Innate immunity and breast milk

Frontiers in Immunology

Volumn 8, Issue MAY, 2017, Pages

  Cacho, Nicole Theresa ^a   Lawrence, Robert M ^a  

^a UNIVERSITY OF FLORIDA COLLEGE OF MEDICINE   (United States)

Author keywords

Breast milk; Colostrum; Human milk; Innate immunity; Preterm

Indexed keywords

GANGLIOSIDE; GLYCOPROTEIN; MUCIN 1; MUCIN 4; OLIGOSACCHARIDE;

ANTIGEN RECOGNITION; BREAST MILK; CELL INTERACTION; CHILD DEVELOPMENT; ENTEROCOCCUS; FETOPLACENTAL UNIT; HUMAN; IMMUNE DEFICIENCY; INFLAMMATION; INNATE IMMUNITY; INTESTINE FLORA; LACTATION DISORDER; LACTOBACILLUS; LYMPHOID TISSUE; NONHUMAN; NUTRITION; PREMATURITY; PROPIONIBACTERIUM; REVIEW; ROTHIA; STAPHYLOCOCCUS; STEM CELL; STREPTOCOCCUS;

EID: 85019980477     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2017.00584     Document Type: Review

References (103)

1. Medzhitov R, Janeway C Jr. Innate immunity. N Engl J Med (2000) 343(5):338-44. doi:10.1056/NEJM200008033430506
2. Newburg DS, Walker WA. Protection of the neonate by the innate immune system of developing gut and of human milk. Pediatr Res (2007) 61(1):2-8. doi:10.1203/01.pdr.0000250274.68571.18
3. Andreas NJ, Kampmann B, Mehring Le-Doare K. Human breast milk: a review on its composition and bioactivity. Early Hum Dev (2015) 91(11):629-35. doi:10.1016/j.earlhumdev.2015.08.013
4. Bahl R, Frost C, Kirkwood BR, Edmond K, Martines J, Bhandari N, et al. Infant feeding patterns and risks of death and hospitalization in the first half of infancy: multicentre cohort study. Bull World Health Organ (2005) 83(6):418-26. doi:10.1590/S0042-96862005000600009
5. Duijts L, Jaddoe VW, Hofman A, Moll HA. Prolonged and exclusive breastfeeding reduces the risk of infectious diseases in infancy. Pediatrics (2010) 126(1):e18-25. doi:10.1542/peds.2008-3256
6. Edmond KM, Zandoh C, Quigley MA, Amenga-Etego S, Owusu-Agyei S, Kirkwood BR. Delayed breastfeeding initiation increases risk of neonatal mortality. Pediatrics (2006) 117(3):e380-6. doi:10.1542/peds.2005-1496
7. Ip S, Chung M, Raman G, Chew P, Magula N, DeVine D, et al. Breastfeeding and maternal and infant health outcomes in developed countries. Evid Rep Technol Assess (Full Rep) (2007) 153:1-186.
8. Kramer MS, Kakuma R. Optimal duration of exclusive breastfeeding. Cochrane Database Syst Rev (2012) 8:CD003517. doi:10.1002/14651858.CD003517.pub2
9. Gartner LM, Morton J, Lawrence RA, Naylor AJ, O'Hare D, Schanler RJ, et al. Breastfeeding and the use of human milk. Pediatrics (2012) 129:e827-41. doi:10.1542/peds.2011-3552
10. Iwasaki A, Medzhitov R. Control of adaptive immunity by the innate immune system. Nat Immunol (2015) 16(4):343-53. doi:10.1038/ni.3123
11. Pacheco AR, Barile D, Underwood MA, Mills DA. The impact of the milk glycobiome on the neonate gut microbiota. Annu Rev Anim Biosci (2015) 3:419-45. doi:10.1146/annurev-animal-022114-111112
12. McGuire MK, McGuire MA. Human milk: mother nature's prototypical probiotic food? Adv Nutr (2015) 6(1):112-23. doi:10.3945/an.114.007435
13. Alexander KL, Targan SR, Elson CO III. Microbiota activation and regulation of innate and adaptive immunity. Immunol Rev (2014) 260(1):206-20. doi:10.1111/imr.12180
14. Mandal SM, Bharti R, Porto WF, Gauri SS, Mandal M, Franco OL, et al. Identification of multifunctional peptides from human milk. Peptides (2014) 56:84-93. doi:10.1016/j.peptides.2014.03.017
15. Chirico G, Marzollo R, Cortinovis S, Fonte C, Gasparoni A. Anti infective properties of human milk. J Nutr (2008) 138(9):1801S-6S.
16. De Leoz ML, Kalanetra KM, Bokulich NA, Strum JS, Underwood MA, German JB, et al. Human milk glycomics and gut microbial genomics in infant feces show a correlation between human milk oligosaccharides and gut microbiota: a proof-of-concept study. J Proteome Res (2015) 14(1):491-502. doi:10.1021/pr500759e
17. Qian L, Zhao A, Zhang Y, Chen T, Zeisel SH, Jia W, et al. Metabolomic approaches to explore chemical diversity of human breast-milk, formula milk and bovine milk. Int J Mol Sci (2016) 17(12):E2128. doi:10.3390/ijms17122128
18. Roncada P, Stipetic LH, Bonizzi L, Burchmore RJ, Kennedy MW. Proteomics as a tool to explore human milk in health and disease. J Proteomics (2013) 88:47-57. doi:10.1016/j.jprot.2013.04.008
19. Liu B, Newburg DS. Human milk glycoproteins protect infants against human pathogens. Breastfeed Med (2013) 8(4):354-62. doi:10.1089/bfm.2013.0016
20. Reuel NF, Mu B, Zhang J, Hinckley A, Strano MS. Nanoengineered glycan sensors enabling native glycoprofiling for medicinal applications: towards profiling glycoproteins without labeling or liberation steps. Chem Soc Rev (2012) 41(17):5744-79. doi:10.1039/c2cs35142k
21. Riskin A, Almog M, Peri R, Halasz K, Srugo I, Kessel A. Changes in immunomodulatory constituents of human milk in response to active infection in the nursing infant. Pediatr Res (2012) 71(2):220-5. doi:10.1038/pr.2011.34
22. Legrand D. Overview of lactoferrin as a natural immune modulator. J Pediatr (2016) 173(Suppl):S10-5. doi:10.1016/j.jpeds.2016.02.071
23. Yin C, Wong JH, Ng TB. Recent studies on the antimicrobial peptides lactoferricin and lactoferrampin. Curr Mol Med (2014) 14(9):1139-54. doi:10.2174/1566524014666141015151749
24. Jakaitis BM, Denning PW. Human breast milk and the gastrointestinal innate immune system. Clin Perinatol (2014) 41(2):423-35. doi:10.1016/j.clp.2014.02.011
25. Anderson RC, Dalziel JE, Gopal PK, Bassett S, Ellis A, Roy NC. The role of intestinal barrier function in early life in the development of colitis. In: Fukata M, editor. Colitis. Rijeka: InTechOpen (2012). p. 3-30.
26. Nussbaum C, Gloning A, Pruenster M, Frommhold D, Bierschenk S, Genzel-Boroviczeny O, et al. Neutrophil and endothelial adhesive function during human fetal ontogeny. J Leukoc Biol (2013) 93(2):175-84. doi:10.1189/jlb.0912468
27. Bode L, McGuire M, Rodriguez JM, Geddes DT, Hassiotou F, Hartmann PE, et al. It's alive: microbes and cells in human milk and their potential benefits to mother and infant. Adv Nutr (2014) 5(5):571-3. doi:10.3945/an.114.006643
28. Hassiotou F, Geddes D. Anatomy of the human mammary gland: current status of knowledge. Clin Anat (2013) 26(1):29-48. doi:10.1002/ca.22165
29. 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(10):2164-74. doi:10.1002/stem.1188
30. Hassiotou F, Geddes DT, Hartmann PE. Cells in human milk: state of the science. J Hum Lact (2013) 29(2):171-82. doi:10.1177/0890334413477242
31. Ballard O, Morrow AL. Human milk composition: nutrients and bioactive factors. Pediatr Clin North Am (2013) 60(1):49-74. doi:10.1016/j.pcl.2012.10.002
32. Hassiotou F, Geddes DT. Immune cell-mediated protection of the mammary gland and the infant during breastfeeding. Adv Nutr (2015) 6(3):267-75. doi:10.3945/an.114.007377
33. Hassiotou F, Hepworth AR, Metzger P, Tat Lai C, Trengove N, Hartmann PE, et al. Maternal and infant infections stimulate a rapid leukocyte response in breastmilk. Clin Transl Immunol (2013) 2(4):e3. doi:10.1038/cti.2013.1
34. Jimenez E, de Andres J, Manrique M, Pareja-Tobes P, Tobes R, Martinez-Blanch JF, et al. Metagenomic analysis of milk of healthy and mastitis-suffering women. J Hum Lact (2015) 31(3):406-15. doi:10.1177/0890334415585078
35. Bryan DL, Hart PH, Forsyth KD, Gibson RA. Immunomodulatory constituents of human milk change in response to infant bronchiolitis. Pediatr Allergy Immunol (2007) 18(6):495-502. doi:10.1111/j.1399-3038.2007.00565.x
36. Hassiotou F, Heath B, Ocal O, Filgueira L, Geddes DT, Hartmann PE, et al. Breastmilk stem cells transfer from mother to neonatal organs. FASEB J (2014) 28(1):Suppl 216.4. Exp Biol (2014), San Diego, CA.
37. Heikkila MP, Saris PE. Inhibition of Staphylococcus aureus by the commensal bacteria of human milk. J Appl Microbiol (2003) 95(3):471-8. doi:10.1046/j.1365-2672.2003.02002.x
38. Solis G, de Los Reyes-Gavilan CG, Fernandez N, Margolles A, Gueimonde M.Establishment and development of lactic acid bacteria and bifidobacteria microbiota in breast-milk and the infant gut. Anaerobe (2010) 16(3):307-10. doi:10.1016/j.anaerobe.2010.02.004
39. Arboleya S, Ruas-Madiedo P, Margolles A, Solis G, Salminen S, de Los Reyes-Gavilan CG, et al. Characterization and in vitro properties of potentially probiotic Bifidobacterium strains isolated from breast-milk. Int J Food Microbiol (2011) 149(1):28-36. doi:10.1016/j.ijfoodmicro.2010.10.036
40. Martin V, Maldonado-Barragan A, Moles L, Rodriguez-Banos M, Campo RD, Fernandez L, et al. Sharing of bacterial strains between breast milk and infant feces. J Hum Lact (2012) 28(1):36-44. doi:10.1177/0890334411424729
41. Jost T, Lacroix C, Braegger C, Chassard C. Assessment of bacterial diversity in breast milk using culture-dependent and culture-independent approaches. Br J Nutr (2013) 110(7):1253-62. doi:10.1017/S0007114513000597
42. Gomez-Gallego C, Garcia-Mantrana I, Salminen S, Collado MC. The human milk microbiome and factors influencing its composition and activity. Semin Fetal Neonatal Med (2016) 21(6):400-5. doi:10.1016/j.siny.2016.05.003
43. Fitzstevens JL, Smith KC, Hagadorn JI, Caimano MJ, Matson AP, Brownell EA. Systematic review of the human milk microbiota. Nutr Clin Pract (2016) 1-11. doi:10.1177/0884533616670150
44. Cacho N, Neu J. Manipulation of the intestinal microbiome in newborn infants. Adv Nutr (2014) 5(1):114-8. doi:10.3945/an.113.004820
45. Hunt KM, Foster JA, Forney LJ, Schutte UM, Beck DL, Abdo Z, et al. Characterization of the diversity and temporal stability of bacterial communities in human milk. PLoS One (2011) 6(6):e21313. doi:10.1371/journal.pone.0021313
46. Walker AW, Martin JC, Scott P, Parkhill J, Flint HJ, Scott KP. 16S rRNA gene-based profiling of the human infant gut microbiota is strongly influenced by sample processing and PCR primer choice. Microbiome (2015) 3:26. doi:10.1186/s40168-015-0087-4
47. Backhed F, Roswall J, Peng Y, Feng Q, Jia H, Kovatcheva-Datchary P, et al. Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host Microbe (2015) 17(5):690-703. doi:10.1016/j.chom.2015.05.012
48. Fernandez L, Langa S, Martin V, Maldonado A, Jimenez E, Martin R, et al. The human milk microbiota: origin and potential roles in health and disease. Pharmacol Res (2013) 69(1):1-10. doi:10.1016/j.phrs.2012.09.001
49. Rautava S. Early microbial contact, the breast milk microbiome and child health. J Dev Orig Health Dis (2016) 7(1):5-14. doi:10.1017/S2040174415001233
50. Perez PF, Dore J, Leclerc M, Levenez F, Benyacoub J, Serrant P, et al. Bacterial imprinting of the neonatal immune system: lessons from maternal cells? Pediatrics (2007) 119(3):e724-32. doi:10.1542/peds.2006-1649
51. McGuire MK, McGuire MA. Got bacteria? The astounding, yet not-so-surprising, microbiome of human milk. Curr Opin Biotechnol (2016) 44:63-8. doi:10.1016/j.copbio.2016.11.013
52. Trend S, Strunk T, Hibbert J, Kok CH, Zhang G, Doherty DA, et al. Antimicrobial protein and peptide concentrations and activity in human breast milk consumed by preterm infants at risk of late-onset neonatal sepsis. PLoS One (2015) 10(2):e0117038. doi:10.1371/journal.pone.0117038
53. Nanthakumar NN, Meng D, Newburg DS. Glucocorticoids and microbiota regulate ontogeny of intestinal fucosyltransferase 2 requisite for gut homeostasis. Glycobiology (2013) 23(10):1131-41. doi:10.1093/glycob/cwt050
54. Newburg DS, He Y. Neonatal gut microbiota and human milk glycans cooperate to attenuate infection and inflammation. Clin Obstet Gynecol (2015) 58(4):814-26. doi:10.1097/GRF.0000000000000156
55. Newburg DS, Morelli L. Human milk and infant intestinal mucosal glycans guide succession of the neonatal intestinal microbiota. Pediatr Res (2015) 77(1-2):115-20. doi:10.1038/pr.2014.178
56. He Y, Liu S, Leone S, Newburg DS. Human colostrum oligosaccharides modulate major immunologic pathways of immature human intestine. Mucosal Immunol (2014) 7(6):1326-39. doi:10.1038/mi.2014.20
57. He Y, Liu S, Kling DE, Leone S, Lawlor NT, Huang Y, et al. The human milk oligosaccharide 2'-fucosyllactose modulates CD14 expression in human enterocytes, thereby attenuating LPS-induced inflammation. Gut (2016) 65(1):33-46. doi:10.1136/gutjnl-2014-307544
58. Baldassarre ME, Di Mauro A, Mastromarino P, Fanelli M, Martinelli D, Urbano F, et al. Administration of a multi-strain probiotic product to women in the perinatal period differentially affects the breast milk cytokine profile and may have beneficial effects on neonatal gastrointestinal functional symptoms. A randomized clinical trial. Nutrients (2016) 8(11):E677. doi:10.3390/nu8110677
59. Chatterton DE, Nguyen DN, Bering SB, Sangild PT. Anti-inflammatory mechanisms of bioactive milk proteins in the intestine of newborns. Int J Biochem Cell Biol (2013) 45(8):1730-47. doi:10.1016/j.biocel.2013.04.028
60. He Y, Lawlor NT, Newburg DS. Human milk components modulate toll-like receptor-mediated inflammation. Adv Nutr (2016) 7(1):102-11. doi:10.3945/an.115.010090
61. LeBouder E, Rey-Nores JE, Raby AC, Affolter 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(6):3742-52. doi:10.4049/jimmunol.176.6.3742
62. Goldman AS, Garza C, Nichols BL, Goldblum RM. Immunologic factors in human milk during the first year of lactation. J Pediatr (1982) 100(4):563-7. doi:10.1016/S0022-3476(82)80753-1
63. Lawrence RA, Lawrence RM. Chapter 5: Host-resistance factors and immunologic significance of human milk. In: Lawrence RA, Lawrence RM, editors. Breastfeeding: A Guide for the Medical Profession. Philadelphia, PA: Elsevier (2015). p. 146-93.
64. Gao X, McMahon RJ, Woo JG, Davidson BS, Morrow AL, Zhang Q. Temporal changes in milk proteomes reveal developing milk functions. J Proteome Res (2012) 11(7):3897-907. doi:10.1021/pr3004002
65. Phadke SM, Deslouches B, Hileman SE, Montelaro RC, Wiesenfeld HC, Mietzner TA. Antimicrobial peptides in mucosal secretions: the importance of local secretions in mitigating infection. J Nutr (2005) 135(5):1289-93.
66. Vorbach C, Capecchi MR, Penninger JM. Evolution of the mammary gland from the innate immune system? Bioessays (2006) 28(6):606-16. doi:10.1002/bies.20423
67. Wada Y, Lonnerdal B. Bioactive peptides derived from human milk proteins-mechanisms of action. J Nutr Biochem (2014) 25(5):503-14. doi:10.1016/j.jnutbio.2013.10.012
68. Sokolov AV, Ageeva KV, Pulina MO, Zakharova ET, Vasilyev VB. Effect of lactoferrin on oxidative features of ceruloplasmin. Biometals (2009) 22(3):521-9. doi:10.1007/s10534-009-9209-4
69. Matos C, Ribeiro M, Guerra A. Breastfeeding: antioxidative properties of breast milk. J Appl Biomed (2015) 13:169-80. doi:10.1016/j.jab.2015.04.003
70. Podolsky DK. Mucosal immunity and inflammation. V. Innate mechanisms of mucosal defense and repair: the best offense is a good defense. Am J Physiol (1999) 277(3 Pt 1):G495-9.
71. Barrera GJ, Tortolero GS. Trefoil factor 3 (TFF3) from human breast milk activates PAR-2 receptors, of the intestinal epithelial cells HT-29, regulating cytokines and defensins. Bratisl Lek Listy (2016) 117(6):332-9. doi:10.4149/BLL_2016_066
72. Ronveaux CC, Tome D, Raybould HE. Glucagon-like peptide 1 interacts with ghrelin and leptin to regulate glucose metabolism and food intake through vagal afferent neuron signaling. J Nutr (2015) 145(4):672-80. doi:10.3945/jn.114.206029
73. Schueler J, Alexander B, Hart AM, Austin K, Larson-Meyer DE. Presence and dynamics of leptin, GLP-1, and PYY in human breast milk at early postpartum. Obesity (Silver Spring) (2013) 21(7):1451-8. doi:10.1002/oby.20345
74. Kobata R, Tsukahara H, Ohshima Y, Ohta N, Tokuriki S, Tamura S, et al. High levels of growth factors in human breast milk. Early Hum Dev (2008) 84(1):67-9. doi:10.1016/j.earlhumdev.2007.07.005
75. Ozgurtas T, Aydin I, Turan O, Koc E, Hirfanoglu IM, Acikel CH, et al. Vascular endothelial growth factor, basic fibroblast growth factor, insulin-like growth factor-I and platelet-derived growth factor levels in human milk of mothers with term and preterm neonates. Cytokine (2010) 50(2):192-4. doi:10.1016/j.cyto.2010.02.008
76. 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(2):305-8. doi:10.1016/j.cyto.2012.04.010
77. Burrin DG, Stoll B. Key nutrients and growth factors for the neonatal gastrointestinal tract. Clin Perinatol (2002) 29(1):65-96. doi:10.1016/S0095-5108(03)00065-4
78. Schwartz MZ, Kato Y, Yu D, Lukish JR. Growth-factor enhancement of compromised gut function following massive small-bowel resection. Pediatr Surg Int (2000) 16(3):174-5. doi:10.1007/s003830050716
79. Ohda Y, Hori K, Tomita T, Hida N, Kosaka T, Fukuda Y, et al. Effects of hepatocyte growth factor on rat inflammatory bowel disease models. Dig Dis Sci (2005) 50(5):914-21. doi:10.1007/s10620-005-2664-z
80. Weiss GA, Troxler H, Klinke G, Rogler D, Braegger C, Hersberger M. High levels of anti-inflammatory and pro-resolving lipid mediators lipoxins and resolvins and declining docosahexaenoic acid levels in human milk during the first month of lactation. Lipids Health Dis (2013) 12:89. doi:10.1186/1476-511X-12-89
81. Mehta R, Petrova A. Is variation in total antioxidant capacity of human milk associated with levels of bio-active proteins? J Perinatol (2014) 34(3):220-2. doi:10.1038/jp.2013.151
82. Song BJ, Jouni ZE, Ferruzzi MG. Assessment of phytochemical content in human milk during different stages of lactation. Nutrition (2013) 29(1):195-202. doi:10.1016/j.nut.2012.07.015
83. Szlagatys-Sidorkiewicz A, Zagierski M, Jankowska A, Luczak G, Macur K, Baczek T, et al. Longitudinal study of vitamins A, E and lipid oxidative damage in human milk throughout lactation. Early Hum Dev (2012) 88(6):421-4. doi:10.1016/j.earlhumdev.2011.10.007
84. Tijerina-Saenz A, Innis SM, Kitts DD. Antioxidant capacity of human milk and its association with vitamins A and E and fatty acid composition. Acta Paediatr (2009) 98(11):1793-8. doi:10.1111/j.1651-2227.2009.01437.x
85. Leach JL, Baxter JH, Molitor BE, Ramstack MB, Masor ML. Total potentially available nucleosides of human milk by stage of lactation. Am J Clin Nutr (1995) 61(6):1224-30.
86. Brunser O, Espinoza J, Araya M, Cruchet S, Gil A. Effect of dietary nucleotide supplementation on diarrhoeal disease in infants. Acta Paediatr (1994) 83(2):188-91. doi:10.1111/j.1651-2227.1994.tb13048.x
87. Butte NF, Goldblum RM, Fehl LM, Loftin K, Smith EO, Garza C, et al. Daily ingestion of immunologic components in human milk during the first four months of life. Acta Paediatr Scand (1984) 73(3):296-301. doi:10.1111/j.1651-2227.1994.tb17738.x
88. Tregoat V, Montagne P, Bene MC, Faure G. Changes in the mannan binding lectin (MBL) concentration in human milk during lactation. J Clin Lab Anal (2002) 16(6):304-7. doi:10.1002/jcla.10055
89. van Herwijnen MJ, Zonneveld MI, Goerdayal S, Nolte-'t Hoen EN, Garssen J, Stahl B, et al. Comprehensive proteomic analysis of human milk-derived extracellular vesicles unveils a novel functional proteome distinct from other milk components. Mol Cell Proteomics (2016) 15(11):3412-23. doi:10.1074/mcp.M116.060426
90. Gidrewicz DA, Fenton TR. A systematic review and meta-analysis of the nutrient content of preterm and term breast milk. BMC Pediatr (2014) 14:216. doi:10.1186/1471-2431-14-216
91. Khodayar-Pardo P, Mira-Pascual L, Collado MC, Martinez-Costa C. Impact of lactation stage, gestational age and mode of delivery on breast milk microbiota. J Perinatol (2014) 34(8):599-605. doi:10.1038/jp.2014.47
92. Moles L, Gomez M, Jimenez E, Fernandez L, Bustos G, Chaves F, et al. Preterm infant gut colonization in the neonatal ICU and complete restoration 2 years later. Clin Microbiol Infect (2015) 21(10):936.e1-10. doi:10.1016/j.cmi.2015.06.003
93. Underwood MA, Gaerlan S, De Leoz ML, Dimapasoc L, Kalanetra KM, Lemay DG, et al. Human milk oligosaccharides in premature infants: absorption, excretion, and influence on the intestinal microbiota. Pediatr Res (2015) 78(6):670-7. doi:10.1038/pr.2015.162
94. Stewart CJ, Marrs EC, Nelson A, Lanyon C, Perry JD, Embleton ND, et al. Development of the preterm gut microbiome in twins at risk of necrotising enterocolitis and sepsis. PLoS One (2013) 8(8):e73465. doi:10.1371/journal.pone.0073465
95. Said MB, Hays S, Maucort-Boulch D, Oulmaati A, Hantova S, Loys CM, et al. Gut microbiota in preterm infants with gross blood in stools: a prospective, controlled study. Early Hum Dev (2014) 90(10):579-85. doi:10.1016/j.earlhumdev.2014.07.004
96. Torrazza RM, Ukhanova M, Wang X, Sharma R, Hudak ML, Neu J, et al. Intestinal microbial ecology and environmental factors affecting necrotizing enterocolitis. PLoS One (2013) 8(12):e83304. doi:10.1371/journal.pone.0083304
97. Neu J. Probiotics and necrotizing enterocolitis. Clin Perinatol (2014) 41(4):967-78. doi:10.1016/j.clp.2014.08.014
98. Fituch CC, Palkowetz KH, Goldman AS, Schanler RJ. Concentrations of IL-10 in preterm human milk and in milk from mothers of infants with necrotizing enterocolitis. Acta Paediatr (2004) 93(11):1496-500. doi:10.1111/j.1651-2227.2004.tb02636.x
99. Trend S, Strunk T, Lloyd ML, Kok CH, Metcalfe J, Geddes DT, et al. Levels of innate immune factors in preterm and term mothers' breast milk during the 1st month postpartum. Br J Nutr (2016) 115(7):1178-93. doi:10.1017/S0007114516000234
100. 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(6):1181-7. doi:10.3945/jn.110.133652
101. Maheshwari A, Kelly DR, Nicola T, Ambalavanan N, Jain SK, Murphy-Ullrich J, et al. TGF-beta2 suppresses macrophage cytokine production and mucosal inflammatory responses in the developing intestine. Gastroenterology (2011) 140(1):242-53. doi:10.1053/j.gastro.2010.09.043
102. Wang XF, Cao RM, Li J, Wu J, Wu SM, Chen TX. Identification of sociodemographic and clinical factors associated with the levels of human beta-defensin-1 and human beta-defensin-2 in the human milk of Han Chinese. Br J Nutr (2014) 111(5):867-74. doi:10.1017/S0007114513003292
103. Armogida SA, Yannaras NM, Melton AL, Srivastava MD. Identification and quantification of innate immune system mediators in human breast milk. Allergy Asthma Proc (2004) 25(5):297-304.