    Zachary I. VEGF signaling: integration and multi-tasking in endothelial cell biology. Biochem Soc Trans. 2003;31:1171–7.

  46. 46.

    Siafakas C, Anatolitou F, Fusunyan RD, Walker WA, Sanderson IR. Vascular endothelial growth factor (VEGF) is present in human breast milk and its receptor is present on intestinal epithelial cells. Pediatr Res. 1999;45:652–7.

  47. 47.

    Funakoshi H, Nakamura T. Hepatocyte growth factor: from diagnosis to clinical application. Clin Chim Acta. 2003;327:1–23.

  48. 48.

    Collado MC, Santaella M, Mira-Pascual L, Martinez-Arias E, Khodayar-Pardo P, Ros G, et al. Longitudinal study of cytokine expression, lipid profile and neuronal growth factors in human breast milk from term and preterm. Nutrients. 2015;19:8577–91.

  49. 49.

    Peila C, Coscia A, Bertino E. Holder pasteurization affects S100B concentrations in human milk. J Matern Fetal Neonatal Med. 2017;28:1–5.

  50. 50.

    Torres-Castro P, Abril-Gil M, Rodríguez-Lagunas MJ, Castell M, Perez-Cano FJ, Franch A. TGF-Beta 2, EGF, and FGF21 growth factors present in breast milk promote mesenteric lymph node lymphocytes maturation in suckling rats. Nutrients. 2018;10:E1171.

  51. 51.

    Young BE, Levek C, Reynolds RM, Rudolph MC, MacLean P, Hernandez PL, et al. Bioactive components in human milk are differentially associated with rates of lean and fat mass deposition in infants of mothers with normal vs. elevated BMI. Pediatr Obes. 2018;13:598–606.

  52. 52.

    Murphy J, Pfeiffer RM, Lynn BCD, Caballero AI, Browne EP, Punska EC, et al. Pro-inflammatory cytokines and growth factors in human milk: an exploratory analysis of racial differences to inform breast cancer etiology. Breast Cancer Res Treat. 2018;172:209–19.

  53. 53.

    • Sitarik AR, Bobbitt KR, Havstad SL, Fujimura KE, Levin AM, Zoratti EM, et al. Breast milk TGF beta is associated with neonatal gut microbial composition. J Pediatr Gastroenterol Nutr. 2018;65:e60–7. study investigating the role of BM TGFβ1, TGFβ2, and IL-10 in shaping the neonatal gut microbiome in 52 mother-child couples, modulating neonatal outcome and including neonatal immune system development.

  54. 54.

    Abstract from the Academy of breastfeeding medicine 20th Annual international meeting Los Angeles California. Breastfeed Med. 2015;10:1–20.

  55. 55.

    MohanKumar K, Namachivayam K, Ho TT, Torres BA, Ohls RK. Cytokines and growth factors in the developing intestine and during necrotizing enterocolitis. Semin Perinatol. 2017;41:52–60.

  56. 56.

    Munblit D, Abrol P, Sheth S, Chow LY, Khaleva E, Asmanov A, et al. Levels of growth factors and IgA in the colostrums of women from Burundi and Italy. Nutrients. 2018;10:E1216.

  57. 57.

    Kaingade P, Somasundaram I, Sharma A, Patel D, Marappagounder D. Cellular components, including stem-like cells, of preterm mother’s mature milk as compared with those in her colostrum: a pilot study. Breastfeed Med. 2017;12:446–9.

  58. 58.

    Lee H, Padhi E, Hasegawa Y, Larke J, Parenti M, Wang A, et al. Compositional dynamics of the milk fat globule and its role in infant development. Front Pediatr. 2018;6:313.

  59. 59.

    Khan MU, Pirzadeh M, Förster CY, Shityakov S, Shariati MA. Role of milk-derived antibacterial peptides in modern food biotechnology: their synthesis, applications and future perspectives. Biomolecules. 2018;8:E110.

  60. 60.

    Nunes M, da Silva CH, Bosa VL, Rombaldi Bernardi J, Ribas Werlang IC, Zubaran GM, et al. Could a remarkable decrease in leptin and insulin levels from colostrums to mature milk contribute to early growth catch-up of SGA infants? BMC Pregnancy Childbirth. 2017;17:410.

  61. 61.

    Whitaker KM, Marino RC, Haapala JL, Foster L, Smith KD, Teague AM, et al. Associations of maternal weight status before, during and after pregnancy with inflammatory markers in breast milk. Obesity. 2018;26:1659–60.

  62. 62.

    Twigger AJ, Küffer GK, Geddes DT, Filgueria L. Expression of granulisyn, perforin and granzymes in hum and milk over lactation and in the case of maternal infection. Nutrients. 2018;10:E1230.

  63. 63.

    Pichiri G, Lanzano D, Piras M, Dessì A, Reali A, Puddu M, et al. Human breast milk stem cells: a new challenge for perinatologists. JPNIM. 2016;5:050120.

  64. 64.

    Hassiotou F, Geddes DT, Hartmann PE. Cells in human milk: state of the science. J Hum Lact. 2013;29:171–82.

  65. 65.

    Ballard O, Morrow AL. Human milk composition: nutrients and bioactive factors. Pediatr Clin N Am. 2013;60:49–74.

  66. 66.

    Cregan MD, Fan Y, Appelbee A, Brown ML, Klopcic B, Koppen J, et al. Identification of nestin-positive putative mammary stem cells in human breastmilk. Cell Tissue Res. 2007;329:129–36.

  67. 67.

    Hosseini SM, Talaei-Khozani T, Sani M, Owrangi B. Differentiation of human breast-milk stem cells to neural stem cells and neurons. Neurol Res Int. 2014;807896.

  68. 68.

    Patki S, Kadam S, Chandra V, Bhonde R. Human breast milk is a rich source of multipotent mesenchymal stem cells. Hum Cell. 2010;23:35–40.

  69. 69.

    Hassiotou F, Beltran A, Chetwynd E, Stuebe AM, Twigger AJ, Metzger P, et al. Breastmilk is a novel source of stem cells with multilineage differentiation potential. Stem Cells. 2012;30:2164–74.

  70. 70.

    Kakulas F, Jeddes DT, Hartmann PE. Breastmilk is unlikely to be a source of mesenchymal stem cells. Breastfed Med. 2016;11:150–1.

  71. 71.

    Twigger A, Hepworth AR, Lai CT, Chetwynd E, Stuebe AM, Blancafort P, et al. Gene expression in breastmilk cells is associated with maternal and infant characteristics. Sci Rep. 2015;5:12933.

  72. 72.

    Hennighausen L, Robinson GW. Signaling pathways in mammary gland development. Dev Cell. 2001;1:467–75.

  73. 73.

    Wiseman BS, Werb Z. Stromal effects on mammary gland development and breast cancer. Science. 2002;296:1046–9.

  74. 74.

    Russo J, Russo IH. Development of the human breast. Maturitas. 2004;49:2–15.

  75. 75.

    Dontu G, Abdallah WM, Foley JM, Jackson KW, Clarke MF, Kawamura MJ, et al. In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells. Genes Dev. 2003;17:1253–70.

  76. 76.

    Fan Y, Chong YS, Choolani MA, Cregan MD, Chan JK. Unravelling the mystery of stem/progenitor cells in human breastmilk. PLoS One. 2010;5:14421.

  77. 77.

    Twigger AJ, Hodgetts S, Filgueira L, Hartmann PE, Hassiotou F. From breast milk to brains: the potential of stem cells in human milk. J Hum Lact. 2013;29:136–9.

  78. 78.

    Esmailpour T, Huang T. TBX3 promotes embryonic stem cell proliferation and neuroepithelial differentiation in a differentiation stage-dependent manner. Stem Cells. 2012;30:2152–63.

  79. 79.

    Faa G, Fanos V, Puddu M, Reali A, Dessì A, Pichiri G, et al. Breast milk stem cells: four questions looking for an answer. JPNIM. 2016;5:050203.

  80. 80.

    Sani M, Hosseini SM, Salmannejad M, Aleahmad F, Ebrahimi S, Jahanshahi S, et al. Origins of the breast milk-derived cells; an endeavor to find the cell sources. Cell Biol Int. 2015;39:611–8.

  81. 81.

    Indumathi S, Dhanasekaran M, Rajkumar JS, Sudarsanam D. Exploring the stem cell and non-stem cell constituents of human breast milk. Cytotechonology. 2013;65:385–93.

  82. 82.

    Field CJ. The immunological components of human milk and their effect on immune development in infants. J Nutr. 2005;135:1–4.

  83. 83.

    • Briere CE, McGrath JM, Jensen T. Breast milk stem cells. Paper presented at Pediatric Academic Society Baltimora. 2016. This article summarizes the current evidence regarding breast milk derived stem cells (BMDSCs), especially in relation to different stage of lactation, expressed markers and lineages.

  84. 84.

    Cairns J. Somatic stem cells and the kinetics of mutagenesis and carcinogenesis. Proc Natl Acad Sci U S A. 2002;99:10567–70.

  85. 85.

    Hong Y, Stambrook PJ. Restoration of an absent G1 arrest and protection from apoptosis in embryonic stem cells after ionizing radiation. Proc Natl Acad Sci U S A. 2004;101:14443–8.

  86. 86.

    •• Briere CE, Jensen T, Young EE MGJM, Finck C. Stem-like cell characteristics from breast milk of mothers with preterm infants as compared to mothers with term infants. Breast Feed Med. 2017;12:174–9. demonstrating that SCs content differs in BM from mothers delivering term and preterm neonates. Comparing samples from preterm neonates (born before than 37 weeks of GA) with full term samples, a different percentage and a variable expression of SCs ‘markers was highlighted.

  87. 87.

    Walker TL, Kempermann G. One mouse, two cultures: isolation and culture of adult neural stem cells from the two neurogenic zones of individual mice. J Vis Exp. 2014;84:51225.

  88. 88.

    McGregor JA, Rogo LJ. Breast milk: an unappreciated source of steam cells. J Hum Lact. 2006;22:270–1.

  89. 89.

    Hassiotou F, Hartmann PE. At the dawn of a new discovery: the potential of breast milk stem cells. Adv Nutr. 2014;5:770–8.

  90. 90.

    Li CY, Wu XY, Tong JB, Yang XX, Zhao JL, Zheng QF, et al. Comparative analysis of human mesenchymal stem cells from bone marrow and adipose tissue under xeno-free conditions for cell therapy. Stem Cell Res Ther. 2015;6:55.

  91. 91.

    Burlacu A, Grigorescu G, Rosca A, Preda MB, Simionescu M. Factors secreted by mesenchymal stem cells and endothelial progenitor cells have complementary effects on angiogenesis in vitro. Stem Cells Dev. 2013;22:643–53.

  92. 92.

    Schneider N, Garcia-Rodenas CL. Early nutritional interventions for brain and cognitive development in preterm infants: a review of the literature. Nutrients. 2017;9:E187.

  93. 93.

    González HF, Visentin S. Micronutrients and neurodevelopment: an update. Arch Argent Pediatr. 2016;114:570–5.

  94. 94.

    Hernell O, Timby N, Domellöf M. Clinical benefits of milk fat globule membranes for infants and children. J Pediatr. 2016;173:60–5.

  95. 95.

    González HF, Visentin S. Nutrients and neurodevelopment: lipids. Arch Argent Pediatr. 2016;114:472–6.

  96. 96.

    Bertino E, Di Nicola P, Giuliani F, Peila C, Cester E, Vassia C, et al. Benefits of human milk in preterm infant feeding. J Pediatr Neonatal Individ Med. 2012;1:19–24.

  97. 97.

    Furman L, Taylor G, Minich N, Hack M. The effect of maternal milk on neonatal morbidity of very low-birth-weight infants. Arch Pediatr Adolesc Med. 2003;157:66–71.

  98. 98.

    Meinzen-Deer J, Poindexter B, Wrage L, Morrow AL, Stoll B, Donovan EF. Role of human milk in extremely low birth weight infants risk of necrotizing enterocolitis or death. J Perinatol. 2009;29:57–62.

  99. 99.

    American Academy of Pediatrics. Section on breastfeeding. Breastfeeding and the use of human milk. 2012;129:827–41.

  100. 100

    •• Jimènez BC, Parada YA, Marin AV, de Pipaon Marcos MS. Beneficios a corto, medio y largo plazo de la ingesta de leche humana en recien nacidos de muy bajo peso. Short, medium and long term benefits of human milk intake in very low birth weight infants. Nutr Hosp. 2017;34:5. demonstrating a better neurodevelopmental outcome at two years and a better score in the global and verbal cognitive area at five years of age in a population of 152 very low birth weight (VLBW) neonates assuming BM since the first weeks of life.

  101. 101.

    Belfort MB, Ehrenkranz RA. Neurodevelopmental outcomes and nutritional strategies in very low birth weight infants. Semin Fetal Neonatal Med. 2017;22:42–8.

  102. 102.

    Colaizy TT, Carlson S, Saftlas AF, Morriss FH Jr. Growth in VLBW infants fed predominantly fortified maternal and donor human milk diets: a retrospective cohort study. BMC Pediatr. 2012;12:124.

  103. 103.

    Roze JC, Darmaun D, Boquien CY, Flamant C, Picaud JC, Savagner C, et al. The apparent breastfeeding paradox in very preterm infants: relationship between breast feeding, early weight gain and neurodevelopment based on results from two cohorts. EPIPAGE and LIFT. BMJ Open. 2012;2:e000834.

  104. 104.

    Koo W, Tank S, Martin S, Shi R. Human milk and neurodevelopment in children with very low birth weight: a systematic review. Nutr J. 2014;13:94.

  105. 105.

    Vohr BR, Poindexter BB, Dusick AM, McKinley LT, Higgins RD, Langer JC, et al. Persistent beneficial effects of breast milk ingested in the neonatal intensive care unit on outcomes of extremely low birth weight infants at 30 months of age. Pediatrics. 2007;120:e953–9.

  106. 106.

    Smith MM, Durkin M, Hinton VJ, Bellinger D, Kuhn L. Influence of breastfeeding on cognitive outcomes at age 6–8 years: follow-up of very low birth weight infants. Am J Epidemiol. 2003;158:1075–82.

  107. 107.

    Belfort MB, Anderson PJ, Nowak V, Lee KJ, Molesworth C, Thompson DK, et al. A breast milk feeding, brain development, and neurocognitive outcomes: a 7-year longitudinal study in infants born at less than 30 weeks' gestation. J Pediatr. 2016;177:133–139e1.

  108. 108.

    Patra K, Hamilton M, Johnson TJ, Greene M, Dabrowski E, Meier PP, et al. NICU human milk dose and 20 month neurodevelopmental outcome in very low birth weight infants. Neonatology. 2017;112:330–6.

  109. 109.

    Perrin MT, Pawlak R, Dean LL. A cross-sectional study of fatty acids and brain derived neurotrophic factor (BDNF) in human milk from lactating women following vegan, vegetarian, and omnivore diets. Eur J Nutr. 2018;58:1–10.

  110. 110.

    Wang B. Molecular determinants of milk lactoferrin as a bioactive compound in early neurodevelopment and cognition. J Pediatr. 2016;173:S29–36.

  111. 111.

    Jacobi-Polishook T, Collins CT, Sullivan TR, Simmer K, Gillman MW, Gibson RA, et al. Human milk intake in preterm infants and neurodevelopment at 18 months corrected age. Pediatr Res. 2016;80:486–92.

  112. 112.

    Pinelli J, Saigal S, Atkinson SA. Effect of breastmilk consumption on neurodevelopmental outcomes at 6 and 12 months of age in VLBW infants. Adv Neonatal Care. 2003;3:76–87.

  113. 113.

    Wang Q, Cui Q, Yan C. The effect of supplementation of long-chain polyunsaturated fatty acids during lactation on neurodevelopmental outcomes of preterm infant from infancy to school age: a systematic review and meta-analysis. Pediatr Neurol. 2016;59:54–61.

  114. 114.

    Sammallahti S, Kajantie E, Matinolli HM. Nutrition after preterm birth and adult neurocognitive outcomes. PLoS One. 2017;12:e0185632.

  115. 115.

    Lucas A, Fewtrell MS, Morley R, Lucas PJ, Baker BA, Lister G, et al. Randomized outcome trial of human milk fortification and developmental outcome in preterm infants. Am J Clin Nutr. 1996;64:142–51.

  116. 116.

    O’Connor DL, Jacobs J, Hall R, Adamkin D, Auestad N, Castillo M, et al. Growth and development of premature infants fed predominantly human milk, predominantly premature infant formula, or a combination of human milk and premature formula. J Pediatr Gastroenterol Nutr. 2003;37:437–46.

  117. 117.

    Wendy A. On mammary stem cells. J Cell Sci. 2005;118:3585–94.

  118. 118.

    Shipitsin M, Campbell LL, Argani P, Weremowicz S, Bloushtain-Qimron N, Yao J, et al. Molecular definition of breast tumor heterogeneity. Cancer Cell. 2007;11:259–73.

  119. 119.

    Park SY, Jeong AJ, Kim GY, Jo A, Lee JE, Leem SH, et al. Lactoferrin protects human mesenchymal stem cells from oxidative stress-induced senescence and apoptosis. Microb Biotechnol. 2017;27:1877–84.

  120. 120.

    Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.

  121. 121.

    Caporali A, Emanueli C. MicroRNA regulation in angiogenesis. Vasc Pharmacol. 2011;55:79–86.

  122. 122.

    International Human Genome Sequencing Consortium. Finishing the euchromatic sequence of the human genome. Nature. 2004;431:931–45.

  123. 123.

    Ventura A, Young AG, Winslow MM, Lintault L, Meissner A, Erkeland SJ, et al. Targeted deletion reveals essential and overlapping functions of the miR-17-92 family of mRNA clusters. Cell. 2008;132:875–86.

  124. 124.

    Kosaka N, Izumi H, Seckine K, Ochiya T. MicroRNA as a new immune-regulatory agent in breast milk. Silence. 2010;1:7.

  125. 125.

    Zhou Q, Li M, Wang X, Li Q, Wang T, Zhu Q, et al. Immune-related microRNAs are abundant in breast milk exosomes. Int J Biol Sci. 2012;8:118–23.

  126. 126.

    Alsaweed M, Hartmann P, Geddes D, Foteini K. MicroRNAs in breastmilk and the lactating breast: potential immunoprotectors and developmental regulators for the infant and the mother. Int J Environ Res Public Health. 2015;12:13981–4020.

  127. 127.

    Valadi H, Ekstrom K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO. Exosome-mediated transfer of mRNAs is a novel mechanism of genetic exchange between cells. Nat Cells Biol. 2007;9:654–9.

  128. 128.

    Gu Y, Li M, Wang T, Liang Y, Zhong Z, Wang X, et al. Lactation-related microRNA expression profiles of porcine breast milk exosomes. PLoS One. 2012;7:e43591.

  129. 129.

    Admyre C, Johansson SM, Qazi KR, Filén JJ, Lahesmaa R, Norman M, et al. Exosomes with immune modulatory features are present in human breast milk. J Immun. 2007;179:1969–78.

  130. 130.

    Piskorska-Jasiulewicz MM, Witkowska-Zimny M. Non-nutritional use of breast milk. Postepy Hig Med Dosw (Online). 2017;71:860–6.

Download references

Author information

VF, DGP, and FB conceptualized the structure of the review. FB provided the literature update and wrote the initial version of the manuscript. VF and DGB critically revised, modified, and approved the work. Finally, all authors approved the final version of the manuscript.

Correspondence to Flaminia Bardanzellu.

Ethics declarations

Conflict of Interest

Flaminia Bardanzellu, Diego Giampietro Peroni, and Vassilios Fanos declare they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Bardanzellu, F., Peroni, D.G. & Fanos, V. Human Breast Milk: Bioactive Components, from Stem Cells to Health Outcomes. Curr Nutr Rep (2020).

Download citation


  • Breastfeeding
  • Colostrum
  • Growth factors
  • Stem cells
  • Neonatal outcome
  • Regenerative medicine