母乳营养成分与早产儿脑发育的研究进展
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摘要
母乳是早产儿的首选食品。近年来,母乳在早产儿脑发育中的作用越来越多地受到学者重视。研究表明,母乳喂养对早产儿神经发育、远期认知结果的影响可能一直持续到儿童、青少年,甚至成人时期。母乳中的营养成分在其中起着决定性作用,涉及低聚糖、多不饱和脂肪酸、乳铁蛋白等。该文将母乳中营养成分在早产儿脑发育中的最新研究进展作一综述,具体阐述每种营养成分的概念和作用。[中国当代儿科杂志,2019,21(6):607-612]
Breast milk is the preferred food for preterm infants. In recent years, the role of breast milk in the brain development of preterm infants has attracted more and more attention. Studies have shown that the effect of breastfeeding on neurodevelopment and long-term cognitive outcome of preterm infants may persist into childhood, adolescence, and even adulthood. The nutrients in breast milk, such as oligosaccharides, polyunsaturated fatty acids, and lactoferrin, play an important role in this process. This article reviews the latest research advances in the role of breast milk nutrients in the brain development of preterm infants and elaborates on the concept and function of each nutrient.[Chin J Contemp Pediatr, 2019, 21(6): 607-612]
Breast milk is the preferred food for preterm infants. In recent years, the role of breast milk in the brain development of preterm infants has attracted more and more attention. Studies have shown that the effect of breastfeeding on neurodevelopment and long-term cognitive outcome of preterm infants may persist into childhood, adolescence, and even adulthood. The nutrients in breast milk, such as oligosaccharides, polyunsaturated fatty acids, and lactoferrin, play an important role in this process. This article reviews the latest research advances in the role of breast milk nutrients in the brain development of preterm infants and elaborates on the concept and function of each nutrient.[Chin J Contemp Pediatr, 2019, 21(6): 607-612]
引文
[1]Kuchenbecker J,Jordan I,Reinbott A,et al.Exclusive breastfeeding and its effect on growth of Malawian infants:results from a cross-sectional study[J].Paediatr Int Child Health,2015,35(1):14-23.
[2]Belfort MB,Anderson PJ,Nowak VA,et al.Breast milk feeding,brain development,and neurocognitive outcomes:a7-year longitudinal study in infants born at less than 30 weeks'gestation[J].J Pediatr,2016,177:133-139.e1.
[3]Victora CG,Horta BL,Loret de Mola C,et al.Association between breastfeeding and intelligence,educational attainment,and income at 30 years of age:a prospective birth cohort study from Brazil[J].Lancet Glob Health,2015,3(4):e199-e205.
[4]Deoni SC,Dean DC 3rd,Piryatinsky I,et al.Breastfeeding and early white matter development:a cross-sectional study[J].Neuroimage,2013,82:77-86.
[5]MontiL,Cattaneo TM,Orlandi M,et al.Capillary electrophoresis of sialylated oligosaccharides in milk from different species[J].J Chromatogr A,2015,1409:288-291.
[6]Charbonneau MR,O'Donnell D,Blanton LV,et al.Sialylated milk oligosaccharides promote microbiota-dependent growth in models of infant undernutrition[J].Cell,2016,164(5):859-871.
[7]Garrido D,Ruiz-Moyano S,Kirmiz N,et al.A novel gene cluster allows preferential utilization of fucosylated milk oligosaccharides in Bifidobacterium longum subsp.longum SC596[J].Sci Rep,2016,6:35045.
[8]Davis JC,Lewis ZT,Krishnan S,et al.Growth and morbidity of gambian infants are influenced by maternal milk oligosaccharides and infant gut microbiota[J].Sci Rep,2017,7:40466.
[9]Bunesova V,Lacroix C,Schwab C.Mucin cross-feeding of infant Bifidobacteria and Eubacterium hallii[J].Microb Ecol,2018,75(1):228-238.
[10]Foster JA,Lyte M,Meyer E,et al.Gut microbiota and brain function:an evolving field in neuroscience[J].Int JNeuropsychopharmacol,2016,19(5):pyv114.
[11]Bode L.The functional biology of human milk oligosaccharides[J].Early Hum Dev,2015,91(11):619-622.
[12]Lin AE,Autran C A,Szyszka A,et al.Human milk oligosaccharides inhibit growth of group B[J].J Biol Chem,2017,292(27):11243-11249.
[13]Laucirica DR,Triantis V,Schoemaker R,et al.Milk oligosaccharides inhibit human rotavirus infectivity in MA104cells[J].J Nutr,2017,147(9):1709-1714.
[14]Cilieborg MS,Sangild PT,Jensen ML,et al.α1,2-fucosyllactose does not improve intestinal function or prevent Escherichia coli F18 diarrhea in newborn pigs[J].J Pediatr Gastroenterol Nutr,2017,64(2):310-318.
[15]Goehring KC,Kennedy AD,Prieto PA,et al.Direct evidence for the presence of human milk oligosaccharides in the circulation of breastfed infants[J].PLoS One,2014,9(7):e101692.
[16]Noll AJ,Yu Y,Lasanajak Y,et al.Human DC-SIGN binds specific human milk glycans[J].Biochem J,2016,473(10):1343-1353.
[17]He Y,Liu S,Kling DE,et al.The human milk oligosaccharide2'-fucosyllactose modulates CD14 expression in human enterocytes,thereby attenuating LPS-induced inflammation[J].Gut,2016,65(1):33-46.
[18]Feldman D E.Synaptic mechanisms for plasticity in neocortex[J].Annu Rev Neurosci,2009,32:33-55.
[19]Vázquez E,Barranco A,Ramírez M,et al.Effects of a human milk oligosaccharide,2'-fucosyllactose,on hippocampal longterm potentiation and learning capabilities in rodents[J].J Nutr Biochem,2015,26(5):455-465.
[20]Oliveros E,Ramirez M,Vazquez E,et al.Oral supplementation of 2'-fucosyllactose during lactation improves memory and learning in rats[J].J Nutr Biochem,2016,31:20-27.
[21]Vazquez E,Barranco A,Ramirez M,et al.Dietary2'-fucosyllactose enhances operant conditioning and long-term potentiation via gut-brain communication through the vagus nerve in rodents[J].PLoS One,2016,11(11):e0166070.
[22]Schengrund CL.Gangliosides:glycosphingolipids essential for normal neural development and function[J].Trends Biochem Sci,2015,40(7):397-406.
[23]Schnaar RL,Gerardy-Schahn R,Hildebrandt H.Sialic acids in the brain:gangliosides and polysialic acid in nervous system development,stability,disease,and regeneration[J].Physiol Rev,2014,94(2):461-518.
[24]Jacobi SK,Yatsunenko T,Li D,et al.Dietary isomers of sialyllactose increase canglioside sialic acid concentrations in the corpus callosum and cerebellum and modulate the colonic microbiota of formula-fed piglets[J].J Nutr,2016,146(2):200-208.
[25]González HF,Visentin S.Nutrients and neurodevelopment:lipids[J].Arch Argent Pediatr,2016,114(5):472-476.
[26]Carlson SE,Colombo J.Docosahexaenoic acid and arachidonic acid nutrition in early development[J].Adv Pediatr,2016,63(1):453-471.
[27]Weiser MJ,Butt CM,Mohajeri MH.Docosahexaenoic acid and cognition throughout the lifespan[J].Nutrients,2016,8(2):99.
[28]Lepping RJ,Honea RA,Martin LE,et al.Long-chain polyunsaturated fatty acid supplementation in the first year of life affects brain function,structure,and metabolism at age nine years[J].Dev Psychobiol,2019,61(1):5-16.
[29]Lassek WD,Gaulin SJ.Maternal milk DHA content predicts cognitive performance in a sample of 28 nations[J].Matern Child Nutr,2015,11(4):773-779.
[30]Richard C,Calder PC.Docosahexaenoic acid[J].Adv Nutr,2016,7(6):1139-1141.
[31]Calder PC.Very long-chain n-3 fatty acids and human health:fact,fiction and the future[J].Proc Nutr Soc,2018,77(1):52-72.
[32]He C,Qu X,Cui L,et al.Improved spatial learning performance of fat-1 mice is associated with enhanced neurogenesis and neuritogenesis by docosahexaenoic acid[J].Proc Natl Acad Sci U S A,2009,106(27):11370-11375.
[33]Cao D,Kevala K,Kim J,et al.Docosahexaenoic acid promotes hippocampal neuronal development and synaptic function[J].JNeurochem,2009,111(2):510-521.
[34]Gharami K,Das M,Das S.Essential role of docosahexaenoic acid towards development of a smarter brain[J].Neurochem Int,2015,89:51-62.
[35]Salvati S,Natali F,Attorri L,et al.Eicosapentaenoic acid stimulates the expression of myelin proteins in rat brain[J].JNeurosci Res,2008,86(4):776-784.
[36]Calder PC.Marine omega-3 fatty acids and inflammatory processes:effects,mechanisms and clinical relevance[J].Biochim Biophys Acta,2015,1851(4):469-484.
[37]Duvall MG,Levy BD.DHA-and EPA-derived resolvins,protectins,and maresins in airway inflammation[J].Eur JPharmacol,2016,785:144-155.
[38]P a r k T,C h e n H,K e v a l a K,e t a l.N-D o c o s a h e x a enoylethanolamine ameliorates LPS-induced neuroinflammation via cAMP/PKA-dependent signaling[J].J Neuroinflammation,2016,13(1):284.
[39]Wang L,Luo G,Zhang LF,et al.Neuroprotective effects of epoxyeicosatrienoic acids[J].Prostaglandins Other Lipid Mediat,2018,138:9-14.
[40]Cai X,Duan Y,Li Y,et al.Lactoferrin level in breast milk:a study of 248 samples from eight regions in China[J].Food Funct,2018,9(8):4216-4222.
[41]Ochoa TJ,Zegarra J,Cam L,et al.Randomized controlled trial of lactoferrin for prevention of sepsis in peruvian neonates less than 2500 g[J].Pediatr Infect Dis J,2015,34(6):571-576.
[42]Reznikov EA,Comstock SS,Hoeflinger JL,et al.Dietary bovine lactoferrin reduces Staphylococcus aureus in the tissues and modulates the immune response in piglets systemically infected with S.aureus[J].Curr Dev Nutr,2017,2(4):nzy001.
[43]Woodman T,Strunk T,Patole S,et al.Effects of lactoferrin on neonatal pathogens and Bifidobacterium breve in human breast milk[J].PLoS One,2018,13(8):e0201819.
[44]Wang B,Timilsena YP,Blanch E,et al.Lactoferrin:structure,function,denaturation and digestion[J].Crit Rev Food Sci Nutr,2017:1-17.
[45]Parrón JA,Ripollés D,Ramos SJ,et al.Antirotaviral potential of lactoferrin from different origin:effect of thermal and high pressure treatments[J].Biometals,2018,31(3):343-355.
[46]Congdon EL,Westerlund A,Algarin CR,et al.Iron deficiency in infancy is associated with altered neural correlates of recognition memory at 10 years[J].J Pediatr,2012,160(6):1027-1033.
[47]L?nnerdal B,Georgieff MK,Hernell O.Developmental physiology of iron absorption,homeostasis,and metabolism in the healthy term infant[J].J Pediatr,2015,167(4 Suppl):S8-S14.
[48]Wang B.Molecular determinants of milk lactoferrin as a bioactive compound in early neurodevelopment and cognition[J].J Pediatr,2016,173 Suppl:S29-S36.
[49]Chen Y,Zheng Z,Zhu X,et al.Lactoferrin promotes early neurodevelopment and cognition in postnatal piglets by upregulating the BDNF signaling pathway and polysialylation[J].Mol Neurobiol,2015,52(1):256-269.
[50]Somm E,Larvaron P,van de Looij Y,et al.Protective effects of maternal nutritional supplementation with lactoferrin on growth and brain metabolism[J].Pediatr Res,2014,75(1-1):51-61.
[51]Ginet V,van de Looij Y,Petrenko V,et al.Lactoferrin during lactation reduces lipopolysaccharide-induced brain injury[J].Biofactors,2016,42(3):323-336.
[52]van de Looij Y,Ginet V,Chatagner A,et al.Lactoferrin during lactation protects the immature hypoxic-ischemic rat brain[J].Ann Clin Transl Neurol,2014,1(12):955-967.
[53]Ochoa TJ,Sizonenko SV.Lactoferrin and prematurity:a promising milk protein?[J].Biochem Cell Biol,2017,95(1):22-30.
[2]Belfort MB,Anderson PJ,Nowak VA,et al.Breast milk feeding,brain development,and neurocognitive outcomes:a7-year longitudinal study in infants born at less than 30 weeks'gestation[J].J Pediatr,2016,177:133-139.e1.
[3]Victora CG,Horta BL,Loret de Mola C,et al.Association between breastfeeding and intelligence,educational attainment,and income at 30 years of age:a prospective birth cohort study from Brazil[J].Lancet Glob Health,2015,3(4):e199-e205.
[4]Deoni SC,Dean DC 3rd,Piryatinsky I,et al.Breastfeeding and early white matter development:a cross-sectional study[J].Neuroimage,2013,82:77-86.
[5]MontiL,Cattaneo TM,Orlandi M,et al.Capillary electrophoresis of sialylated oligosaccharides in milk from different species[J].J Chromatogr A,2015,1409:288-291.
[6]Charbonneau MR,O'Donnell D,Blanton LV,et al.Sialylated milk oligosaccharides promote microbiota-dependent growth in models of infant undernutrition[J].Cell,2016,164(5):859-871.
[7]Garrido D,Ruiz-Moyano S,Kirmiz N,et al.A novel gene cluster allows preferential utilization of fucosylated milk oligosaccharides in Bifidobacterium longum subsp.longum SC596[J].Sci Rep,2016,6:35045.
[8]Davis JC,Lewis ZT,Krishnan S,et al.Growth and morbidity of gambian infants are influenced by maternal milk oligosaccharides and infant gut microbiota[J].Sci Rep,2017,7:40466.
[9]Bunesova V,Lacroix C,Schwab C.Mucin cross-feeding of infant Bifidobacteria and Eubacterium hallii[J].Microb Ecol,2018,75(1):228-238.
[10]Foster JA,Lyte M,Meyer E,et al.Gut microbiota and brain function:an evolving field in neuroscience[J].Int JNeuropsychopharmacol,2016,19(5):pyv114.
[11]Bode L.The functional biology of human milk oligosaccharides[J].Early Hum Dev,2015,91(11):619-622.
[12]Lin AE,Autran C A,Szyszka A,et al.Human milk oligosaccharides inhibit growth of group B[J].J Biol Chem,2017,292(27):11243-11249.
[13]Laucirica DR,Triantis V,Schoemaker R,et al.Milk oligosaccharides inhibit human rotavirus infectivity in MA104cells[J].J Nutr,2017,147(9):1709-1714.
[14]Cilieborg MS,Sangild PT,Jensen ML,et al.α1,2-fucosyllactose does not improve intestinal function or prevent Escherichia coli F18 diarrhea in newborn pigs[J].J Pediatr Gastroenterol Nutr,2017,64(2):310-318.
[15]Goehring KC,Kennedy AD,Prieto PA,et al.Direct evidence for the presence of human milk oligosaccharides in the circulation of breastfed infants[J].PLoS One,2014,9(7):e101692.
[16]Noll AJ,Yu Y,Lasanajak Y,et al.Human DC-SIGN binds specific human milk glycans[J].Biochem J,2016,473(10):1343-1353.
[17]He Y,Liu S,Kling DE,et al.The human milk oligosaccharide2'-fucosyllactose modulates CD14 expression in human enterocytes,thereby attenuating LPS-induced inflammation[J].Gut,2016,65(1):33-46.
[18]Feldman D E.Synaptic mechanisms for plasticity in neocortex[J].Annu Rev Neurosci,2009,32:33-55.
[19]Vázquez E,Barranco A,Ramírez M,et al.Effects of a human milk oligosaccharide,2'-fucosyllactose,on hippocampal longterm potentiation and learning capabilities in rodents[J].J Nutr Biochem,2015,26(5):455-465.
[20]Oliveros E,Ramirez M,Vazquez E,et al.Oral supplementation of 2'-fucosyllactose during lactation improves memory and learning in rats[J].J Nutr Biochem,2016,31:20-27.
[21]Vazquez E,Barranco A,Ramirez M,et al.Dietary2'-fucosyllactose enhances operant conditioning and long-term potentiation via gut-brain communication through the vagus nerve in rodents[J].PLoS One,2016,11(11):e0166070.
[22]Schengrund CL.Gangliosides:glycosphingolipids essential for normal neural development and function[J].Trends Biochem Sci,2015,40(7):397-406.
[23]Schnaar RL,Gerardy-Schahn R,Hildebrandt H.Sialic acids in the brain:gangliosides and polysialic acid in nervous system development,stability,disease,and regeneration[J].Physiol Rev,2014,94(2):461-518.
[24]Jacobi SK,Yatsunenko T,Li D,et al.Dietary isomers of sialyllactose increase canglioside sialic acid concentrations in the corpus callosum and cerebellum and modulate the colonic microbiota of formula-fed piglets[J].J Nutr,2016,146(2):200-208.
[25]González HF,Visentin S.Nutrients and neurodevelopment:lipids[J].Arch Argent Pediatr,2016,114(5):472-476.
[26]Carlson SE,Colombo J.Docosahexaenoic acid and arachidonic acid nutrition in early development[J].Adv Pediatr,2016,63(1):453-471.
[27]Weiser MJ,Butt CM,Mohajeri MH.Docosahexaenoic acid and cognition throughout the lifespan[J].Nutrients,2016,8(2):99.
[28]Lepping RJ,Honea RA,Martin LE,et al.Long-chain polyunsaturated fatty acid supplementation in the first year of life affects brain function,structure,and metabolism at age nine years[J].Dev Psychobiol,2019,61(1):5-16.
[29]Lassek WD,Gaulin SJ.Maternal milk DHA content predicts cognitive performance in a sample of 28 nations[J].Matern Child Nutr,2015,11(4):773-779.
[30]Richard C,Calder PC.Docosahexaenoic acid[J].Adv Nutr,2016,7(6):1139-1141.
[31]Calder PC.Very long-chain n-3 fatty acids and human health:fact,fiction and the future[J].Proc Nutr Soc,2018,77(1):52-72.
[32]He C,Qu X,Cui L,et al.Improved spatial learning performance of fat-1 mice is associated with enhanced neurogenesis and neuritogenesis by docosahexaenoic acid[J].Proc Natl Acad Sci U S A,2009,106(27):11370-11375.
[33]Cao D,Kevala K,Kim J,et al.Docosahexaenoic acid promotes hippocampal neuronal development and synaptic function[J].JNeurochem,2009,111(2):510-521.
[34]Gharami K,Das M,Das S.Essential role of docosahexaenoic acid towards development of a smarter brain[J].Neurochem Int,2015,89:51-62.
[35]Salvati S,Natali F,Attorri L,et al.Eicosapentaenoic acid stimulates the expression of myelin proteins in rat brain[J].JNeurosci Res,2008,86(4):776-784.
[36]Calder PC.Marine omega-3 fatty acids and inflammatory processes:effects,mechanisms and clinical relevance[J].Biochim Biophys Acta,2015,1851(4):469-484.
[37]Duvall MG,Levy BD.DHA-and EPA-derived resolvins,protectins,and maresins in airway inflammation[J].Eur JPharmacol,2016,785:144-155.
[38]P a r k T,C h e n H,K e v a l a K,e t a l.N-D o c o s a h e x a enoylethanolamine ameliorates LPS-induced neuroinflammation via cAMP/PKA-dependent signaling[J].J Neuroinflammation,2016,13(1):284.
[39]Wang L,Luo G,Zhang LF,et al.Neuroprotective effects of epoxyeicosatrienoic acids[J].Prostaglandins Other Lipid Mediat,2018,138:9-14.
[40]Cai X,Duan Y,Li Y,et al.Lactoferrin level in breast milk:a study of 248 samples from eight regions in China[J].Food Funct,2018,9(8):4216-4222.
[41]Ochoa TJ,Zegarra J,Cam L,et al.Randomized controlled trial of lactoferrin for prevention of sepsis in peruvian neonates less than 2500 g[J].Pediatr Infect Dis J,2015,34(6):571-576.
[42]Reznikov EA,Comstock SS,Hoeflinger JL,et al.Dietary bovine lactoferrin reduces Staphylococcus aureus in the tissues and modulates the immune response in piglets systemically infected with S.aureus[J].Curr Dev Nutr,2017,2(4):nzy001.
[43]Woodman T,Strunk T,Patole S,et al.Effects of lactoferrin on neonatal pathogens and Bifidobacterium breve in human breast milk[J].PLoS One,2018,13(8):e0201819.
[44]Wang B,Timilsena YP,Blanch E,et al.Lactoferrin:structure,function,denaturation and digestion[J].Crit Rev Food Sci Nutr,2017:1-17.
[45]Parrón JA,Ripollés D,Ramos SJ,et al.Antirotaviral potential of lactoferrin from different origin:effect of thermal and high pressure treatments[J].Biometals,2018,31(3):343-355.
[46]Congdon EL,Westerlund A,Algarin CR,et al.Iron deficiency in infancy is associated with altered neural correlates of recognition memory at 10 years[J].J Pediatr,2012,160(6):1027-1033.
[47]L?nnerdal B,Georgieff MK,Hernell O.Developmental physiology of iron absorption,homeostasis,and metabolism in the healthy term infant[J].J Pediatr,2015,167(4 Suppl):S8-S14.
[48]Wang B.Molecular determinants of milk lactoferrin as a bioactive compound in early neurodevelopment and cognition[J].J Pediatr,2016,173 Suppl:S29-S36.
[49]Chen Y,Zheng Z,Zhu X,et al.Lactoferrin promotes early neurodevelopment and cognition in postnatal piglets by upregulating the BDNF signaling pathway and polysialylation[J].Mol Neurobiol,2015,52(1):256-269.
[50]Somm E,Larvaron P,van de Looij Y,et al.Protective effects of maternal nutritional supplementation with lactoferrin on growth and brain metabolism[J].Pediatr Res,2014,75(1-1):51-61.
[51]Ginet V,van de Looij Y,Petrenko V,et al.Lactoferrin during lactation reduces lipopolysaccharide-induced brain injury[J].Biofactors,2016,42(3):323-336.
[52]van de Looij Y,Ginet V,Chatagner A,et al.Lactoferrin during lactation protects the immature hypoxic-ischemic rat brain[J].Ann Clin Transl Neurol,2014,1(12):955-967.
[53]Ochoa TJ,Sizonenko SV.Lactoferrin and prematurity:a promising milk protein?[J].Biochem Cell Biol,2017,95(1):22-30.