The Prebiotic and Probiotic Properties of Human Milk: Implications for Infant Immune Development and Pediatric Asthma

Shirin Moossavi, Kozeta Miliku, Shadi Sepehri, Ehsan Khafipour, Meghan B Azad, Shirin Moossavi, Kozeta Miliku, Shadi Sepehri, Ehsan Khafipour, Meghan B Azad

Abstract

The incidence of pediatric asthma has increased substantially in recent decades, reaching a worldwide prevalence of 14%. This rapid increase may be attributed to the loss of "Old Friend" microbes from the human microbiota resulting in a less diverse and "dysbiotic" gut microbiota, which fails to optimally stimulate immune development during infancy. This hypothesis is supported by observations that the gut microbiota is different in infants who develop asthma later in life compared to those who remain healthy. Thus, early life exposures that influence gut microbiota play a crucial role in asthma development. Breastfeeding is one such exposure; it is generally considered protective against pediatric asthma, although conflicting results have been reported, potentially due to variations in milk composition between individuals and across populations. Human milk oligosaccharides (HMOs) and milk microbiota are two major milk components that influence the infant gut microbiota and hence, development of the immune system. Among their many immunomodulatory functions, HMOs exert a selective pressure within the infant gut microbial niche, preferentially promoting the proliferation of specific bacteria including Bifidobacteria. Milk is also a source of viable bacteria originating from the maternal gut and infant oral cavity. As such, breastmilk has prebiotic and probiotic properties that can modulate two of the main forces controlling the gut microbial community assembly, i.e., dispersal and selection. Here, we review the latest evidence, mechanisms and hypotheses for the synergistic and/or additive effects of milk microbiota and HMOs in protecting against pediatric asthma.

Keywords: asthma; human milk; human milk oligosaccharides; immune development; microbiota; pediatrics; prebiotic; probiotic.

Figures

Figure 1
Figure 1
Hypothesized pathways of association between breastfeeding and lung health. Breastfeeding influences infant gut microbiota development and stability during the critical developmental period in early life via two of its main components: human milk oligosaccharides (HMOs) and milk microbiota. HMOs exert a selective pressure within the infant gut microbial niche, preferentially promoting the proliferation of specific bacteria including Bifidobacteria. Milk is also a source of viable bacteria originating from the maternal gut and infant oral cavity. HMO composition is influenced by maternal genetics, geography, and season while microbiota is affected by maternal weight status, mode of breastfeeding and infant sex (Table 1). Variations in HMOs and milk microbiota could modulate the effect of breastfeeding on the infant gut microbiota, which in turn shapes the infant immune system and could ultimately influence lung health and asthma development.

References

    1. Binns C, Lee M, Low WY. The long-term public health benefits of breastfeeding. Asia Pac J Public Health (2016) 28:7–14. 10.1177/1010539515624964
    1. Dogaru CM, Nyffenegger D, Pescatore AM, Spycher BD, Kuehni CE. Breastfeeding and childhood asthma: systematic review and meta-analysis. Am J Epidemiol. (2014) 179:1153–67. 10.1093/aje/kwu072
    1. Ek WE, Karlsson T, Hernándes CA, Rask-Andersen M, Johansson Å. Breast-feeding and risk of asthma, hay fever, and eczema. J Allergy Clin Immunol. (2018) 141:1157–9.e9. 10.1016/j.jaci.2017.10.022
    1. Oddy WH. Breastfeeding, Childhood Asthma, and Allergic Disease. Ann Nutr Metab. (2017) 70 (Suppl. 2):26–36. 10.1159/000457920
    1. Dong GH, Qian ZM, Liu MM, Wang D, Ren WH, Bawa S, et al. . Breastfeeding as a modifier of the respiratory effects of air pollution in children. Epidemiology (2013) 24:387–94. 10.1097/EDE.0b013e3182877eb8
    1. Montgomery SM, Ehlin A, Sacker A. Breast feeding and resilience against psychosocial stress. Arch Dis Child. (2006) 91:990–4. 10.1136/adc.2006.096826
    1. Dogaru CM, Narayanan M, Spycher BD, Pescatore AM, Owers-Bradley J, Beardsmore CS, et al. . Breastfeeding, lung volumes and alveolar size at school-age. BMJ Open Respir Res. (2015) 2:e000081. 10.1136/bmjresp-2015-000081
    1. Waidyatillake NT, Allen KJ, Lodge CJ, Dharmage SC, Abramson MJ, Simpson JA, et al. . The impact of breastfeeding on lung development and function: a systematic review. Expert Rev Clin Immunol. (2013) 9:1253–65. 10.1586/1744666X.2013.851005
    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) 49:1602019. 10.1183/13993003.02019-2016
    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. 10.1016/j.jpeds.2017.07.012
    1. 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) 5:571–3. 10.3945/an.114.006643
    1. Abrahamsson TR, Jakobsson HE, Andersson AF, Bjorksten B, Engstrand L, Jenmalm MC. Low gut microbiota diversity in early infancy precedes asthma at school age. Clin Exp Allergy (2014) 44:842–50. 10.1111/cea.12253
    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) 7:307ra152. 10.1126/scitranslmed.aab2271
    1. Subbarao P, Mandhane PJ, Sears MR. Asthma: epidemiology, etiology and risk factors. CMAJ (2009) 181:E181–90. 10.1503/cmaj.080612
    1. Blaser MJ, Falkow S. What are the consequences of the disappearing human microbiota? Nat Rev Microbiol. (2009) 7:887–94. 10.1038/nrmicro2245
    1. Rook GA. 99th Dahlem conference on infection, inflammation and chronic inflammatory disorders: darwinian medicine and the ‘hygiene’ or ‘old friends’ hypothesis. Clin Exp Immunol. (2010) 160:70–9. 10.1111/j.1365-2249.2010.04133.x
    1. Ruokolainen L, Paalanen L, Karkman A, Laatikainen T, von Hertzen L, Vlasoff T, et al. . Significant disparities in allergy prevalence and microbiota between the young people in Finnish and Russian Karelia. Clin Exp Allergy (2017) 47:665–74. 10.1111/cea.12895
    1. Azad MB, Kozyrskyj AL. Perinatal programming of asthma: the role of gut microbiota. Clin Dev Immunol. (2012) 2012:932072. 10.1155/2012/932072
    1. 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) 21:400–5. 10.1016/j.siny.2016.05.003
    1. Andreas NJ, Kampmann B, Mehring Le-Doare K. Human breast milk: a review on its composition and bioactivity. Early Hum Dev. (2015) 91:629–35. 10.1016/j.earlhumdev.2015.08.013
    1. Ardeshir A, Narayan NR, Mendez-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) 6:252ra120. 10.1126/scitranslmed.3008791
    1. Munblit D, Peroni DG, Boix-Amoros A, Hsu PS, Van't Land B, Gay MCL, et al. . Human milk and allergic diseases: an unsolved puzzle. Nutrients (2017) 9:E894. 10.3390/nu9080894
    1. Kunz C, Rudloff S, Baier W, Klein N, Strobel S. Oligosaccharides in human milk: structural, functional, and metabolic aspects. Annu Rev Nutr. (2000) 20:699–722. 10.1146/annurev.nutr.20.1.699
    1. Smilowitz JT, Lebrilla CB, Mills DA, German JB, Freeman SL. Breast milk oligosaccharides: structure-function relationships in the neonate. Annu Rev Nutr. (2014) 34:143–69. 10.1146/annurev-nutr-071813-105721
    1. McGuire MK, Meehan CL, McGuire MA, Williams JE, Foster J, Sellen DW, et al. . What's normal? Oligosaccharide concentrations and profiles in milk produced by healthy women vary geographically. Am J Clin Nutr. (2017) 105:1086–100. 10.3945/ajcn.116.139980
    1. Miliku K, Robertson B, Sharma AK, Subbarao P, Becker AB, Mandhane PJ, et al. . Human milk oligosaccharide profiles and food sensitization among infants in the CHILD Study. Allergy (2018) [Epub ahead of print]. 10.1111/all.13476
    1. Davis JC, Lewis ZT, Krishnan S, Bernstein RM, Moore SE, Prentice AM, et al. . Growth and morbidity of gambian infants are influenced by maternal milk oligosaccharides and infant gut microbiota. Sci Rep. (2017) 7:40466. 10.1038/srep40466
    1. Chaturvedi P, Warren CD, Altaye M, Morrow AL, Ruiz-Palacios GP, Newburg LK. D. S. Fucosylated human milk oligosaccharides vary between individuals and over the course of lactation. Glycobiology (2001) 11:365–72. 10.1093/glycob/11.5.365
    1. Sprenger N, Odenwald H, Kukkonen AK, Kuitunen M, Savilahti E, Kunz C. FUT2-dependent breast milk oligosaccharides and allergy at 2 and 5 years of age in infants with high hereditary allergy risk. Eur J Nutr. (2017) 56:1293–301. 10.1007/s00394-016-1180-6
    1. Marcobal A, Sonnenburg JL. Human milk oligosaccharide consumption by intestinal microbiota. Clin Microbiol Infect. (2012) 18(Suppl. 4):12–5. 10.1111/j.1469-0691.2012.03863.x
    1. Bode L. The functional biology of human milk oligosaccharides. Early Hum Dev. (2015) 91:619–22. 10.1016/j.earlhumdev.2015.09.001
    1. Kuntz S, Rudloff S, Kunz C. Oligosaccharides from human milk influence growth-related characteristics of intestinally transformed and non-transformed intestinal cells. Br J Nutr. (2008) 99:462–71. 10.1017/S0007114507824068
    1. Seppo AE, Autran CA, Bode L, Jarvinen KM. Human milk oligosaccharides and development of cow's milk allergy in infants. J Allergy Clin Immunol. (2017) 139:708–11.e5. 10.1016/j.jaci.2016.08.031
    1. Moossavi S, Khafipour E, Sepehri S, Robertson B, Bode L, Becker AB, et al. Maternal and early life factors influencing the human milk microbiota in the child cohort. In: Poster Session Presented at: Canadian Society of Microbiololists. Waterloo, ON: (2017).
    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. Boehm G, Stahl B. Oligosaccharides from milk. J Nutr. (2007) 137(3 Suppl. 2):847s−9s. 10.1093/jn/137.3.847S
    1. Xu G, Davis JC, Goonatilleke E, Smilowitz JT, German JB, Lebrilla CB. Absolute quantitation of human milk oligosaccharides reveals phenotypic variations during lactation. J Nutr. (2017) 147:117–24. 10.3945/jn.116.238279
    1. Bode L. Human milk oligosaccharides: every baby needs a sugar mama. Glycobiology (2012) 22:1147–62. 10.1093/glycob/cws074
    1. Comstock SS, Wang M, Hester SN, Li M, Donovan SM. Select human milk oligosaccharides directly modulate peripheral blood mononuclear cells isolated from 10-d-old pigs. Br J Nutr. (2014) 111:819–28. 10.1017/S0007114513003267
    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) 86:11472–82. 10.1128/JVI.06708-11
    1. Pandey RP, Kim DH, Woo J, Song J, Jang SH, Kim JB, et al. . Broad-spectrum neutralization of avian influenza viruses by sialylated human milk oligosaccharides: in vivo assessment of 3'-sialyllactose against H9N2 in chickens. Sci Rep. (2018) 8:2563. 10.1038/s41598-018-20955-4
    1. Vos AP, van Esch BC, Stahl B, M'Rabet L, Folkerts G, Nijkamp FP, et al. . Dietary supplementation with specific oligosaccharide mixtures decreases parameters of allergic asthma in mice. Int Immunopharmacol. (2007) 7:1582–7. 10.1016/j.intimp.2007.07.024
    1. Arslanoglu S, Moro GE, Boehm G, Wienz F, Stahl B, Bertino E. Early neutral prebiotic oligosaccharide supplementation reduces the incidence of some allergic manifestations in the first 5 years of life. J Biol Regulators Homeost Agents (2012) 26(3 Suppl.):49–59. 10.1088/2058-7058/26/08/11
    1. Castillo-Courtade L, Han S, Lee S, Mian FM, Buck R, Forsythe P. Attenuation of food allergy symptoms following treatment with human milk oligosaccharides in a mouse model. Allergy (2015) 70:1091–102. 10.1111/all.12650
    1. Osborn DA, Sinn JK. Prebiotics in infants for prevention of allergy. Cochrane Database Syst Rev. (2013) CD006474. 10.1002/14651858.CD006474
    1. Fitzstevens JL, Smith KC, Hagadorn JI, Caimano MJ, Matson AP, Brownell EA. Systematic review of the human milk microbiota. Nutr Clin Pract. (2016) 32:354–64. 10.1177/0884533616670150
    1. Heikkila MP, Saris PEJ. Inhibition of Staphylococcus aureus by the commensal bacteria of human milk. J Appl Microbiol. (2003) 95:471–8. 10.1046/j.1365-2672.2003.02002.x
    1. McGuire MK, McGuire MA. Got bacteria? The astounding, yet not-so-surprising, microbiome of human milk. Curr Opin Biotechnol. (2017) 44:63–8. 10.1016/j.copbio.2016.11.013
    1. Collado MC, Laitinen K, Salminen S, Isolauri E. Maternal weight and excessive weight gain during pregnancy modify the immunomodulatory potential of breast milk. Pediatr Res. (2012) 72:77–85. 10.1038/pr.2012.42
    1. West PA, Hewitt JH, Murphy OM. The influence of methods of collection and storage on the bacteriology of human milk. J Appl Bacteriol. (1979) 46:269–77.
    1. 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) 69:1–10. 10.1016/j.phrs.2012.09.001
    1. Azad MB, Coneys JG, Kozyrskyj AL, Field CJ, Ramsey CD, Becker AB, et al. . Probiotic supplementation during pregnancy or infancy for the prevention of asthma and wheeze: systematic review and meta-analysis. BMJ (2013) 347:f6471. 10.1136/bmj.f6471
    1. Laforest-Lapointe I, Arrieta MC. Patterns of early-life gut microbial colonization during human immune development: an ecological perspective. Front Immunol. (2017) 8:788. 10.3389/fimmu.2017.00788
    1. Asnicar F, Manara S, Zolfo M, Truong DT, Scholz M, Armanini F, et al. . Studying vertical microbiome transmission from mothers to infants by strain-level metagenomic profiling. mSystems (2017) 2:e00164–16. 10.1128/mSystems.00164-16
    1. Wang M, Li M, Wu S, Lebrilla CB, Chapkin RS, Ivanov I, et al. . Fecal microbiota composition of breast-fed infants is correlated with human milk oligosaccharides consumed. J Pediatr Gastroenterol Nutr. (2015) 60:825–33. 10.1097/MPG.0000000000000752
    1. Ruiz-Moyano S, Totten SM, Garrido DA, Smilowitz JT, German JB, Lebrilla CB, et al. . Variation in consumption of human milk oligosaccharides by infant gut-associated strains of bifidobacterium breve. Appl Environ Microbiol. (2013) 79:6040–9. 10.1128/AEM.01843-13
    1. Davis JC, Totten SM, Huang JO, Nagshbandi S, Kirmiz N, Garrido DA, et al. . Identification of oligosaccharides in feces of breast-fed infants and their correlation with the gut microbial community. Mol Cell Proteomics (2016) 15:2987–3002.
    1. Angeloni S, Ridet JL, Kusy N, Gao H, Crevoisier F, Guinchard S, et al. . Glycoprofiling with micro-arrays of glycoconjugates and lectins. Glycobiology (2005) 15:31–41. 10.1093/glycob/cwh143
    1. Fukami T. Historical contingency in community assembly: integrating niches, species pools, and priority effects. Annu Rev Ecol Evol Syst. (2015) 46:1–23. 10.1146/annurev-ecolsys-110411-160340
    1. Obadia B, Guvener ZT, Zhang V, Ceja-Navarro JA, Brodie EL, Ja WW, et al. . Probabilistic Invasion Underlies Natural Gut Microbiome Stability. Curr Biol. (2017) 27:1999–2006 e8. 10.1016/j.cub.2017.05.034
    1. Li M, Wang M, Donovan SM. Early development of the gut microbiome and immune-mediated childhood disorders. Semin Reprod Med. (2014) 32:74–86. 10.1055/s-0033-1361825
    1. Kaplan JL, Shi HN, Walker WA. The role of microbes in developmental immunologic programming. Pediatr Res. (2011) 69:465–72. 10.1203/PDR.0b013e318217638a
    1. Wang M, Monaco MH, Donovan SM. Impact of early gut microbiota on immune and metabolic development and function. Semin Fetal Neonatal Med. (2016) 21:380–7. 10.1016/j.siny.2016.04.004
    1. Tanaka M, Nakayama J. Development of the gut microbiota in infancy and its impact on health in later life. Allergol Int. (2017) 66:515–22. 10.1016/j.alit.2017.07.010
    1. Huffnagle GB. The microbiota and allergies/asthma. PLoS Pathog. (2010) 6:e1000549. 10.1371/journal.ppat.1000549
    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. Gollwitzer ES, Marsland BJ. Impact of early-life exposures on immune maturation and susceptibility to disease. Trends Immunol. (2015) 36:684–96. 10.1016/j.it.2015.09.009
    1. Lundell AC, Bjornsson V, Ljung A, Ceder M, Johansen S, Lindhagen G, et al. . Infant B cell memory differentiation and early gut bacterial colonization. J Immunol. (2012) 188:4315–22. 10.4049/jimmunol.1103223
    1. Fujimura KE, Lynch SV. Microbiota in allergy and asthma and the emerging relationship with the gut microbiome. Cell Host Microbe. (2015) 17:592–602. 10.1016/j.chom.2015.04.007
    1. Gensollen T, Blumberg RS. Correlation between early-life regulation of the immune system by microbiota and allergy development. J Allergy Clin Immunol. (2017) 139:1084–91. 10.1016/j.jaci.2017.02.011
    1. Penders J, Thijs C, van den Brandt PA, Kummeling I, Snijders B, Stelma F, et al. . Gut microbiota composition and development of atopic manifestations in infancy: the KOALA Birth Cohort Study. Gut (2007) 56:661–7. 10.1136/gut.2006.100164
    1. Vael C, Vanheirstraeten L, Desager KN, Goossens H. Denaturing gradient gel electrophoresis of neonatal intestinal microbiota in relation to the development of asthma. BMC Microbiol. (2011) 11:68. 10.1186/1471-2180-11-68
    1. Stiemsma LT, Arrieta MC, Dimitriu PA, Cheng J, Thorson L, Lefebvre DL, et al. . Shifts in Lachnospira and Clostridium sp. in the 3-month stool microbiome are associated with preschool age asthma. Clin Sci. (2016) 130:2199–207. 10.1042/CS20160349
    1. Kalliomaki M, Kirjavainen P, Eerola E, Kero P, Salminen S, Isolauri E. Distinct patterns of neonatal gut microflora in infants in whom atopy was and was not developing. J Allergy Clin Immunol. (2001) 107:129–34. 10.1067/mai.2001.111237
    1. Stiemsma LT, Turvey SE. Asthma and the microbiome: defining the critical window in early life. Allergy Asthma Clin Immunol. (2017) 13:3. 10.1186/s13223-016-0173-6

Source: PubMed

Спонсоры и соавторы

Заболевания

Медикаментозные вмешательства

Подписаться