Mother's Milk: A Purposeful Contribution to the Development of the Infant Microbiota and Immunity

Kirsty Le Doare, Beth Holder, Aisha Bassett, Pia S Pannaraj, Kirsty Le Doare, Beth Holder, Aisha Bassett, Pia S Pannaraj

Abstract

Breast milk is the perfect nutrition for infants, a result of millions of years of evolution. In addition to providing a source of nutrition, breast milk contains a diverse array of microbiota and myriad biologically active components that are thought to guide the infant's developing mucosal immune system. It is believed that bacteria from the mother's intestine may translocate to breast milk and dynamically transfer to the infant. Such interplay between mother and her infant is a key to establishing a healthy infant intestinal microbiome. These intestinal bacteria protect against many respiratory and diarrheal illnesses, but are subject to environmental stresses such as antibiotic use. Orchestrating the development of the microbiota are the human milk oligosaccharides (HMOs), the synthesis of which are partially determined by the maternal genotype. HMOs are thought to play a role in preventing pathogenic bacterial adhesion though multiple mechanisms, while also providing nutrition for the microbiome. Extracellular vesicles (EVs), including exosomes, carry a diverse cargo, including mRNA, miRNA, and cytosolic and membrane-bound proteins, and are readily detectable in human breast milk. Strongly implicated in cell-cell signaling, EVs could therefore may play a further role in the development of the infant microbiome. This review considers the emerging role of breast milk microbiota, bioactive HMOs, and EVs in the establishment of the neonatal microbiome and the consequent potential for modulation of neonatal immune system development.

Keywords: breast milk; breast milk microbiome; exosomes; extracellular vesicles; human milk oligosaccharides; infant microbiome; microbiome; microbiota.

Figures

Figure 1
Figure 1
Factors that influence maternal breast milk microbiome and proposed mechanism of how breast milk may alter the infant gut microbiome and health outcome. A myriad of environmental, genetic, and immune factors personalize a mother’s milk for delivery to her infant. Starting from the initial feeding, the breast milk microbes and human milk oligosaccharides contribute to the composition and diversity of the infant gut microbiome. The initial gut microbes may continue to promote colonization of a healthy community or an aberrant community. During the critical window of immune development, the community types may induce metabolic alterations leading to differing immune phenotypes and long-term health outcomes. SCFA, short-chain fatty acids.
Figure 2
Figure 2
Mechanism of action of HMO to prevent aberrant pathogen colonization. HMO may bind directly to bacteria in the gut lumen causing conformational change in bacterial binding sites and preventing binding to cell receptors; alternatively, HMO may bind directly to gut epithelial cells causing altered expression of cell receptors, which prevent pathogen binding to gut epithelial cells. HMO, human milk oligosaccharide.

References

    1. American Academy of Pediatrics Section on Breastfeeding. Breastfeeding and the use of human milk. Pediatrics (2012) 129(3):e827–41.10.1542/peds.2011-3552
    1. Klopp A, Vehling L, Becker AB, Subbarao P, Mandhane PJ, Turvey SE, et al. Modes of infant feeding and the risk of childhood asthma: a prospective birth cohort study. J Pediatr (2017) 190:192–9.e2.10.1016/j.jpeds.2017.07.012
    1. Dogaru CM, Nyffenegger D, Pescatore AM, Spycher BD, Kuehni CE. Breastfeeding and childhood asthma: systematic review and meta-analysis. Am J Epidemiol (2014) 179(10):1153–67.10.1093/aje/kwu072
    1. den Dekker HT, Sonnenschein-van der Voort AM, Jaddoe VW, Reiss IK, de Jongste JC, Duijts L. Breastfeeding and asthma outcomes at the age of 6 years: the Generation R Study. Pediatr Allergy Immunol (2016) 27(5):486–92.10.1111/pai.12576
    1. Azad MB, Vehling L, Lu Z, Dai D, Subbarao P, Becker AB, et al. Breastfeeding, maternal asthma and wheezing in the first year of life: a longitudinal birth cohort study. Eur Respir J (2017) 49(5).10.1183/13993003.02019-2016
    1. Horta BL, Loret de Mola C, Victora CG. Long-term consequences of breastfeeding on cholesterol, obesity, systolic blood pressure and type 2 diabetes: a systematic review and meta-analysis. Acta Paediatr (2015) 104(467):30–7.10.1111/apa.13133
    1. Xu L, Lochhead P, Ko Y, Claggett B, Leong RW, Ananthakrishnan AN. Systematic review with meta-analysis: breastfeeding and the risk of Crohn’s disease and ulcerative colitis. Aliment Pharmacol Ther (2017) 46(9):780–9.10.1111/apt.14291
    1. Victora CG, Bahl R, Barros AJ, França GV, Horton S, Krasevec J, et al. Breastfeeding in the 21st century: epidemiology, mechanisms, and lifelong effect. Lancet (2016) 387(10017):475–90.10.1016/S0140-6736(15)01024-7
    1. Kramer MS, Aboud F, Mironova E, Vanilovich I, Platt RW, Matush L, et al. Breastfeeding and child cognitive development: new evidence from a large randomized trial. Arch Gen Psychiatry (2008) 65(5):578–84.10.1001/archpsyc.65.5.578
    1. Brandtzaeg P. The mucosal immune system and its integration with the mammary glands. J Pediatr (2010) 156(2 Suppl):S8–15.10.1016/j.jpeds.2009.11.014
    1. Piper KM, Berry CA, Cregan MD. The bioactive nature of human breastmilk. Breastfeed Rev (2007) 15(3):5–10.
    1. Hanson LA, Korotkova M, Lundin S, Håversen L, Silfverdal SA, Mattsby-Baltzer I, et al. The transfer of immunity from mother to child. Ann N Y Acad Sci (2003) 987:199–206.10.1111/j.1749-6632.2003.tb06049.x
    1. Walker WA, Iyengar RS. Breast milk, microbiota, and intestinal immune homeostasis. Pediatr Res (2015) 77(1–2):220–8.10.1038/pr.2014.160
    1. Mueller NT, Bakacs E, Combellick J, Grigoryan Z, Dominguez-Bello MG. The infant microbiome development: mom matters. Trends Mol Med (2015) 21(2):109–17.10.1016/j.molmed.2014.12.002
    1. Ballard O, Morrow AL. Human milk composition: nutrients and bioactive factors. Pediatr Clin North Am (2013) 60(1):49–74.10.1016/j.pcl.2012.10.002
    1. 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) 8:696.10.3389/fimmu.2017.00696
    1. Andreas NJ, Kampmann B, Mehring Le-Doare K. Human breast milk: a review on its composition and bioactivity. Early Hum Dev (2015) 91(11):629–35.10.1016/j.earlhumdev.2015.08.013
    1. Cabrera-Rubio R, Collado MC, Laitinen K, Salminen S, Isolauri E, Mira A. The human milk microbiome changes over lactation and is shaped by maternal weight and mode of delivery. Am J Clin Nutr (2012) 96(3):544–51.10.3945/ajcn.112.037382
    1. Jeurink PV, van Bergenhenegouwen J, Jiménez E, Knippels LM, Fernández L, Garssen J, et al. Human milk: a source of more life than we imagine. Benef Microbes (2013) 4(1):17–30.10.3920/BM2012.0040
    1. Heikkila MP, Saris PE. Inhibition of Staphylococcus aureus by the commensal bacteria of human milk. J Appl Microbiol (2003) 95(3):471–8.10.1046/j.1365-2672.2003.02002.x
    1. Dominguez-Bello MG, Costello EK, Contreras M, Magris M, Hidalgo G, Fierer N, et al. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci U S A (2010) 107(26):11971–5.10.1073/pnas.1002601107
    1. Gritz EC, Bhandari V. The human neonatal gut microbiome: a brief review. Front Pediatr (2015) 3:17.10.3389/fped.2015.00017
    1. Pannaraj P, Li F, Cerini C, Bender J, Yang S, Rollie A, et al. Association between breast milk bacterial communities and establishment and development of the infant gut microbiome. JAMA Pediatr (2017) 171(7):647–54.10.1001/jamapediatrics.2017.0378
    1. Azad MB, Konya T, Maughan H, Guttman DS, Field CJ, Chari RS, et al. Gut microbiota of healthy Canadian infants: profiles by mode of delivery and infant diet at 4 months. CMAJ (2013) 185(5):385–94.10.1503/cmaj.121189
    1. Bergström A, Skov TH, Bahl MI, Roager HM, Christensen LB, Ejlerskov KT, et al. Establishment of intestinal microbiota during early life: a longitudinal, explorative study of a large cohort of Danish infants. Appl Environ Microbiol (2014) 80(9):2889–900.10.1128/AEM.00342-14
    1. Gomez-Llorente C, Plaza-Diaz J, Aguilera M, Muñoz-Quezada S, Bermudez-Brito M, Peso-Echarri P, et al. Three main factors define changes in fecal microbiota associated with feeding modality in infants. J Pediatr Gastroenterol Nutr (2013) 57(4):461–6.10.1097/MPG.0b013e31829d519a
    1. Jost T, Lacroix C, Braegger C, Rochat F, Chassard C. Vertical mother-neonate transfer of maternal gut bacteria via breastfeeding. Environ Microbiol (2014) 16(9):2891–904.10.1111/1462-2920.12238
    1. Fernández L, Langa S, Martín V, Maldonado A, Jiménez E, Martín R, et al. The human milk microbiota: origin and potential roles in health and disease. Pharmacol Res (2013) 69(1):1–10.10.1016/j.phrs.2012.09.001
    1. Boix-Amorós A, Collado MC, Mira A. Relationship between milk microbiota, bacterial load, macronutrients, and human cells during lactation. Front Microbiol (2016) 7:492.10.3389/fmicb.2016.00492
    1. Martín V, Maldonado-Barragán A, Moles L, Rodriguez-Baños M, Campo RD, Fernández L, et al. Sharing of bacterial strains between breast milk and infant feces. J Hum Lact (2012) 28(1):36–44.10.1177/0890334411424729
    1. Makino H, Kushiro A, Ishikawa E, Muylaert D, Kubota H, Sakai T, et al. Transmission of intestinal Bifidobacterium longum subsp. longum strains from mother to infant, determined by multilocus sequencing typing and amplified fragment length polymorphism. Appl Environ Microbiol (2011) 77(19):6788–93.10.1128/AEM.05346-11
    1. Benito D, Lozano C, Jiménez E, Albújar M, Gómez A, Rodríguez JM, et al. Characterization of Staphylococcus aureus strains isolated from faeces of healthy neonates and potential mother-to-infant microbial transmission through breastfeeding. FEMS Microbiol Ecol (2015) 91(3).10.1093/femsec/fiv007
    1. Martín R, Heilig HG, Zoetendal EG, Jiménez E, Fernández L, Smidt H, et al. Cultivation-independent assessment of the bacterial diversity of breast milk among healthy women. Res Microbiol (2007) 158(1):31–7.10.1016/j.resmic.2006.11.004
    1. Collado MC, Delgado S, Maldonado A, Rodríguez JM. Assessment of the bacterial diversity of breast milk of healthy women by quantitative real-time PCR. Lett Appl Microbiol (2009) 48(5):523–8.10.1111/j.1472-765X.2009.02567.x
    1. Hunt KM, Foster JA, Forney LJ, Schütte 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):e21313.10.1371/journal.pone.0021313
    1. Fitzstevens JL, Smith KC, Hagadorn JI, Caimano MJ, Matson AP, Brownell EA. Systematic review of the human milk microbiota. Nutr Clin Pract (2017) 32(3):354–64.10.1177/0884533616670150
    1. Urbaniak C, Gloor GB, Brackstone M, Scott L, Tangney M, Reid G. The microbiota of breast tissue and its association with breast cancer. Appl Environ Microbiol (2016) 82(16):5039–48.10.1128/AEM.01235-16
    1. Ramsay DT, Kent JC, Owens RA, Hartmann PE. Ultrasound imaging of milk ejection in the breast of lactating women. Pediatrics (2004) 113(2):361–7.10.1542/peds.113.2.361
    1. Biagi E, Quercia S, Aceti A, Beghetti I, Rampelli S, Turroni S, et al. The bacterial ecosystem of mother’s milk and infant’s mouth and gut. Front Microbiol (2017) 8:1214.10.3389/fmicb.2017.01214
    1. Bender JM, Li F, Martelly S, Byrt E, Rouzier V, Leo M, et al. Maternal HIV infection influences the microbiome of HIV-uninfected infants. Sci Transl Med (2016) 8(349):349ra100.10.1126/scitranslmed.aaf5103
    1. Rodriguez JM. The origin of human milk bacteria: is there a bacterial entero-mammary pathway during late pregnancy and lactation? Adv Nutr (2014) 5(6):779–84.10.3945/an.114.007229
    1. Perez PF, Doré 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):e724–32.10.1542/peds.2006-1649
    1. Cabrera-Rubio R, Mira-Pascual L, Mira A, Collado MC. Impact of mode of delivery on the milk microbiota composition of healthy women. J Dev Orig Health Dis (2016) 7(1):54–60.10.1017/S2040174415001397
    1. 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):599–605.10.1038/jp.2014.47
    1. Urbaniak C, Angelini M, Gloor GB, Reid G. Human milk microbiota profiles in relation to birthing method, gestation and infant gender. Microbiome (2016) 4(1):1.10.1186/s40168-015-0145-y
    1. Kumar H, du Toit E, Kulkarni A, Aakko J, Linderborg KM, Zhang Y, et al. Distinct patterns in human milk microbiota and fatty acid profiles across specific geographic locations. Front Microbiol (2016) 7:1619.10.3389/fmicb.2016.01619
    1. Olivares M, Albrecht S, De Palma G, Ferrer MD, Castillejo G, Schols HA, et al. Human milk composition differs in healthy mothers and mothers with celiac disease. Eur J Nutr (2015) 54(1):119–28.10.1007/s00394-014-0692-1
    1. Gonzalez R, Maldonado A, Martin V, Mandomando I, Fumado V, Metzner KJ, et al. Breast milk and gut microbiota in African mothers and infants from an area of high HIV prevalence. PLoS One (2013) 8(11):e80299.10.1371/journal.pone.0080299
    1. Sitarik AR, Bobbitt KR, Havstad SL, Fujimura KE, Levin AM, Zoratti EM, et al. Breast milk transforming growth factor beta is associated with neonatal gut microbial composition. J Pediatr Gastroenterol Nutr (2017) 65(3):e60–7.10.1097/MPG.0000000000001585
    1. Soto A, Martin V, Jimenez E, Mader I, Rodriguez JM, Fernandez L. Lactobacilli and bifidobacteria in human breast milk: influence of antibiotherapy and other host and clinical factors. J Pediatr Gastroenterol Nutr (2014) 59(1):78–88.10.1097/MPG.0000000000000347
    1. Urbaniak C, McMillan A, Angelini M, Gloor GB, Sumarah M, Burton JP, et al. Effect of chemotherapy on the microbiota and metabolome of human milk, a case report. Microbiome (2014) 2:24.10.1186/2049-2618-2-24
    1. Jara S, Sanchez M, Vera R, Cofre J, Castro E. The inhibitory activity of Lactobacillus spp. isolated from breast milk on gastrointestinal pathogenic bacteria of nosocomial origin. Anaerobe (2011) 17(6):474–7.10.1016/j.anaerobe.2011.07.008
    1. Olivares M, Diaz-Ropero MP, Martin R, Rodriguez JM, Xaus J. Antimicrobial potential of four Lactobacillus strains isolated from breast milk. J Appl Microbiol (2006) 101(1):72–9.10.1111/j.1365-2672.2006.02981.x
    1. Lyons A, O’Mahony D, O’Brien F, MacSharry J, Sheil B, Ceddia M, et al. Bacterial strain-specific induction of Foxp3+ T regulatory cells is protective in murine allergy models. Clin Exp Allergy (2010) 40(5):811–9.10.1111/j.1365-2222.2009.03437.x
    1. Maldonado J, Canabate F, Sempere L, Vela F, Sanchez AR, Narbona E, et al. Human milk probiotic Lactobacillus fermentum CECT5716 reduces the incidence of gastrointestinal and upper respiratory tract infections in infants. J Pediatr Gastroenterol Nutr (2012) 54(1):55–61.10.1097/MPG.0b013e3182333f18
    1. Beasley SS, Saris PE. Nisin-producing Lactococcus lactis strains isolated from human milk. Appl Environ Microbiol (2004) 70(8):5051–3.10.1128/AEM.70.8.5051-5053.2004
    1. Arrieta MC, Stiemsma LT, Amenyogbe N, Brown EM, Finlay B. The intestinal microbiome in early life: health and disease. Front Immunol (2014) 5:427.10.3389/fimmu.2014.00427
    1. Gensollen T, Iyer SS, Kasper DL, Blumberg RS. How colonization by microbiota in early life shapes the immune system. Science (2016) 352(6285):539–44.10.1126/science.aad9378
    1. Macpherson AJ, Harris NL. Interactions between commensal intestinal bacteria and the immune system. Nat Rev Immunol (2004) 4(6):478–85.10.1038/nri1373
    1. Mazmanian SK, Liu CH, Tzianabos AO, Kasper DL. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell (2005) 122(1):107–18.10.1016/j.cell.2005.05.007
    1. Diaz-Ropero MP, Martin R, Sierra S, Lara-Villoslada F, Rodriguez JM, Xaus J, et al. Two Lactobacillus strains, isolated from breast milk, differently modulate the immune response. J Appl Microbiol (2007) 102(2):337–43.10.1111/j.1365-2672.2006.03102.x
    1. Pabst HF, Spady DW, Pilarski LM, Carson MM, Beeler JA, Krezolek MP. Differential modulation of the immune response by breast- or formula-feeding of infants. Acta Paediatr (1997) 86(12):1291–7.10.1111/j.1651-2227.1997.tb14900.x
    1. Perez-Cano FJ, Dong H, Yaqoob P. In vitro immunomodulatory activity of Lactobacillus fermentum CECT5716 and Lactobacillus salivarius CECT5713: two probiotic strains isolated from human breast milk. Immunobiology (2010) 215(12):996–1004.10.1016/j.imbio.2010.01.004
    1. Ardeshir A, Narayan NR, Méndez-Lagares G, Lu D, Rauch M, Huang Y, et al. Breast-fed and bottle-fed infant rhesus macaques develop distinct gut microbiotas and immune systems. Sci Transl Med (2014) 6(252):252ra120.10.1126/scitranslmed.3008791
    1. World Health Organization. Exclusive Breastfeeding. (2018) Available from:
    1. Koenig JE, Spor A, Scalfone N, Fricker AD, Stombaugh J, Knight R, et al. Succession of microbial consortia in the developing infant gut microbiome. Proc Natl Acad Sci U S A (2011) 108(Suppl 1):4578–85.10.1073/pnas.1000081107
    1. Brandtzaeg P. Mucosal immunity: integration between mother and the breast-fed infant. Vaccine (2003) 21(24):3382–8.10.1016/S0264-410X(03)00338-4
    1. Cox LM, Yamanishi S, Sohn J, Alekseyenko AV, Leung JM, Cho I, et al. Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences. Cell (2014) 158(4):705–21.10.1016/j.cell.2014.05.052
    1. Olszak T, An D, Zeissig S, Vera MP, Richter J, Franke A, et al. Microbial exposure during early life has persistent effects on natural killer T cell function. Science (2012) 336(6080):489–93.10.1126/science.1219328
    1. Cahenzli J, Koller Y, Wyss M, Geuking MB, McCoy KD. Intestinal microbial diversity during early-life colonization shapes long-term IgE levels. Cell Host Microbe (2013) 14(5):559–70.10.1016/j.chom.2013.10.004
    1. Arrieta MC, Stiemsma LT, Dimitriu PA, Thorson L, Russell S, Yurist-Doutsch S, et al. Early infancy microbial and metabolic alterations affect risk of childhood asthma. Sci Transl Med (2015) 7(307):307ra152.10.1126/scitranslmed.aab2271
    1. Fujimura KE, Sitarik AR, Havstad S, Lin DL, Levan S, Fadrosh D, et al. Neonatal gut microbiota associates with childhood multisensitized atopy and T cell differentiation. Nat Med (2016) 22(10):1187–91.10.1038/nm.4176
    1. Bäckhed 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):690–703.10.1016/j.chom.2015.04.004
    1. Ding T, Schloss PD. Dynamics and associations of microbial community types across the human body. Nature (2014) 509(7500):357–60.10.1038/nature13178
    1. Townsend CL, Peckham CS, Thorne C. Breastfeeding and transmission of viruses other than HIV-1. Adv Exp Med Biol (2012) 743:27–38.10.1007/978-1-4614-2251-8_2
    1. Reyes A, Blanton LV, Cao S, Zhao G, Manary M, Trehan I, et al. Gut DNA viromes of Malawian twins discordant for severe acute malnutrition. Proc Natl Acad Sci U S A (2015) 112(38):11941–6.10.1073/pnas.1514285112
    1. Breitbart M, Haynes M, Kelley S, Angly F, Edwards RA, Felts B, et al. Viral diversity and dynamics in an infant gut. Res Microbiol (2008) 159(5):367–73.10.1016/j.resmic.2008.04.006
    1. Duranti S, Lugli GA, Mancabelli L, Armanini F, Turroni F, James K, et al. Maternal inheritance of bifidobacterial communities and bifidophages in infants through vertical transmission. Microbiome (2017) 5(1):66.10.1186/s40168-017-0282-6
    1. Lim ES, Zhou Y, Zhao G, Bauer IK, Droit L, Ndao IM, et al. Early life dynamics of the human gut virome and bacterial microbiome in infants. Nat Med (2015) 21(10):1228–34.10.1038/nm.3950
    1. Ward RE, Ninonuevo M, Mills DA, Lebrilla CB, German JB. In vitro fermentation of breast milk oligosaccharides by Bifidobacterium infantis and Lactobacillus gasseri. Appl Environ Microbiol (2006) 72(6):4497–9.10.1128/AEM.02515-05
    1. Bode L. Human milk oligosaccharides: every baby needs a sugar mama. Glycobiology (2012) 22(9):1147–62.10.1093/glycob/cws074
    1. Ruiz-Palacios GM, Cervantes LE, Ramos P, Chavez-Munguia B, Newburg DS. Campylobacter jejuni binds intestinal H(O) antigen (Fuc alpha 1, 2Gal beta 1, 4GlcNAc), and fucosyloligosaccharides of human milk inhibit its binding and infection. J Biol Chem (2003) 278(16):14112–20.10.1074/jbc.M207744200
    1. Newburg DS, Ruiz-Palacios GM, Morrow AL. Human milk glycans protect infants against enteric pathogens. Annu Rev Nutr (2005) 25:37–58.10.1146/annurev.nutr.25.050304.092553
    1. Kuntz S, Kunz C, Rudloff S. Oligosaccharides from human milk induce growth arrest via G2/M by influencing growth-related cell cycle genes in intestinal epithelial cells. Br J Nutr (2009) 101(9):1306–15.10.1017/S0007114508079622
    1. Eiwegger T, Stahl B, Haidl P, Schmitt J, Boehm G, Dehlink E, et al. Prebiotic oligosaccharides: in vitro evidence for gastrointestinal epithelial transfer and immunomodulatory properties. Pediatr Allergy Immunol (2010) 21(8):1179–88.10.1111/j.1399-3038.2010.01062.x
    1. Thurl S, Munzert M, Henker J, Boehm G, Muller-Werner B, Jelinek J, et al. Variation of human milk oligosaccharides in relation to milk groups and lactational periods. Br J Nutr (2010) 104(9):1261–71.10.1017/S0007114510002072
    1. Chaturvedi P, Warren CD, Altaye M, Morrow AL, Ruiz-Palacios G, Pickering LK, et al. Fucosylated human milk oligosaccharides vary between individuals and over the course of lactation. Glycobiology (2001) 11(5):365–72.10.1093/glycob/11.5.365
    1. Zivkovic AM, German JB, Lebrilla CB, Mills DA. Human milk glycobiome and its impact on the infant gastrointestinal microbiota. Proc Natl Acad Sci U S A (2011) 108(Suppl 1):4653–8.10.1073/pnas.1000083107
    1. Kobata A. Structures and application of oligosaccharides in human milk. Proc Jpn Acad Ser B Phys Biol Sci (2010) 86(7):731–47.10.2183/pjab.86.731
    1. Lewis ZT, Totten SM, Smilowitz JT, Popovic M, Parker E, Lemay DG, et al. Maternal fucosyltransferase 2 status affects the gut bifidobacterial communities of breastfed infants. Microbiome (2015) 3:13.10.1186/s40168-015-0071-z
    1. Panigrahi P, Parida S, Nanda NC, Satpathy R, Pradhan L, Chandel DS, et al. A randomized synbiotic trial to prevent sepsis among infants in rural India. Nature (2017) 548(7668):407–12.10.1038/nature23480
    1. 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):2–8.10.1203/01.pdr.0000250274.68571.18
    1. Morrow AL, Ruiz-Palacios GM, Altaye M, Jiang X, Guerrero ML, Meinzen-Derr JK, et al. Human milk oligosaccharide blood group epitopes and innate immune protection against Campylobacter and calicivirus diarrhea in breastfed infants. Adv Exp Med Biol (2004) 554:443–6.10.1007/978-1-4757-4242-8_61
    1. Morrow AL, Ruiz-Palacios GM, Jiang X, Newburg DS. Human-milk glycans that inhibit pathogen binding protect breast-feeding infants against infectious diarrhea. J Nutr (2005) 135(5):1304–7.10.1093/jn/135.5.1304
    1. Laucirica DR, Triantis V, Schoemaker R, Estes MK, Ramani S. Milk oligosaccharides inhibit human rotavirus infectivity in MA104 cells. J Nutr (2017) 147:1709–14.10.3945/jn.116.246090
    1. Nordgren J, Sharma S, Bucardo F, Nasir W, Gunaydin G, Ouermi D, et al. Both Lewis and secretor status mediate susceptibility to rotavirus infections in a rotavirus genotype-dependent manner. Clin Infect Dis (2014) 59(11):1567–73.10.1093/cid/ciu633
    1. Payne DC, Currier RL, Staat MA, Sahni LC, Selvarangan R, Halasa NB, et al. Epidemiologic association between FUT2 secretor status and severe rotavirus gastroenteritis in children in the United States. JAMA Pediatr (2015) 169(11):1040–5.10.1001/jamapediatrics.2015.2002
    1. Morrow AL, Ruiz-Palacios GM, Altaye M, Jiang X, Guerrero ML, Meinzen-Derr JK, et al. Human milk oligosaccharides are associated with protection against diarrhea in breast-fed infants. J Pediatr (2004) 145(3):297–303.10.1016/j.jpeds.2004.04.054
    1. Bode L, Kuhn L, Kim HY, Hsiao L, Nissan C, Sinkala M, et al. Human milk oligosaccharide concentration and risk of postnatal transmission of HIV through breastfeeding. Am J Clin Nutr (2012) 96(4):831–9.10.3945/ajcn.112.039503
    1. Barthelson R, Mobasseri A, Zopf D, Simon P. Adherence of Streptococcus pneumoniae to respiratory epithelial cells is inhibited by sialylated oligosaccharides. Infect Immun (1998) 66(4):1439–44.
    1. Bode L. The functional biology of human milk oligosaccharides. Early Hum Dev (2015) 91(11):619–22.10.1016/j.earlhumdev.2015.09.001
    1. Andersson B, Porras O, Hanson LA, Lagergard T, Svanborg-Eden C. Inhibition of attachment of Streptococcus pneumoniae and Haemophilus influenzae by human milk and receptor oligosaccharides. J Infect Dis (1986) 153(2):232–7.10.1093/infdis/153.2.232
    1. Cravioto A, Tello A, Villafan H, Ruiz J, del Vedovo S, Neeser JR. Inhibition of localized adhesion of enteropathogenic Escherichia coli to HEp-2 cells by immunoglobulin and oligosaccharide fractions of human colostrum and breast milk. J Infect Dis (1991) 163(6):1247–55.10.1093/infdis/163.6.1247
    1. 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):33–46.10.1136/gutjnl-2014-307544
    1. Idanpaan-Heikkila I, Simon PM, Zopf D, Vullo T, Cahill P, Sokol K, et al. Oligosaccharides interfere with the establishment and progression of experimental pneumococcal pneumonia. J Infect Dis (1997) 176(3):704–12.10.1086/514094
    1. Andreas NJ, Al-Khalidi A, Jaiteh M, Clarke E, Hyde MJ, Modi N, et al. Role of human milk oligosaccharides in Group B Streptococcus colonisation. Clin Transl Immunology (2016) 5(8):e99.10.1038/cti.2016.43
    1. Ackerman DL, Doster RS, Weitkamp JH, Aronoff DM, Gaddy JA, Townsend SD. Human milk oligosaccharides exhibit antimicrobial and antibiofilm properties against Group B Streptococcus. ACS Infect Dis (2017) 3(8):595–605.10.1021/acsinfecdis.7b00064
    1. Lin AE, Autran CA, Szyszka A, Escajadillo T, Huang M, Godula K, et al. Human milk oligosaccharides inhibit growth of group B Streptococcus. J Biol Chem (2017) 292(27):11243–9.10.1074/jbc.M117.789974
    1. Koromyslova A, Tripathi S, Morozov V, Schroten H, Hansman GS. Human norovirus inhibition by a human milk oligosaccharide. Virology (2017) 508:81–9.10.1016/j.virol.2017.04.032
    1. Schijf MA, Kruijsen D, Bastiaans J, Coenjaerts FE, Garssen J, van Bleek GM, et al. Specific dietary oligosaccharides increase Th1 responses in a mouse respiratory syncytial virus infection model. J Virol (2012) 86(21):11472–82.10.1128/JVI.06708-11
    1. van Bergenhenegouwen J, Kraneveld AD, Rutten L, Kettelarij N, Garssen J, Vos AP. Extracellular vesicles modulate host-microbe responses by altering TLR2 activity and phagocytosis. PLoS One (2014) 9(2):e89121.10.1371/journal.pone.0089121
    1. Zempleni J, Aguilar-Lozano A, Sadri M, Sukreet S, Manca S, Wu D, et al. Biological activities of extracellular vesicles and their cargos from bovine and human milk in humans and implications for infants. J Nutr (2017) 147(1):3–10.10.3945/jn.116.238949
    1. Admyre C, Johansson SM, Qazi KR, Filen JJ, Lahesmaa R, Norman M, et al. Exosomes with immune modulatory features are present in human breast milk. J Immunol (2007) 179(3):1969–78.10.4049/jimmunol.179.3.1969
    1. Zonneveld MI, Brisson AR, van Herwijnen MJ, Tan S, van de Lest CH, Redegeld FA, et al. Recovery of extracellular vesicles from human breast milk is influenced by sample collection and vesicle isolation procedures. J Extracell Vesicles (2014) 3.10.3402/jev.v3.24215
    1. Lasser C, Alikhani VS, Ekstrom K, Eldh M, Paredes PT, Bossios A, et al. Human saliva, plasma and breast milk exosomes contain RNA: uptake by macrophages. J Transl Med (2011) 9:9.10.1186/1479-5876-9-9
    1. Karlsson O, Rodosthenous RS, Jara C, Brennan KJ, Wright RO, Baccarelli AA, et al. Detection of long non-coding RNAs in human breastmilk extracellular vesicles: implications for early child development. Epigenetics (2016) 11(10):721–29.10.1080/15592294.2016.1216285
    1. Yang M, Song D, Cao X, Wu R, Liu B, Ye W, et al. Comparative proteomic analysis of milk-derived exosomes in human and bovine colostrum and mature milk samples by iTRAQ-coupled LC-MS/MS. Food Res Int (2017) 92:17–25.10.1016/j.foodres.2016.11.041
    1. Kosaka N, Izumi H, Sekine K, Ochiya T. MicroRNA as a new immune-regulatory agent in breast milk. Silence (2010) 1(1):7.10.1186/1758-907X-1-7
    1. 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(1):118–23.10.7150/ijbs.8.118
    1. Henrick BM, Yao XD, Nasser L, Roozrogousheh A, Rosenthal KL. Breastfeeding behaviors and the innate immune system of human milk: working together to protect infants against inflammation, HIV-1, and other infections. Front Immunol (2017) 8:1631.10.3389/fimmu.2017.01631
    1. 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):3412–23.10.1074/mcp.M116.060426
    1. Samuel M, Chisanga D, Liem M, Keerthikumar S, Anand S, Ang CS, et al. Bovine milk-derived exosomes from colostrum are enriched with proteins implicated in immune response and growth. Sci Rep (2017) 7(1):5933.10.1038/s41598-017-06288-8
    1. Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol (2007) 9(6):654–9.10.1038/ncb1596
    1. Hata T, Murakami K, Nakatani H, Yamamoto Y, Matsuda T, Aoki N. Isolation of bovine milk-derived microvesicles carrying mRNAs and microRNAs. Biochem Biophys Res Commun (2010) 396(2):528–33.10.1016/j.bbrc.2010.04.135
    1. Title AC, Denzler R, Stoffel M. Uptake and function studies of maternal milk-derived microRNAs. J Biol Chem (2015) 290(39):23680–91.10.1074/jbc.M115.676734
    1. Naslund TI, Paquin-Proulx D, Paredes PT, Vallhov H, Sandberg JK, Gabrielsson S. Exosomes from breast milk inhibit HIV-1 infection of dendritic cells and subsequent viral transfer to CD4+ T cells. AIDS (2014) 28(2):171–80.10.1097/QAD.0000000000000159
    1. Liao Y, Du X, Li J, Lonnerdal B. Human milk exosomes and their microRNAs survive digestion in vitro and are taken up by human intestinal cells. Mol Nutr Food Res (2017) 61(11).10.1002/mnfr.201700082
    1. Chen T, Xie MY, Sun JJ, Ye RS, Cheng X, Sun RP, et al. Porcine milk-derived exosomes promote proliferation of intestinal epithelial cells. Sci Rep (2016) 6:33862.10.1038/srep33862
    1. Hock A, Miyake H, Li B, Lee C, Ermini L, Koike Y, et al. Breast milk-derived exosomes promote intestinal epithelial cell growth. J Pediatr Surg (2017) 52(5):755–9.10.1016/j.jpedsurg.2017.01.032
    1. Zhou F, Paz HA, Sadri M, Fernando SC, Zempleni J. A diet defined by its content of bovine milk exosomes alters the composition of the intestinal microbiome in C57BL/6 mice. FASEB J (2017) 31(1 Suppl):965.24.
    1. Simpson MR, Brede G, Johansen J, Johnsen R, Storro O, Saetrom P, et al. Human breast milk miRNA, maternal probiotic supplementation and atopic dermatitis in offspring. PLoS One (2015) 10(12):e0143496.10.1371/journal.pone.0143496
    1. H Rashed M, Bayraktar E, K Helal G, Abd-Ellah MF, Amero P, Chavez-Reyes A, et al. Exosomes: from garbage bins to promising therapeutic targets. Int J Mol Sci (2017) 18(3).10.3390/ijms18030538
    1. Consortium E-T, Van Deun J, Mestdagh P, Agostinis P, Akay O, Anand S, et al. EV-TRACK: transparent reporting and centralizing knowledge in extracellular vesicle research. Nat Methods (2017) 14(3):228–32.10.1038/nmeth.4185

Source: PubMed

赞助者和合作者

医疗条件

药物干预

3
订阅