母乳主要活性成分对婴儿肠道及免疫功能影响的研究进展

doi:10.11852/zgetbjzz2023-0907

摘要/Abstract

摘要： 肠道微生物组在维持一生健康方面发挥着重要作用。婴儿时期是肠道菌群建立的关键时期,会受到多种因素影响,包括分娩方式、抗生素和喂养方式等。母乳中含有多种生物活性因子,如母乳低聚糖、分泌型免疫球蛋白、母乳微生物群等,对婴儿微生物群的建立和稳定发挥了重要作用。本文将综合阐述上述母乳生物活性因子影响婴儿微生物群定植和发展的最新研究进展,及上述物质如何通过肠道细菌影响免疫功能。

关键词: 母乳, 婴儿, 生物活性物质, 肠道菌群, 免疫

Abstract: Gut microbiome plays an important role in maintaining lifelong health. Infancy is a critical period for the establishment of gut microbiota, which is influenced by many factors, including delivery methods, antibiotics, and feeding mode. Human milk contains a variety of bioactive factors, such as human milk oligosaccharide, secretory immunoglobulin, and human milk microbiota, which play important roles in the establishment and stability of newborn microbiota. This article presents the latest research progress on the effects of the aforementioned bioactive factors in breast milk on the colonization and development of infant microbiota, and explains how these substances affect immune function through intestinal bacteria.

Key words: breast milk, infant, bioactive substances, gut microbiota, immunity

中图分类号:

R174.4

吕丽娜, 朱冰泉. 母乳主要活性成分对婴儿肠道及免疫功能影响的研究进展[J]. 中国儿童保健杂志, 2024, 32(4): 424-428.

LYU Lina, ZHU Bingquan. Research progress in the effects of the main active ingredients of breast milk on the intestinal and immune functions of infants[J]. Chinese Journal of Child Health Care, 2024, 32(4): 424-428.

参考文献

[1] Garwolinska D, Namiesnik J, Kot-Wasik A, et al. Chemistry of human breast milk-a comprehensive review of the composition and role of milk metabolites in child development[J]. J Agric Food Chem,2018,66(45):11881-11896.
[2] Nuzzi G, Trambusti I, DI Cicco ME, et al. Breast milk: More than just nutrition![J]. Minerva Pediatr(Torino),2021,73(2):111-114.
[3] Yi DY, Kim SY. Human breast milk composition and function in human health:From nutritional components to microbiome and microRNAs[J]. Nutrients,2021,13(9): 3094.
[4] Brink LR, Mercer KE, Piccolo BD, et al. Neonatal diet alters fecal microbiota and metabolome profiles at different ages in infants fed breast milk or formula[J]. Am J Clin Nutr,2020,111(6):1190-1202.
[5] Forbes JD, Azad MB, Vehling L, et al. Association of exposure to formula in the hospital and subsequent infant feeding practices with gut microbiota and risk of overweight in the first year of life[J]. JAMA Pediatr,2018,172(7):e181161.
[6] Ma J, Li Z, Zhang W, et al. Comparison of gut microbiota in exclusively breast-fed and formula-fed babies: A study of 91 term infants[J]. Sci Rep,2020,10(1):15792.
[7] Ho NT, Li F, Lee-Sarwar KA, et al. Meta-analysis of effects of exclusive breastfeeding on infant gut microbiota across populations[J]. Nat Commun,2018,9(1):4169.
[8] Gopalakrishna KP, Hand TW. Influence of maternal milk on the neonatal intestinal microbiome[J]. Nutrients,2020,12(3):823.
[9] Zhang B, Li LQ, Liu F, et al.Human milk oligosaccharides and infant gut microbiota: Molecular structures, utilization strategies and immune function[J]. Carbohydr Polym,2022,276:118738.
[10] Cheng YJ, Yeung CY.Recent advance in infant nutrition: Human milk oligosaccharides[J]. Pediatr Neonatol,2021,62(4):347-353.
[11] Han SM, Derraik J, Binia A, et al. Maternal and infant factors influencing human milk oligosaccharide composition:Beyond maternal genetics[J]. J Nutr,2021,151(6):1383-1393.
[12] Reverri EJ, Devitt AA, Kajzer JA, et al. Review of the clinical experiences of feeding infants formula containing the human milk oligosaccharide 2'-Fucosyllactose[J]. Nutrients,2018,10(10):1346.
[13] Maessen SE, Derraik J, Binia A, et al. Perspective: Human milk oligosaccharides:Fuel for childhood obesity prevention?[J]. Adv Nutr,2020,11(1):35-40.
[14] Salli K, Hirvonen J, Siitonen J, et al. Selectiveutilization of the human milk oligosaccharides 2'-Fucosyllactose, 3-Fucosyllactose, and difucosyllactose by various probiotic and pathogenic bacteria[J]. J Agric Food Chem,2021,69(1):170-182.
[15] Lawson M, O'Neill IJ, Kujawska M, et al. Breast milk-derived human milk oligosaccharides promote bifidobacterium interactions within a single ecosystem[J]. ISME J,2020,14(2):635-648.
[16] Borewicz K, Gu F, Saccenti E, et al. The association between breastmilk oligosaccharides and faecal microbiota in healthy breastfed infants at two, six, and twelve weeks of age[J]. Sci Rep,2020,10(1):4270.
[17] Natividad JM, Marsaux B, Rodenas C, et al. Humanmilk oligosaccharides and lactose differentially affect infant gut microbiota and intestinal barrier in vitro[J]. Nutrients,2022,14(12):2546.
[18] Nilsen M, Madelen SC, Leena AI, et al. Butyrate levels in the transition from an infant- to an adult-like gut microbiota correlate with bacterial networks associated with eubacterium rectale and ruminococcus gnavus[J].Genes(Basel),2020,11(11):1245.
[19] Wang Y, Zou Y, Wang J, et al. Theprotective effects of 2'-Fucosyllactose against E. Coli O157 infection are mediated by the regulation of gut microbiota and the inhibition of pathogen adhesion[J]. Nutrients,2020,12(5):1284.
[20] Hanisch FG, Hansman GS, Morozov V, et al. Avidity of alpha-fucose on human milk oligosaccharides and blood group-unrelated oligo/polyfucoses is essential for potent norovirus-binding targets[J]. J Biol Chem,2018,293(30):11955-11965.
[21] Natividad JM, Rytz A, Keddani S, et al. Blends of human milk oligosaccharides confer intestinal epithelial barrier protection in vitro[J]. Nutrients,2020,12(10):3047.
[22] Zuurveld M, van Witzenburg NP, Garssen J, et al. Immunomodulation by human milk oligosaccharides:The potential role in prevention of allergic diseases[J]. Front Immunol,2020,11:801.
[23] Liu T, Chen P, Munir M, et al. HMOs modulate immunoregulation and gut microbiota in a β-lactoglobulin-induced allergic mice model[J]. Journal of Functional Foods,2020,70:103993.
[24] Masi AC, Embleton ND, Lamb CA, et al. Human milk oligosaccharide DSLNT and gut microbiome in preterm infants predicts necrotising enterocolitis[J]. Gut,2021,70(12):2273-2282.
[25] Vatanen T, Franzosa EA, Schwager R, et al. The human gut microbiome in early-onset type 1 diabetes from the TEDDY study[J]. Nature,2018,562(7728):589-594.
[26] Rahman T, Sarwar PF, Potter C, et al. Role of human milk oligosaccharide metabolizing bacteria in the development of atopic dermatitis/eczema[J]. Front Pediatr,2023,11:1090048.
[27] Hanson LA. Breastfeeding provides passive and likely long-lasting active immunity[J]. Ann Allergy Asthma Immunol,1998,81(6):523-534, 537.
[28] Rio-Aige K, Azagra-Boronat I, Castell M, et al. Thebreast milk immunoglobulinome[J]. Nutrients,2021,13(6):1810.
[29] Gopalakrishna KP, Macadangdang BR, Rogers MB, et al. Maternal IgA protects against the development of necrotizing enterocolitis in preterm infants[J]. Nat Med,2019,25(7):1110-1115.
[30] Ramanan D, Sefik E, Galvan-Pena S, et al. Animmunologic mode of multigenerational transmission governs a gut treg setpoint[J]. Cell,2020,181(6):1276-1290.
[31] Johnson-Hence CB, Gopalakrishna KP, Bodkin D, et al. Stability and heterogeneity in the anti-microbiota reactivity of human milk-derived Immunoglobulin A[J]. bioRxiv,2023, 220(8):e20220839.
[32] Bridgman SL, Konya T, Azad MB, et al. High fecal IgA is associated with reduced clostridium difficile colonization in infants[J]. Microbes Infect,2016,18(9):543-549.
[33] Rogier EW, Frantz AL, Bruno ME, et al. Secretory antibodies in breast milk promote long-term intestinal homeostasis by regulating the gut microbiota and host gene expression[J]. Proc Natl Acad Sci U S A,2014,111(8):3074-3079.
[34] Donaldson GP, Ladinsky MS, Yu KB, et al. Gut microbiota utilize immunoglobulin a for mucosal colonization[J]. Science,2018,360(6390):795-800.
[35] Nakajima A, Vogelzang A, Maruya M, et al. IgA regulates the composition and metabolic function of gut microbiota by promoting symbiosis between bacteria[J]. J Exp Med,2018,215(8):2019-2034.
[36] Lourenco M, Chaffringeon L, Lamy-Besnier Q, et al. Thespatial heterogeneity of the gut limits predation and fosters coexistence of bacteria and bacteriophages[J]. Cell Host Microbe,2020,28(3):390-401.
[37] Ramanan D, Sefik E, Galvan-Pena S, et al. Animmunologic mode of multigenerational transmission governs a gut treg setpoint[J]. Cell,2020,181(6):1276-1290.
[38] Uchimura Y, Fuhrer T, Li H, et al. Antibodiesset boundaries limiting microbial metabolite penetration and the resultant mammalian host response[J]. Immunity,2018,49(3):545-559.
[39] Gopalakrishna KP, Macadangdang BR, Rogers MB, et al. Maternal IgA protects against the development of necrotizing enterocolitis in preterm infants[J]. Nat Med,2019,25(7):1110-1115.
[40] Luck H, Khan S, Kim JH, et al. Gut-associated IgA(+) immune cells regulate obesity-related insulin resistance[J]. Nat Commun,2019,10(1):3650.
[41] Damaceno QS, Souza JP, Nicoli JR, et al. Evaluation of potential probiotics isolated from human milk and colostrum[J]. Probiotics Antimicrob Proteins,2017,9(4):371-379.
[42] Ojo-Okunola A, Nicol M, du Toit E. Humanbreast milk bacteriome in health and disease[J]. Nutrients,2018,10(11):1643.
[43] Ruiz L, Garcia-Carral C, Rodriguez JM. Unfolding the human milk microbiome landscape in the omics era[J]. Front Microbiol,2019,10:1378.
[44] Lackey KA, Williams JE, Meehan CL, et al. What's normal? Microbiomes in human milk and infant feces are related to each other but vary geographically: The INSPIRE study[J]. Front Nutr,2019,6:45.
[45] Wang S, Wei Y, Liu L, et al. Association between breastmilk microbiota and food allergy in infants[J]. Front Cell Infect Microbiol,2021,11:770913.
[46] Zimmermann P, Curtis N. Breast milk microbiota:A review of the factors that influence composition[J]. J Infect,2020,81(1):17-47.
[47] Banic M, Butorac K, Culjak N, et al. The human milk microbiota produces potential therapeutic biomolecules and shapes the intestinal microbiota of infants[J]. Int J Mol Sci,2022,23(22):14382.
[48] Jiao X, Fu MD, Wang YY, et al. Bifidobacterium and lactobacillus for preventing necrotizing enterocolitis in very-low-birth-weight preterm infants:A systematic review and meta-analysis[J]. World J Pediatr,2020,16(2):135-142.
[49] Mu Q, Tavella VJ, Luo XM. Role of lactobacillus reuteri in human health and diseases[J]. Front Microbiol,2018,9:757.
[50] Nantavisai K, Puttikamonkul S, Chotelersak K, et al. In vitro adhesion property and competition against enteropathogens oflactobacillus strains isolated from Thai infants[J]. Wārasān Songkhlā Nakharin,2018,40(1):69-74.
[51] Gueimonde M, Laitinen K, Salminen S, et al. Breast milk: A source of bifidobacteria for infant gut development and maturation?[J]. Neonatology,2007,92(1):64-66.
[52] Underwood MA, Davis J, Kalanetra KM, et al. Digestion of human milk oligosaccharides by bifidobacterium breve in the premature infant[J]. J Pediatr Gastroenterol Nutr,2017,65(4):449-455.
[53] Dzidic M, Mira A, Artacho A, et al. Allergy development is associated with consumption of breastmilk with a reduced microbial richness in the first month of life[J]. Pediatr Allergy Immunol,2020,31(3):250-257.
[54] Riaz RM, Zhao H, Mehwish HM, et al. Anti-tumor potential of cell free culture supernatant of Lactobacillus rhamnosus strains isolated from human breast milk[J]. Food Res Int,2019,123:286-297.