Graphical Abstract
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Breast milk is the preferred gold standard food for infants. Human milk oligosaccharides (HMOs) are the third most natural component in breast milk. But breast milk is often insufficient, so they rely solely on breast milk substitutes. HMOs provide nutrients to beneficial gut microbiota such as Lactobacilli and Bifidobacteria, helping to establish and maintain a balance of microbial communities in the infant gut. HMOs mimic the receptors of pathogens, preventing them from attaching to the baby’s intestinal cells, thereby preventing pathogen infection. This function is particularly crucial for newborns and infants. How to individually use HMOs is important. We focused on classification and characteristics of HMOs, their impact, intake, development/utilization mechanism on infant health, aiming to provide HMOs data support for the development. HMOs are quite different (more than 200 kinds), so it is necessary to make targeted selection, and those associated with intestinal microorganisms (Bifidobacterium), which can utilize HMOs, have the greatest application potential. Oligosaccharide-binding protein (OBPs) are an important medium for ATP-binding cassette transporter channel of intestinal HMOs transport; the influence of key OBPs of Bifidobacterium on HMOs recognition in infants from various countries has been explored, which is helpful to accelerate the establishment of precise and personalized milk powder in the future. The more important significance of the results of this review is to help consumers better choose HMOs, thereby promoting the long-term health of infants, especially the early development of their immune system.
Y. P. Wang, A. Q. Ye, Y. Y. Hou, et al., Microcapsule delivery systems of functional ingredients in infant formulae: research progress, technology, and feasible application of liposomes, Trends Food Sci. Tech. 119 (2022) 36–44. https://doi.org/10.1016/ j.jpgs.2021.11.016.
G. J. Ahern, A. A. Hennessy, C. A. Ryan, et al., Advances in infant formula science, Annu. Rev. Food Sci. Technol. 10 (2019) 75–102. https://doi.org/10.1146/annurev-food-081318-104308.
T. T. Bu, J. X. Zheng, L. Liu, et al., Milk proteins and their derived peptides on bone health: biological functions, mechanisms, and prospects, Compr. Rev. Food Sci. Saf. 20(2) (2021) 2234–2262. https://doi.org/10.1111/1541-4337.12707.
W. Wei, X. Y. Hu, Z. Z. Hou, et al., Microbial community structure and diversity in different types of non-bovine milk, Curr. Opin. Food Sci. 40 (2021) 51–57. https://doi.org/10.1016/j.cofs.2021.01.008.
S. Bashiardes, C. A. Thaiss, E. Elinav, It’s in the milk: feeding the microbiome to promote infant growth, Cell Metab. 23(3) (2016) 393–394. https://doi.org/10.1016/j.cmet.2016.02.015.
K. Karcz, B. Krolak-Olejnik, Vegan or vegetarian diet and breast milk composition: a systematic review, Crit. Rev. Food Sci. 61(7) (2021) 1081–1098. https://doi.org/10.1080/10408398.2020.1753650.
M. E Miettinen, J. Honkanen, S. Niinistö, et al., Breastfeeding and circulating immunological markers during the first 3 years of life: the DIABIMMUNE study, Diabetologia 65(2) (2022) 329–335. https://doi.org/10.1007/s00125-021-05612-2.
H. Pahwa, K. Sharan, Food and nutrition as modifiers of the immune system: a mechanistic overview, Trends Food Sci. Tech. 123 (2022) 393–403. https://doi.org/10.1016/j.jpgs.2022.03.017.
I. Wessels, H. J. Fischer, L. Rink, Dietary and physiological effects of zinc on the immune system, Annu. Rev. Nutr. 41 (2021) 133–175. https://doi.org/10.1146/annurev-nutr-122019-120635.
D. M. Wu, X. Q. Ye, R. J. Linhardt, et al., Dietary pectic substances enhance gut health by its polycomponent: a review, Compr. Rev. Food Sci. Saf. 20(2) (2021) 2015–2039. https://doi.org/10.1111/1541-4337.12723.
L. E. Carr, M. D. Virmani, F. Rosa, et al., Role of human milk bioactives on infants’ gut and immune health, Front. Immunol. 12 (2021) 604080. https://doi.org/10.3389/fimmu.2021.604080.
L. Duijts, V. W. V. Jaddoe, A. Hofman, et al., Prolonged and exclusive breastfeeding reduces the risk of infectious diseases in infancy, Pediatrics 126(1) (2010) E18–E25. https://doi.org/10.1542/peds.2008-3256.
S. Haroon, J. K. Das, R. A. Salam, et al., Breastfeeding promotion interventions and breastfeeding practices: a systematic review, BMC Public Health 13 (2013) S20. https://doi.org/10.1186/1471-2458-13-S3-S20.
J. W. Meng, Y. Y. Zhu, H. Wang, et al., Biosynthesis of human milk oligosaccharides: enzyme cascade and metabolic engineering approaches, J. Agric. Food Chem. 71(5) (2023) 2234–2243. https://doi.org/10.1021/acs.jafc.2c08436.
M. M. Hu, M. L. Li, C. C. Li, et al., Effects of human milk oligosaccharides in infant health based on gut microbiota alteration, J. Agric. Food Chem. 71(2) (2023) 994–1001. https://doi.org/10.1021/acs.jafc.2c05734.
E. Perez-Escalante, S. Alatorre-Santamaria, A. Castaneda-Ovando, et al., Human milk oligosaccharides as bioactive compounds in infant formula: recent advances and trends in synthetic methods, Crit. Rev. Food Sci. 62(1) (2022) 181–214. https://doi.org/10.1080/10408398.2020.1813683.
L. H. Cheng, R. Akkerman, C. L. Kong, et al., More than sugar in the milk: human milk oligosaccharides as essential bioactive molecules in breast milk and current insight in beneficial effects, Crit. Rev. Food Sci. 61(7) (2021) 1184–1200. https://doi.org/10.1080/10408398.2020.1754756.
M. Chichlowski, J. B. German, C. B. Lebrilla, et al., The influence of milk oligosaccharides on microbiota of infants: opportunities for formulas, Annu. Rev. Food Sci. T. 2 (2011) 331–351. https://doi.org/10.1146/annurev-food-022510-133743.
F. Y. Meng, T. Uniacke-Lowe, A. C. Ryan, et al., The composition and physico-chemical properties of human milk: a review, Trends Food Sci. Tech. 112 (2021) 608–621. https://doi.org/10.1016/j.jpgs.2021.03.040.
C. Vera, A. Illanes, C. Guerrero, Enzymatic production of prebiotic oligosaccharides, Curr. Opin. Food Sci. 37 (2021) 160–170. https://doi.org/10.1016/j.cofs.2020.10.013.
Y. Wang, J. H. Yu, Membrane separation processes for enrichment of bovine and caprine milk oligosaccharides from dairy byproducts, Compr. Rev. Food Sci. Saf. 20(4) (2021) 3667–3689. https://doi.org/10.1111/1541-4337.12758.
C. C. Qin, L. Liu, Y. Wang, et al., Advancement of omics techniques for chemical profile analysis and authentication of milk, Trends Food Sci. Tech. 127 (2022) 114–128. https://doi.org/10.1016/j.jpgs.2022.06.001.
J. P. Chouraqui, Does the contribution of human milk oligosaccharides to the beneficial effects of breast milk allow us to hope for an improvement in infant formulas?, Crit. Rev. Food Sci. 61(9) (2021) 1503–1514. https://doi.org/10.1080/10408398.2020.1761772.
C. Fischer, T. Kleinschmidt, Synthesis of galactooligosaccharides in milk and whey: a review, Compr. Rev. Food Sci. Saf. 17(3) (2018) 678–697. https://doi.org/10.1111/1541-4337.12344.
J. A. Hong, J. Y. Chang, S. Oh, The current status of prolonged breastfeeding and its related factors in Korean infants and their mothers: a nationwide cross-sectional study, J. Korean Med. Sci. 38(33) (2023) e261. https://doi.org/10.3346/jkms.2023.38.e261.
S. S. Van Leeuwen, E. M. Te Poele, A. C. Chatziioannou, et al., Goat milk oligosaccharides: their diversity, quantity, and functional properties in comparison to human milk oligosaccharides, J. Agric. Food Chem. 68(47) (2020) 13469–13485. https://doi.org/10.1021/acs.jafc.0c03766.
A. S. Christensen, S. H. Skov, S. E. Lendal, et al., Quantifying the human milk oligosaccharides 2’-fucosyllactose and 3-fucosyllactose in different food applications by high-performance liquid chromatography with refractive index detection, J. Food Sci. 85(2) (2020) 332–339. https://doi.org/10.1111/1750-3841.15005.
V. Morozov, G. Hansman, F. G. Hanisch, et al., Human milk oligosaccharides as promising antivirals, Mol. Nutr. Food Res. 62(6) (2018) e1700679. https://doi.org/10.1002/mnfr.201700679.
J. T. Smilowitz, C. B. Lebrilla, D. A. Mills, et al., Breast milk oligosaccharides: structure-function relationships in the neonate, Annu. Rev. Nutr. 34 (2014) 143–169. https://doi.org/10.1146/annurev-nutr-071813-105721.
L. Bode, The functional biology of human milk oligosaccharides, Early Hum. Dev. 91(11) (2015) 619–622. https://doi.org/10.1016/j.earlhumdev.2015.09.001.
C. Walsh, J. A. Lane, D. Van Sinderen, et al., From lab bench to formulated ingredient: characterization, production, and commercialization of human milk oligosaccharides, J. Funct. Foods 72 (2020) 104052. https://doi.org/10.1016/j.jff.2020.104052.
X. Chen, Human milk oligosaccharides (HMOS): structure, function, and enzyme-catalyzed synthesis, Adv. Carbohyd. Chem. Biochem. 72 (2015) 113–190. https://doi.org/10.1016/bs.accb.2015.08.002.
J. E. Williams, M. K. McGuire, C. L. Meehan, et al., Key genetic variants associated with variation of milk oligosaccharides from diverse human populations, Genomics 113(4) (2021) 1867–1875. https://doi.org/10.1016/j.ygeno.2021.04.004.
D. Blank, V. Dotz, R. Geyer, et al., Human milk oligosaccharides and Lewis blood group: individual high-throughput sample profiling to enhance conclusions from functional studies, Adv. Nutr. 3(3) (2012) 440s–449s. https://doi.org/10.3945/an.111.001446.
S. Thurl, M. Munzert, J. Henker, et al., Variation of human milk oligosaccharides in relation to milk groups and lactational periods, Brit. J. Nutr. 104(9) (2010) 1261–1271. https://doi.org/10.1017/S0007114510002072.
M. K. McGuire, C. L. Meehan, M. A. McGuire, et al., What’s normal? Oligosaccharide concentrations and profiles in milk produced by healthy women vary geographically, Am. J. Clin. Nutr. 105(5) (2017) 1086–1100. https://doi.org/10.3945/ajcn.116.139980.
L. Bode, L. Kuhn, H. Y. Kim, et al., Human milk oligosaccharide concentration and risk of postnatal transmission of HIV through breastfeeding, Am. J. Clin. Nutr. 96(4) (2012) 831–839. https://doi.org/10.3945/ajcn.112.039503.
D. R. Laucirica, V. Triantis, R. Schoemaker, et al., Milk oligosaccharides inhibit human rotavirus infectivity in MA104 cells, J. Nutr. 147(9) (2017) 1709–1714. https://doi.org/10.3945/jn.116.246090.
B. Facinelli, E. Marini, G. Magi, et al., Breast milk oligosaccharides: effects of 2’-fucosyllactose and 6’-sialyllactose on the adhesion of and to Caco-2 cells, J. Matern. Fetal. Neonatal. Med. 32(17) (2019) 2950–2952. https://doi.org/10.1080/14767058.2018.1450864.
C. A. Autran, B. P. Kellman, J. H. Kim, et al., Human milk oligosaccharide composition predicts risk of necrotising enterocolitis in preterm infants, Gut 67(6) (2018) 1064–1070. https://doi.org/10.1136/gutjnl-2016-312819.
R. M. Nijman, Y. Liu, A. Bunyatratchata, et al., Characterization and quantification of oligosaccharides in human milk and infant formula, J. Agric. Food Chem. 66(26) (2018) 6851–6859. https://doi.org/10.1021/acs.jafc.8b01515.
W. Y. Zhang, T. Wang, X. X. Chen, et al., Absolute quantification of twelve oligosaccharides in human milk using a targeted mass spectrometry-based approach, Carbohyd. Polym. 219 (2019) 328–333. https://doi.org/10.1016/j.carbpol.2019.04.092.
F. Galeotti, G. V. Coppa, L. Zampini, et al., Capillary electrophoresis separation of human milk neutral and acidic oligosaccharides derivatized with 2-aminoacridone, Electrophoresis 35(6) (2014) 811–818. https://doi.org/10.1002/elps.201300490.
S. S. van Leeuwen, Rapid milk group classification by 1H NMR analysis of Le and H epitopes in human milk oligosaccharide donor samples, Glycobiology 24(8) (2014) 728–739. https://doi.org/10.1093/glycob/cwu036.
R. Kaur, K. Prasad, Technological, processing and nutritional aspects of chickpea ( Cicer arietinum): a review, Trends Food Sci. Tech. 109 (2021) 448–463. https://doi.org/10.1016/j.jpgs.2021.01.044.
Y. H. Cui, X. J. Qu, Genetic mechanisms of prebiotic carbohydrate metabolism in lactic acid bacteria: emphasis on Lacticaseibacillus casei and Lacticaseibacillus paracasei as flexible, diverse and outstanding prebiotic carbohydrate starters, Trends Food Sci. Tech. 115 (2021) 486–499. https://doi.org/10.1016/j.jpgs.2021.06.058.
C. Grootaert, J. A. Delcour, C. M. Courtin, et al., Microbial metabolism and prebiotic potency of arabinoxylan oligosaccharides in the human intestine, Trends Food Sci. Tech. 18(2) (2007) 64–71. https://doi.org/10.1016/j.jpgs.2006.08.004.
C. L. Schengrund, Gangliosides: glycosphingolipids essential for normal neural development and function, Trends Biochem. Sci. 40(7) (2015) 397–406. https://doi.org/10.1016/j.tibs.2015.03.007.
R. L. Schnaar, R. Gerardy-Schahn, H. Hildebrandt, Sialic acids in the brain: gangliosides and polysialic acid in nervous system development, stability, disease, and regeneration, Physiol. Rev. 94(2) (2014) 461–518. https://doi.org/10.1152/physrev.00033.2013.
S. K. Jacobi, T. Yatsunenko, D. P. Li, et al., Dietary isomers of sialyllactose increase ganglioside sialic acid concentrations in the corpus callosum and cerebellum and modulate the colonic microbiota of formula-fed piglets, J. Nutr. 146(2) (2016) 200–208. https://doi.org/10.3945/jn.115.220152.
B. Wang, Molecular mechanism underlying sialic acid as an essential nutrient for brain development and cognition, Adv. Nutr. 3(3) (2012) 465s–472s. https://doi.org/10.3945/an.112.001875.
E. Oliveros, M. Ramirez, E. Vazquez, et al., Oral supplementation of 2’-fucosyllactose during lactation improves memory and learning in rats, J. Nutr. Biochem. 31 (2016) 20–27. https://doi.org/10.1016/j.jnutbio.2015.12.014.
M. Li, M. H. Monaco, M. Wang, et al., Human milk oligosaccharides shorten rotavirus-induced diarrhea and modulate piglet mucosal immunity and colonic microbiota, ISME J. 8(8) (2014) 1609–1620. https://doi.org/10.1038/ismej.2014.10.
S. Weichert, A. Koromyslova, B. K. Singh, et al., Structural basis for norovirus inhibition by human milk oligosaccharides, J. Virol. 90(9) (2016) 4843–4848. https://doi.org/10.1128/JVI.03223-15.
S. Etzold, L. Bode, Glycan-dependent viral infection in infants and the role of human milk oligosaccharides, Curr. Opin. Virol. 7 (2014) 101–107. https://doi.org/10.1016/j.coviro.2014.06.005.
L. Kuhn, H. Y. Kim, L. Hsiao, et al., Oligosaccharide composition of breast milk influences survival of uninfected children born to HIV-infected mothers in Lusaka, Zambia, J. Nutr. 145(1) (2015) 66–72. https://doi.org/10.3945/jn.114.199794.
L. Y. Hu, B. Sankaran, D. R. Laucirica, et al., Glycan recognition in globally dominant human rotaviruses, Nat. Commun. 9 (2018) 2631. https://doi.org/10.1038/s41467-018-05098-4.
S. R. Hintz, D. E. Kendrick, B. J. Stoll, et al., Neurodevelopmental and growth outcomes of extremely low birth weight infants after necrotizing enterocolitis, Pediatrics 115(3) (2005) 696–703. https://doi.org/10.1542/peds.2004-0569.
M. Wicinski, E. Sawicka, J. Gebalski, et al., Human milk oligosaccharides: health benefits, potential applications in infant formulas, and pharmacology, Nutrients 12(1) (2020) 266. https://doi.org/10.3390/nu12010266.
L. Bode, Human milk oligosaccharides: every baby needs a sugar mama, Glycobiology 22(9) (2012) 1147–1162. https://doi.org/10.1093/glycob/cws074.
K. C. Goehring, B. J. Marriage, J. S. Oliver, et al., Similar to those who are breastfed, infants fed a formula containing 2’-fucosyllactose have lower inflammatory cytokines in a randomized controlled trial, J. Nutr. 146(12) (2016) 2559–2566. https://doi.org/10.3945/jn.116.236919.
W. S. Li, J. X. Wang, Y. Y. Lin, et al., How far is it from infant formula to human milk? A look at the human milk oligosaccharides, Trends Food Sci. Tech. 118 (2021) 374–387. https://doi.org/10.1016/j.jpgs.2021.09.021.
A. Kulinich, L. Liu, Human milk oligosaccharides: the role in the fine-tuning of innate immune responses, Carbohyd. Res. 432 (2016) 62–70. https://doi.org/10.1016/j.carres.2016.07.009.
J. E. Button, C. A. Autran, A. L. Reens, et al., Dosing a synbiotic of human milk oligosaccharides and B. infantis leads to reversible engraftment in healthy adult microbiomes without antibiotics, Cell Host Microbe. 30(5) (2022) 712–725. https://doi.org/10.1016/ j.chom.2022.04.001.
M. J. Pichler, C. Yamada, B. Shuoker, et al., Butyrate producing colonic Clostridiales metabolise human milk oligosaccharides and cross feed on mucin via conserved pathways, Nat. Commun. 11(1) (2020) 3285. https://doi.org/10.1038/s41467-020-17075-x.
G. N. Bidart, J. Rodriguez-Diaz, G. Perez-Martinez, et al., The lactose operon from Lactobacillus casei is involved in the transport and metabolism of the human milk oligosaccharide core-2 N-acetyllactosamine, Sci. Rep. 8 (2018) 7152. https://doi.org/10.1038/s41598-018-25660-w.
C. Yamada, A. Gotoh, M. Sakanaka, et al., Molecular insight into evolution of symbiosis between breast-fed infants and a member of the human gut microbiome Bifidobacterium longum, Cell Chem. Biol. 24(4) (2017) 515–524. https://doi.org/10.1016/j.chembiol.2017.03.012.
S. Asakuma, E. Hatakeyama, T. Urashima, et al., Physiology of consumption of human milk oligosaccharides by infant gut-associated Bifidobacteria, J. Biol. Chem. 286(40) (2011) 34583–34592. https://doi.org/10.1074/jbc.M111.248138.
M. Wang, M. Li, S. Wu, et al., Fecal microbiota composition of breast-fed infants is correlated with human milk oligosaccharides consumed, J. Pediatr. Gastr. Nutr. 60(6) (2015) 825–833. https://doi.org/10.1097/Mpg.0000000000000752.
M. L. A. De Leoz, K. M. Kalanetra, N. A. Bokulich, 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. 14(1) (2015) 491–502. https://doi.org/10.1021/pr500759e.
S. F. Oh, T. Praveena, H. Song, et al., Host immunomodulatory lipids created by symbionts from dietary amino acids, Nature 600 (2021) 302–307. https://doi.org/10.1038/s41586-021-04083-0.
K. Hezaveh, R. S. Shinde, A. Klötgen, et al., Tryptophan-derived microbial metabolites activate the aryl hydrocarbon receptor in tumor-associated macrophages to suppress anti-tumor immunity, Immunity 55(2) (2022) 324–340. https://doi.org/10.1016/j.immuni.2022.01.006.
O. O. Coker, C. A. Liu, W. K. K. Wu, et al., Altered gut metabolites and microbiota interactions are implicated in colorectal carcinogenesis and can be non-invasive diagnostic biomarkers, Microbiome 10 (2022) 35. https://doi.org/10.1186/s40168-021-01208-5.
C. Axel, B. Brosnan, E. Zannini, et al., Antifungal activities of three different Lactobacillus species and their production of antifungal carboxylic acids in wheat sourdough, Appl. Microbiol Biot. 100(4) (2016) 1701–1711. https://doi.org/10.1007/s00253-015-7051-x.
B. A. Daisley, D. Koenig, K. Engelbrecht, et al., Emerging connections between gut microbiome bioenergetics and chronic metabolic diseases, Cell Rep. 37(10) (2021) 110087. https://doi.org/10.1016/j.celrep.2021.110087.
M. Sakanaka, A. Gotoh, K. Yoshida, et al., Varied Pathways of infant gut-associated Bifidobacterium to assimilate human milk oligosaccharides: prevalence of the gene set and its correlation with Bifidobacteria-rich microbiota formation, Nutrients 12(1) (2020) 71. https://doi.org/10.3390/nu12010071.
C. Schwab, M. Ganzle, Lactic acid bacteria fermentation of human milk oligosaccharide components, human milk oligosaccharides and galactooligosaccharides, FEMS Microbiol. Lett. 315(2) (2011) 141–148. https://doi.org/10.1111/j.1574-6968.2010.02185.x.
G. W. Tannock, B. Lawley, K. Munro, et al., Comparison of the compositions of the stool microbiotas of infants fed goat milk formula, cow milk-based formula, or breast milk, Appl. Environ. Microb. 79(9) (2013) 3040–3048. https://doi.org/10.1128/Aem.03910-12.
D. A. Medina, F. Pinto, A. Ovalle, et al., Prebiotics mediate microbial interactions in a consortium of the infant gut microbiome, Int. J. Mol. Sci. 18(10) (2017) 2095. https://doi.org/10.3390/ijms18102095.
A. Marcobal, J. L. Sonnenburg, Human milk oligosaccharide consumption by intestinal microbiota, Clin. Microbiol. Infec. 18 (2012) 12–15. https://doi.org/10.1111/j.1469-0691.2012.03863.x.
D. C. Ekiert, G. Bhabha, G. L. Isom, et al., Architectures of lipid transport systems for the bacterial outer membrane, Cell 169(2) (2017) 273–285. https://doi.org/10.1016/j.cell.2017.03.019.
M. Sakanaka, M. E. Hansen, A. Gotoh, et al., Evolutionary adaptation in fucosyllactose uptake systems supports bifidobacteria-infant symbiosis, Sci. Adv. 5(8) (2019) eaaw7696. https://doi.org/10.1126/sciadv.aaw7696.
M. N. Ojima, L. Jiang, A. A. Arzamasov, et al., Priority effects shape the structure of infant-type Bifidobacterium communities on human milk oligosaccharides, ISME J. 16(9) (2022) 2265–2279. https://doi.org/10.1038/s41396-022-01270-3.
B. P. Kellman, A. Richelle, J. Y. Yang, et al., Elucidating human milk oligosaccharide biosynthetic genes through network-based multi-omics integration, Nat. Commun. 13(1) (2022) 2455. https://doi.org/10.1038/s41467-022-29867-4.
J. C. C. Davis, Z. T. Lewis, S. Krishnan, et al., Growth and morbidity of gambian infants are influenced by maternal milk oligosaccharides and infant gut microbiota, Sci. Rep. 7 (2017) 40466. https://doi.org/10.1038/srep40466.
T. Matsuki, K. Yahagi, H. Mori, et al., A key genetic factor for fucosyllactose utilization affects infant gut microbiota development, Nat. Commun. 7 (2016) 11939. https://doi.org/10.1038/ncomms11939.
B. Berger, N. Porta, F. Foata, et al., Linking human milk oligosaccharides, infant fecal community types, and later risk to require antibiotics, mBio 11(2) (2020) e03196-19. https://doi.org/10.1128/mBio.03196-19.
L. Bode, E. Jantscher-Krenn, Structure-function relationships of human milk oligosaccharides, Adv. Nutr. 3(3) (2012) 383s–391s. https://doi.org/10.3945/an.111.001404.
P. K. Berger, J. F. Plows, R. B. Jones, et al., Human milk oligosaccharide 2’-fucosyllactose links feedings at 1 month to cognitive development at 24 months in infants of normal and overweight mothers, PLoS ONE 15(2) (2020) e0228323. https://doi.org/10.1371/journal.pone.0228323.
S. Rudloff, S. Kuntz, S. O. Rasmussen, et al., Metabolism of milk oligosaccharides in preterm pigs sensitive to necrotizing enterocolitis, Front. Nutr. 6(23) (2019) 23. https://doi.org/10.3389/fnut.2019.00023.
B. Wang, B. Yu, M. Karim, et al., Dietary sialic acid supplementation improves learning and memory in piglets, Am. J. Clin. Nutr. 85(2) (2007) 561–569. https://doi.org/10.1093/ajcn/85.2.561.
C. P. Sodhi, P. Wipf, Y. Yamaguchi, et al., The human milk oligosaccharides 2’-fucosyllactose and 6’-sialyllactose protect against the development of necrotizing enterocolitis by inhibiting toll-like receptor 4 signaling, Pediatr. Res. 89(1) (2021) 91–101. https://doi.org/10.1038/s41390-020-0852-3.
A. Marcobal, M. Barboza, E. D. Sonnenburg, et al., Bacteroides in the infant gut consume milk oligosaccharides via mucus-utilization pathways, Cell Host Microbe. 10(5) (2011) 507–514. https://doi.org/10.1016/j.chom.2011.10.007.
L. Xiao, B. Van’t Land, P. A. Engen, et al., Human milk oligosaccharides protect against the development of autoimmune diabetes in NOD-mice, Sci. Rep. 8 (2018) 3829. https://doi.org/10.1038/s41598-018-22052-y.
L. Xiao, T. Leusink-Muis, N. Kettelarij, et al., Human milk oligosaccharide 2’-fucosyllactose improves innate and adaptive immunity in an influenza-specific murine vaccination model, Front. Immunol. 9 (2018) 452. https://doi.org/10.3389/fimmu.2018.00452.
L. Castillo-Courtade, S. Han, S. Lee, et al., Attenuation of food allergy symptoms following treatment with human milk oligosaccharides in a mouse model, Allergy 70(9) (2015) 1091–1102. https://doi.org/10.1111/all.12650.
M. Good, C. P. Sodhi, Y. Yamaguchi, et al., The human milk oligosaccharide 2’-fucosyllactose attenuates the severity of experimental necrotising enterocolitis by enhancing mesenteric perfusion in the neonatal intestine, Brit. J. Nutr. 116(7) (2016) 1175–1187. https://doi.org/10.1017/S0007114516002944.
R. Y. Wu, B. Li, Y. Koike, et al., Human milk oligosaccharides increase mucin expression in experimental necrotizing enterocolitis, Mol. Nutr. Food Res. 63(3) (2019) e1800658. https://doi.org/10.1002/mnfr.201800658.
E. Jantscher-Krenn, M. Zherebtsov, C. Nissan, et al., The human milk oligosaccharide disialyllacto- N-tetraose prevents necrotising enterocolitis in neonatal rats, Gut 61(10) (2012) 1417–1425. https://doi.org/10.1136/gutjnl-2011-301404.
C. A. Autran, M. H. C. Schoterman, E. Jantscher-Krenn, et al., Sialylated galacto-oligosaccharides and 2’-fucosyllactose reduce necrotising enterocolitis in neonatal rats, Brit. J. Nutr. 116(2) (2016) 294–299. https://doi.org/10.1017/S0007114516002038.
E. Vazquez, A. Barranco, M. Ramirez, et al., Dietary 2’-fucosyllactose enhances operant conditioning and long-term potentiation via gut-brain communication through the vagus nerve in rodents, PLoS ONE 11(11) (2016) e0166070. https://doi.org/10.1371/journal.pone.0166070.
F. Chleilat, T. Klancic, K. Ma, et al., Human milk oligosaccharide supplementation affects intestinal barrier function and microbial composition in the gastrointestinal tract of young sprague dawley rats, Nutrients 12(5) (2020) 1532. https://doi.org/10.3390/nu12051532.
D. W. Kavanaugh, J. O’Callaghan, L. F. Butto, et al., Exposure of Bifidobacterium longum subsp. infantis to milk oligosaccharides increases adhesion to epithelial cells and induces a substantial transcriptional response, PLoS ONE 8(6) (2013) e67224. https://doi.org/10.1371/journal.pone.0067224.
H. D. Holscher, L. Bode, K. A. Tappenden, Human milk oligosaccharides influence intestinal epithelial cell maturation in vitro, J. Pediatr. Gastr. Nutr. 64(2) (2017) 296–301. https://doi.org/10.1097/Mpg.0000000000001274.
C. L. Kong, M. Elderman, L. H. Cheng, et al., Modulation of intestinal epithelial glycocalyx development by human milk oligosaccharides and non-digestible carbohydrates, Mol. Nutr. Food Res. 63(17) (2019) e1900303. https://doi.org/10.1002/mnfr.201900303.
L. H. Cheng, C. L. Kong, M. T. C. Walvoort, et al., Human milk oligosaccharides differently modulate goblet cells under homeostatic, proinflammatory conditions and ER stress, Mol. Nutr. Food Res. 64(5) (2020) e1900976. https://doi.org/10.1002/mnfr.201900976.
T. Eiwegger, B. Stahl, P. Haidl, et al., Prebiotic oligosaccharides: in vitro evidence for gastrointestinal epithelial transfer and immunomodulatory properties, Pediatr. Allergy Immunol. 21(8) (2010) 1179–1188. https://doi.org/10.1111/j.1399-3038.2010.01062.x.
V. Ayechu-Muruzabal, S. A. Overbeek, A. I. Kostadinova, et al., Exposure of intestinal epithelial cells to 2’-fucosyllactose and CpG enhances galectin release and instructs dendritic cells to drive Th1 and regulatory-type immune development, Biomolecules 10(5) (2020) 784. https://doi.org/10.3390/biom10050784.
J. Le Pendu, Histo-blood group antigen and human milk oligosaccharides: genetic polymorphism and risk of infectious diseases, Prot. Infants Hum. Milk. 554 (2004) 135–143.
Z. T. Yu, N. N. Nanthakumar, D. S. Newburg, The human milk oligosaccharide 2’-fucosyllactose quenches Campylobacter jejuni-induced inflammation in human epithelial cells HEp-2 and HT-29 and in mouse intestinal mucosa, J. Nutr. 146(10) (2016) 1980–1990. https://doi.org/10.3945/jn.116.230706.
G. V. Coppa, L. Zampini, T. Galeazzi, et al., Human milk oligosaccharides inhibit the adhesion to Caco-2 cells of diarrheal pathogens: Escherichia coli, Vibrio cholerae, and Salmonella fyris, Pediatr. Res. 59(3) (2006) 377–382. https://doi.org/10.1203/01.pdr.0000200805.45593.17.
J. V. Mysore, T. Wigginton, P. M. Simon, et al., Treatment of Helicobacter pylori infection in rhesus monkeys using a novel antiadhesion compound, Gastroenterology 117(6) (1999) 1316–1325. https://doi.org/10.1016/S0016-5085(99)70282-9.
P. Hong, M. R. Ninonuevo, B. Lee, et al., Human milk oligosaccharides reduce HIV-1-gp120 binding to dendritic cell-specific ICAM3-grabbing non-integrin (DC-SIGN), Brit. J. Nutr. 101(4) (2009) 482–486. https://doi.org/10.1017/S0007114508025804.
J. Shang, V. E. Piskarev, M. Xia, et al., Identifying human milk glycans that inhibit norovirus binding using surface plasmon resonance, Glycobiology 23(12) (2013) 1491–1498. https://doi.org/10.1093/glycob/cwt077.
J. M. Choi, A. M. Hutson, M. K. Estes, et al., Atomic resolution structural characterization of recognition of histo-blood group antigens by Norwalk virus, PNAS 105(27) (2008) 9175–9180. https://doi.org/10.1073/pnas.0803275105.
L. Y. Hu, S. Ramani, R. Czako, et al., Structural basis of glycan specificity in neonate-specific bovine-human reassortant rotavirus, Nat. Commun. 6 (2015) 8346. https://doi.org/10.1038/ncomms9346.
D. J. Ashline, Y. Yu, Y. Lasanajak, et al., Structural characterization by multistage mass spectrometry (MS n ) of human milk glycans recognized by human rotaviruses, Mol. Cell. Proteomics 13(11) (2014) 2961–2974. https://doi.org/10.1074/mcp.M114.039925.
S. Zevgiti, J. G. Zabala, A. Darji, et al., Sialic acid and sialyl-lactose glyco-conjugates: design, synthesis and binding assays to lectins and swine influenza H1N1 virus, J. Pept. Sci. 18(1) (2012) 52–58. https://doi.org/10.1002/psc.1415.
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