1932

Abstract

The intestinal barrier is essential in early life to prevent infection, inflammation, and food allergies. It consists of microbiota, a mucus layer, an epithelial layer, and the immune system. Microbial metabolites, the mucus, antimicrobial peptides, and secretory immunoglobulin A (sIgA) protect the intestinal mucosa against infection. The complex interplay between these functionalities of the intestinal barrier is crucial in early life by supporting homeostasis, development of the intestinal immune system, and long-term gut health. Exclusive breastfeeding is highly recommended during the first 6 months. When breastfeeding is not possible, milk-based infant formulas are a safe alternative. Breast milk contains many bioactive components that help to establish the intestinal microbiota and influence the development of the intestinal epithelium and the immune system. Importantly, breastfeeding lowers the risk for intestinal and respiratory tract infections. Here we review all aspects of intestinal barrier function and the nutritional components that impact its functionality in early life, such asmicronutrients, bioactive milk proteins, milk lipids, and human milk oligosaccharides. These components are present in breast milk and can be added to milk-based infant formulas to support gut health and immunity.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-nutr-122221-103916
2022-08-22
2024-10-04
Loading full text...

Full text loading...

/deliver/fulltext/nutr/42/1/annurev-nutr-122221-103916.html?itemId=/content/journals/10.1146/annurev-nutr-122221-103916&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Aarts J, Boleij A, Pieters BCH, Feitsma AL, van Neerven RJJ et al. 2021. Flood control: how milk-derived extracellular vesicles can help to improve the intestinal barrier function and break the gut-joint axis in rheumatoid arthritis. Front. Immunol. 12:703277
    [Google Scholar]
  2. 2.
    Abbring S, Hols G, Garssen J, van Esch BCAM. 2019. Raw cow's milk consumption and allergic diseases: the potential role of bioactive whey proteins. Eur. J. Pharmacol. 843:55–65
    [Google Scholar]
  3. 3.
    Abbring S, Ryan JT, Diks MAP, Hols G, Garssen J, van Esch BCAM. 2019. Suppression of food allergic symptoms by raw cow's milk in mice is retained after skimming but abolished after heating the milk—a promising contribution of alkaline phosphatase. Nutrients 11:71499
    [Google Scholar]
  4. 4.
    Actor JK, Hwang S-A, Kruzel ML. 2009. Lactoferrin as a natural immune modulator. Curr. Pharm. Des. 15:171956–73
    [Google Scholar]
  5. 5.
    Admyre C, Johansson SM, Qazi KR, Filen JJ, Lahesmaa R et al. 2007. Exosomes with immune modulatory features are present in human breast milk. J. Immunol. 179:31969–78
    [Google Scholar]
  6. 6.
    Agin M, Yucel A, Gumus M, Yuksekkaya HA, Tumgor G. 2019. The effect of enteral nutrition support rich in TGF-β in the treatment of inflammatory bowel disease in childhood. Medicina 55:10620
    [Google Scholar]
  7. 7.
    Akbari P, Braber S, Alizadeh A, Verheijden KAT, Schoterman MHC et al. 2015. Galacto-oligosaccharides protect the intestinal barrier by maintaining the tight junction network and modulating the inflammatory responses after a challenge with the mycotoxin deoxynivalenol in human Caco-2 cell monolayers and B6C3F1 mice. J. Nutr. 145:71604–13
    [Google Scholar]
  8. 8.
    Ambros V 2004. The functions of animal microRNAs. Nature 431:7006350–55
    [Google Scholar]
  9. 9.
    Andreas NJ, Kampmann B, Mehring Le-Doare K. 2015. Human breast milk: a review on its composition and bioactivity. Early Hum. Dev. 91:11629–35
    [Google Scholar]
  10. 10.
    Apetoh L, Quintana FJ, Pot C, Joller N, Xiao S et al. 2010. The aryl hydrocarbon receptor interacts with c-Maf to promote the differentiation of type 1 regulatory T cells induced by IL-27. Nat. Immunol. 11:9854–61
    [Google Scholar]
  11. 11.
    Arrieta M-C, Stiemsma LT, Amenyogbe N, Brown EM, Finlay B. 2014. The intestinal microbiome in early life: health and disease. Front. Immunol. 5:427
    [Google Scholar]
  12. 12.
    Arslanoglu S, Moro GE, Boehm G. 2007. Early supplementation of prebiotic oligosaccharides protects formula-fed infants against infections during the first 6 months of life. J. Nutr. 137:112420–24
    [Google Scholar]
  13. 13.
    Asmuth DM, Ma Z-M, Albanese A, Sandler NG, Devaraj S et al. 2013. Oral serum-derived bovine immunoglobulin improves duodenal immune reconstitution and absorption function in patients with HIV enteropathy. AIDS 27:142207–17
    [Google Scholar]
  14. 14.
    Atarashi K, Tanoue T, Ando M, Kamada N, Nagano Y et al. 2015. Th17 cell induction by adhesion of microbes to intestinal epithelial cells. Cell 163:2367–80
    [Google Scholar]
  15. 15.
    Atarashi K, Tanoue T, Oshima K, Suda W, Nagano Y et al. 2013. Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature 500:7461232–36
    [Google Scholar]
  16. 16.
    Autran CA, Schoterman MHC, Jantscher-Krenn E, Kamerling JP, Bode L. 2016. Sialylated galacto-oligosaccharides and 2′-fucosyllactose reduce necrotising enterocolitis in neonatal rats. Br. J. Nutr. 116:2294–99
    [Google Scholar]
  17. 17.
    Bakker-Zierikzee AM, Tol EAF, Kroes H, Alles MS, Kok FJ, Bindels JG. 2006. Faecal SIgA secretion in infants fed on pre- or probiotic infant formula. Pediatr. Allergy Immunol. 17:2134–40
    [Google Scholar]
  18. 18.
    Barnard JA, Beauchamp RD, Coffey RJ, Moses HL. 1989. Regulation of intestinal epithelial cell growth by transforming growth factor type β. PNAS 86:51578–82
    [Google Scholar]
  19. 19.
    Bateman E, Weaver E, Klein G, Wignall A, Wozniak B et al. 2016. Serum-derived bovine immunoglobulin/protein isolate in the alleviation of chemotherapy-induced mucositis. Support. Care Cancer 24:1377–85
    [Google Scholar]
  20. 20.
    Bates JM, Akerlund J, Mittge E, Guillemin K. 2007. Intestinal alkaline phosphatase detoxifies lipopolysaccharide and prevents inflammation in zebrafish in response to the gut microbiota. Cell Host Microbe 2:6371–82
    [Google Scholar]
  21. 21.
    Bayram RO, Özdemir H, Emsen A, Türk Dağı H, Artaç H 2019. Reference ranges for serum immunoglobulin (IgG, IgA, and IgM) and IgG subclass levels in healthy children. Turk. . J. Med. Sci. 49:2497–505
    [Google Scholar]
  22. 22.
    Beguin P, Errachid A, Larondelle Y, Schneider Y-J. 2013. Effect of polyunsaturated fatty acids on tight junctions in a model of the human intestinal epithelium under normal and inflammatory conditions. Food Funct 4:6923–31
    [Google Scholar]
  23. 23.
    Ben XM, Zhou XY, Zhao WH, Yu WL, Pan W et al. 2004. Supplementation of milk formula with galacto-oligosaccharides improves intestinal micro-flora and fermentation in term infants. Chin. Med. J. 117:6927–31
    [Google Scholar]
  24. 24.
    Bender B, Baranyi M, Kerekes A, Bodrogi L, Brands R et al. 2015. Recombinant human tissue non-specific alkaline phosphatase successfully counteracts lipopolysaccharide induced sepsis in mice. Physiol. Res. 64:5731–38
    [Google Scholar]
  25. 25.
    Benmoussa A, Diallo I, Salem M, Michel S, Gilbert C et al. 2019. Concentrates of two subsets of extracellular vesicles from cow's milk modulate symptoms and inflammation in experimental colitis. Sci. Rep. 9:114661
    [Google Scholar]
  26. 26.
    Benmoussa A, Lee CHC, Laffont B, Savard P, Laugier J et al. 2016. Commercial dairy cow milk microRNAs resist digestion under simulated gastrointestinal tract conditions. J. Nutr. 146:112206–15
    [Google Scholar]
  27. 27.
    Betker JL, Angle BM, Graner MW, Anchordoquy TJ. 2019. The potential of exosomes from cow milk for oral delivery. J. Pharm. Sci. 108:41496–505
    [Google Scholar]
  28. 28.
    Beumer C, Wulferink M, Raaben W, Fiechter D, Brands R, Seinen W. 2003. Calf intestinal alkaline phosphatase, a novel therapeutic drug for lipopolysaccharide (LPS)-mediated diseases, attenuates LPS toxicity in mice and piglets. J. Pharmacol. Exp. Ther. 307:2737–44
    [Google Scholar]
  29. 29.
    Bhatia S, Prabhu PN, Benefiel AC, Miller MJ, Chow J et al. 2015. Galacto-oligosaccharides may directly enhance intestinal barrier function through the modulation of goblet cells. Mol. Nutr. Food Res. 59:3566–73
    [Google Scholar]
  30. 30.
    Bhinder G, Allaire JM, Garcia C, Lau JT, Chan JM et al. 2017. Milk fat globule membrane supplementation in formula modulates the neonatal gut microbiome and normalizes intestinal development. Sci. Rep. 7:145274
    [Google Scholar]
  31. 31.
    Bibel DJ, Aly R, Shinefield HR. 1992. Inhibition of microbial adherence by sphinganine. Can. J. Microbiol. 38:9983–85
    [Google Scholar]
  32. 32.
    Bischoff SC. 2011.. “ Gut health”: a new objective in medicine?. BMC Med 9:24
    [Google Scholar]
  33. 33.
    Bischoff SC, Barbara G, Buurman W, Ockhuizen T, Schulzke J-D et al. 2014. Intestinal permeability: a new target for disease prevention and therapy. BMC Gastroenterol 14:1189
    [Google Scholar]
  34. 34.
    Bodammer P, Kerkhoff C, Maletzki C, Lamprecht G. 2013. Bovine colostrum increases pore-forming claudin-2 protein expression but paradoxically not ion permeability possibly by a change of the intestinal cytokine milieu. PLOS ONE 8:5e64210
    [Google Scholar]
  35. 35.
    Bode L. 2006. Recent advances on structure, metabolism, and function of human milk oligosaccharides. J. Nutr. 136:82127–30
    [Google Scholar]
  36. 36.
    Bode L. 2012. Human milk oligosaccharides: Every baby needs a sugar mama. Glycobiology 22:91147–62
    [Google Scholar]
  37. 37.
    Bovee-Oudenhoven IMJ, Lettink-Wissink MLG, Van Doesburg W, Witteman BJM, van der Meer R. 2003. Diarrhea caused by enterotoxigenic Escherichia coli infection of humans is inhibited by dietary calcium. Gastroenterology 125:2469–76
    [Google Scholar]
  38. 38.
    Brambell FW. 1966. The transmission of immunity from mother to young and the catabolism of immunoglobulins. Lancet 2:74731087–93
    [Google Scholar]
  39. 39.
    Brick T, Hettinga K, Kirchner B, Pfaffl MW, Ege MJ. 2020. The beneficial effect of farm milk consumption on asthma, allergies, and infections: from meta-analysis of evidence to clinical trial. J. Allergy Clin. Immunol. Pract. 8:3878–89.e3
    [Google Scholar]
  40. 40.
    Bron PA, Kleerebezem M, Brummer R-J, Cani PD, Mercenier A et al. 2017. Can probiotics modulate human disease by impacting intestinal barrier function?. Br. J. Nutr. 117:193–107
    [Google Scholar]
  41. 41.
    Brown AJ, Goldsworthy SM, Barnes AA, Eilert MM, Tcheang L et al. 2003. The orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J. Biol. Chem. 278:1311312–19
    [Google Scholar]
  42. 42.
    Brugman S, Perdijk O, van Neerven RJJ, Savelkoul HFJ. 2015. Mucosal immune development in early life: setting the stage. Arch. Immunol. Ther. Exp. 63:4251–68
    [Google Scholar]
  43. 43.
    Bruzzese E, Volpicelli M, Squeglia V, Bruzzese D, Salvini F et al. 2009. A formula containing galacto- and fructo-oligosaccharides prevents intestinal and extra-intestinal infections: an observational study. Clin Nutr 28:2156–61
    [Google Scholar]
  44. 44.
    Buccigrossi V, de Marco G, Bruzzese E, Ombrato L, Bracale I et al. 2007. Lactoferrin induces concentration-dependent functional modulation of intestinal proliferation and differentiation. Pediatr. Res. 61:4410–14
    [Google Scholar]
  45. 45.
    Buisine MP, Devisme L, Savidge TC, Gespach C, Gosselin B et al. 1998. Mucin gene expression in human embryonic and fetal intestine. Gut 43:4519–24
    [Google Scholar]
  46. 46.
    Campeotto F, Baldassarre M, Laforgia N, Viallon V, Kalach N et al. 2010. Fecal expression of human β-defensin-2 following birth. Neonatology 98:4365–69
    [Google Scholar]
  47. 47.
    Cantorna MT, Snyder L, Arora J. 2019. Vitamin A and vitamin D regulate the microbial complexity, barrier function, and the mucosal immune responses to ensure intestinal homeostasis. Crit. Rev. Biochem. Mol. Biol. 54:2184–92
    [Google Scholar]
  48. 48.
    Castillo-Courtade L, Han S, Lee S, Mian FM, Buck R, Forsythe P. 2015. Attenuation of food allergy symptoms following treatment with human milk oligosaccharides in a mouse model. Allergy 70:91091–102
    [Google Scholar]
  49. 49.
    Castro-Bravo N, Margolles A, Wells JM, Ruas-Madiedo P. 2019. Exopolysaccharides synthesized by Bifidobacterium animalis subsp. lactis interact with TLR4 in intestinal epithelial cells. Anaerobe 56:98–101
    [Google Scholar]
  50. 50.
    Castro-Bravo N, Wells JM, Margolles A, Ruas-Madiedo P. 2018. Interactions of surface exopolysaccharides from Bifidobacterium and Lactobacillus within the intestinal environment. Front. Microbiol. 9:2426
    [Google Scholar]
  51. 51.
    Catassi C, Bonucci A, Coppa GV, Carlucci A, Giorgi PL. 1995. Intestinal permeability changes during the first month: effect of natural versus artificial feeding. J. Pediatr. Gastroenterol. Nutr. 21:4383–86
    [Google Scholar]
  52. 52.
    Chang H-Y, Chen J-H, Chang J-H, Lin H-C, Lin C-Y, Peng C-C. 2017. Multiple strains probiotics appear to be the most effective probiotics in the prevention of necrotizing enterocolitis and mortality: an updated meta-analysis. PLOS ONE 12:2e0171579
    [Google Scholar]
  53. 53.
    Chatchatee P, Lee WS, Carrilho E, Kosuwon P, Simakachorn N et al. 2014. Effects of growing-up milk supplemented with prebiotics and LCPUFAs on infections in young children. J. Pediatr. Gastroenterol. Nutr. 58:4428–37
    [Google Scholar]
  54. 54.
    Chatterton DEW, Nguyen DN, Bering SB, Sangild PT. 2013. Anti-inflammatory mechanisms of bioactive milk proteins in the intestine of newborns. Int. J. Biochem. Cell Biol. 45:81730–47
    [Google Scholar]
  55. 55.
    Chen B, Chen H, Shu X, Yin Y, Li J et al. 2018. Presence of segmented filamentous bacteria in human children and its potential role in the modulation of human gut immunity. Front. Microbiol. 9:1403
    [Google Scholar]
  56. 56.
    Chen KT, Malo MS, Beasley-Topliffe LK, Poelstra K, Millan JL et al. 2011. A role for intestinal alkaline phosphatase in the maintenance of local gut immunity. Dig. Dis. Sci. 56:41020–27
    [Google Scholar]
  57. 57.
    Chen S-W, Ma Y-Y, Zhu J, Zuo S, Zhang J-L et al. 2015. Protective effect of 1,25-dihydroxyvitamin D3 on ethanol-induced intestinal barrier injury both in vitro and in vivo. Toxicol. Lett. 237:279–88
    [Google Scholar]
  58. 58.
    Chen T, Xie M-Y, Sun J-J, Ye R-S, Cheng X et al. 2016. Porcine milk–derived exosomes promote proliferation of intestinal epithelial cells. Sci. Rep. 6:33862
    [Google Scholar]
  59. 59.
    Cuello-Garcia CA, Brozek JL, Fiocchi A, Pawankar R, Yepes-Nunez JJ et al. 2015. Probiotics for the prevention of allergy: a systematic review and meta-analysis of randomized controlled trials. J. Allergy Clin. Immunol. 136:4952–61
    [Google Scholar]
  60. 60.
    Cummings JH, Antoine J-M, Azpiroz F, Bourdet-Sicard R, Brandtzaeg P et al. 2004. PASSCLAIM—gut health and immunity. Eur. J. Nutr. 43:Suppl. 2II118–73
    [Google Scholar]
  61. 61.
    Davidson LA, Lönnerdal B. 1987. Persistence of human milk proteins in the breast-fed infant. Acta Paediatr. Scand. 76:5733–40
    [Google Scholar]
  62. 62.
    de Medeiros PHQS, Pinto DV, de Almeida JZ, Rêgo JMC, Rodrigues FAP et al. 2018. Modulation of intestinal immune and barrier functions by vitamin A: implications for current understanding of malnutrition and enteric infections in children. Nutrients 10:91128
    [Google Scholar]
  63. 63.
    Denno DM, VanBuskirk K, Nelson ZC, Musser CA, Hay Burgess DC, Tarr PI 2014. Use of the lactulose to mannitol ratio to evaluate childhood environmental enteric dysfunction: a systematic review. Clin. Infect. Dis. 59:Suppl. 4S213–19
    [Google Scholar]
  64. 64.
    Derrien M, Collado MC, Ben-Amor K, Salminen S, de Vos WM. 2008. The mucin degrader Akkermansia muciniphila is an abundant resident of the human intestinal tract. Appl. Environ. Microbiol. 74:51646–48
    [Google Scholar]
  65. 65.
    Detzel CJ, Horgan A, Henderson AL, Petschow BW, Warner CD et al. 2015. Bovine immunoglobulin/protein isolate binds pro-inflammatory bacterial compounds and prevents immune activation in an intestinal co-culture model. PLOS ONE 10:4e0120278
    [Google Scholar]
  66. 66.
    Dimitrov V, White JH. 2017. Vitamin D signaling in intestinal innate immunity and homeostasis. Mol. Cell. Endocrinol. 453:68–78
    [Google Scholar]
  67. 67.
    Dominguez-Bello MG, De Jesus–Laboy KM, Shen N, Cox LM, Amir A et al. 2016. Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer. Nat. Med. 22:3250–53
    [Google Scholar]
  68. 68.
    Ducarmon QR, Zwittink RD, Hornung BVH, van Schaik W, Young VB, Kuijper EJ. 2019. Gut microbiota and colonization resistance against bacterial enteric infection. Microbiol. Mol. Biol. Rev. 83:3e00007–19
    [Google Scholar]
  69. 69.
    Duijts L, Jaddoe VWV, Hofman A, Moll HA. 2010. Prolonged and exclusive breastfeeding reduces the risk of infectious diseases in infancy. Pediatrics 126:1e18–25
    [Google Scholar]
  70. 70.
    Durkin LA, Childs CE, Calder PC. 2021. Omega-3 polyunsaturated fatty acids and the intestinal epithelium—a review. Foods 10:1199
    [Google Scholar]
  71. 71.
    EFSA Panel Diet. Prod. Nutr. Allerg 2014. Scientific opinion on the essential composition of infant and follow-on formulae. EFSA J. 12:3760
    [Google Scholar]
  72. 72.
    Ehrlich AM, Pacheco AR, Henrick BM, Taft D, Xu G et al. 2020. Indole-3-lactic acid associated with Bifidobacterium-dominated microbiota significantly decreases inflammation in intestinal epithelial cells. BMC Microbiol 20:1357
    [Google Scholar]
  73. 73.
    Elizondo G, Rodríguez-Sosa M, Estrada-Muñiz E, Gonzalez FJ, Vega L. 2011. Deletion of the aryl hydrocarbon receptor enhances the inflammatory response to Leishmania major infection. Int. J. Biol. Sci. 7:91220–29
    [Google Scholar]
  74. 74.
    Estorninos E, Lawenko RB, Palestroque E, Sprenger N, Benyacoub J et al. 2022. Term infant formula supplemented with milk-derived oligosaccharides shifts the gut microbiota closer to that of human milk–fed infants and improves intestinal immune defense: a randomized controlled trial. Am. J. Clin. Nutr. 115:142–53
    [Google Scholar]
  75. 75.
    FAO (Food Agric. Organ.)/WHO (World Health Organ.) 2020. Standard for infant formula and formulas for special medical purposes intended for infants Codex Stand. 72-1981 FAO/WHO
    [Google Scholar]
  76. 76.
    Fehr K, Moossavi S, Sbihi H, Boutin RCT, Bode L et al. 2020. Breastmilk feeding practices are associated with the co-occurrence of bacteria in mothers’ milk and the infant gut: the CHILD Cohort Study. Cell Host Microbe 28:2285–97.e4
    [Google Scholar]
  77. 77.
    Fell JM, Paintin M, Arnaud-Battandier F, Beattie RM, Hollis A et al. 2000. Mucosal healing and a fall in mucosal pro-inflammatory cytokine mRNA induced by a specific oral polymeric diet in paediatric Crohn's disease. Aliment. Pharmacol. Ther. 14:3281–89
    [Google Scholar]
  78. 78.
    Florén C-H, Chinenye S, Elfstrand L, Hagman C, Ihse I et al. 2006. ColoPlus, a new product based on bovine colostrum, alleviates HIV-associated diarrhoea. Scand. J. Gastroenterol. 41:6682–86
    [Google Scholar]
  79. 79.
    Fuller KL, Kuhlenschmidt TB, Kuhlenschmidt MS, Jiménez-Flores R, Donovan SM. 2013. Milk fat globule membrane isolated from buttermilk or whey cream and their lipid components inhibit infectivity of rotavirus in vitro. J. Dairy Sci. 96:63488–97
    [Google Scholar]
  80. 80.
    Funatake CJ, Ao K, Suzuki T, Murai H, Yamamoto M et al. 2009. Expression of constitutively-active aryl hydrocarbon receptor in T-cells enhances the down-regulation of CD62L, but does not alter expression of CD25 or suppress the allogeneic CTL response. J. Immunotoxicol. 6:3194–203
    [Google Scholar]
  81. 81.
    Gandhi R, Kumar D, Burns EJ, Nadeau M, Dake B et al. 2010. Activation of the aryl hydrocarbon receptor induces human type 1 regulatory T cell–like and Foxp3+ regulatory T cells. Nat. Immunol. 11:9846–53
    [Google Scholar]
  82. 82.
    Gao R, Zhang R, Qian T, Peng X, He W et al. 2019. A comparison of exosomes derived from different periods breast milk on protecting against intestinal organoid injury. Pediatr. Surg. Int. 35:121363–68
    [Google Scholar]
  83. 83.
    Gao Y, Hou L, Lu C, Wang Q, Pan B et al. 2020. Enteral lactoferrin supplementation for preventing sepsis and necrotizing enterocolitis in preterm infants: a meta-analysis with trial sequential analysis of randomized controlled trials. Front. Pharmacol. 11:1186
    [Google Scholar]
  84. 84.
    García-Montoya IA, Cendón TS, Arévalo-Gallegos S, Rascón-Cruz Q. 2012. Lactoferrin a multiple bioactive protein: an overview. Biochim. Biophys. Acta 1820:3226–36
    [Google Scholar]
  85. 85.
    Gauthier S, Pouliot Y, Maubois J. 2006. Growth factors from bovine milk and colostrum: composition, extraction and biological activities. Lait 86:299–125
    [Google Scholar]
  86. 86.
    Gbylik-Sikorska M, Gajda A, Burmańczuk A, Grabowski T, Posyniak A. 2019. Development of a UHPLC-MS/MS method for the determination of quercetin in milk and its application to a pharmacokinetic study. J. Vet. Res. 63:187–91
    [Google Scholar]
  87. 87.
    German JB, Freeman SL, Lebrilla CB, Mills DA. 2008. Human milk oligosaccharides: evolution, structures and bioselectivity as substrates for intestinal bacteria. Nestle Nutr. Workshop Ser. Pediatr. Prog. 62:205–18
    [Google Scholar]
  88. 88.
    Gilbert MS, Ijssennagger N, Kies AK, van Mil SWC. 2018. Protein fermentation in the gut; implications for intestinal dysfunction in humans, pigs, and poultry. Am. J. Physiol. Gastrointest. Liver Physiol. 315:2G159–70
    [Google Scholar]
  89. 89.
    Gomez de Agüero M, Ganal-Vonarburg S, Fuhrer T, Rupp S, Uchimura Y et al. 2016. The maternal microbiota drives early postnatal innate immune development. Science 351:62791296–302
    [Google Scholar]
  90. 90.
    Good M, Sodhi CP, Yamaguchi Y, Jia H, Lu P et al. 2016. The human milk oligosaccharide 2′-fucosyllactose attenuates the severity of experimental necrotising enterocolitis by enhancing mesenteric perfusion in the neonatal intestine. Br. J. Nutr. 116:71175–87
    [Google Scholar]
  91. 91.
    Goto Y, Uematsu S, Kiyono H. 2016. Epithelial glycosylation in gut homeostasis and inflammation. Nat. Immunol. 17:111244–51
    [Google Scholar]
  92. 92.
    Granger CL, Embleton ND, Palmer JM, Lamb CA, Berrington JE, Stewart CJ. 2021. Maternal breastmilk, infant gut microbiome and the impact on preterm infant health. Acta Paediatr 110:2450–57
    [Google Scholar]
  93. 93.
    Guzman-Prado Y, Samson O, Segal JP, Limdi JK, Hayee B. 2020. Vitamin D therapy in adults with inflammatory bowel disease: a systematic review and meta-analysis. Inflamm. Bowel Dis. 26:121819–30
    [Google Scholar]
  94. 94.
    Hagiwara T, Shinoda I, Fukuwatari Y, Shimamura S. 1995. Effects of lactoferrin and its peptides on proliferation of rat intestinal epithelial cell line, IEC-18, in the presence of epidermal growth factor. Biosci. Biotechnol. Biochem. 59:101875–81
    [Google Scholar]
  95. 95.
    Hancock JT, Salisbury V, Ovejero-Boglione MC, Cherry R, Hoare C et al. 2002. Antimicrobial properties of milk: dependence on presence of xanthine oxidase and nitrite. Antimicrob. Agents Chemother. 46:103308–10
    [Google Scholar]
  96. 96.
    He C, Deng J, Hu X, Zhou S, Wu J et al. 2019. Vitamin A inhibits the action of LPS on the intestinal epithelial barrier function and tight junction proteins. Food Funct 10:21235–42
    [Google Scholar]
  97. 97.
    He L, Liu T, Shi Y, Tian F, Hu H et al. 2018. Gut epithelial vitamin D receptor regulates microbiota-dependent mucosal inflammation by suppressing intestinal epithelial cell apoptosis. Endocrinology 159:2967–79
    [Google Scholar]
  98. 98.
    He Y, Liu S, Kling DE, Leone S, Lawlor NT et al. 2016. The human milk oligosaccharide 2′-fucosyllactose modulates CD14 expression in human enterocytes, thereby attenuating LPS-induced inflammation. Gut 65:133–46
    [Google Scholar]
  99. 99.
    van der Hee B, Wells JM. 2021. Microbial regulation of host physiology by short-chain fatty acids. Trends Microbiol 29:8700–12
    [Google Scholar]
  100. 100.
    Hegyi P, Maléth J, Walters JR, Hofmann AF, Keely SJ. 2018. Guts and gall: bile acids in regulation of intestinal epithelial function in health and disease. Physiol. Rev. 98:41983–2023
    [Google Scholar]
  101. 101.
    Henderson AL, Brand MW, Darling RJ, Maas KJ, Detzel CJ et al. 2015. Attenuation of colitis by serum-derived bovine immunoglobulin/protein isolate in a defined microbiota mouse model. Dig. Dis. Sci. 60:113293–303
    [Google Scholar]
  102. 102.
    Hering NA, Luettig J, Krug SM, Wiegand S, Gross G et al. 2017. Lactoferrin protects against intestinal inflammation and bacteria-induced barrier dysfunction in vitro. Ann. N. Y. Acad. Sci. 1405:1177–88
    [Google Scholar]
  103. 103.
    Hiippala K, Jouhten H, Ronkainen A, Hartikainen A, Kainulainen V et al. 2018. The potential of gut commensals in reinforcing intestinal barrier function and alleviating inflammation. Nutrients 10:8988
    [Google Scholar]
  104. 104.
    Holscher HD, Davis SR, Tappenden KA. 2014. Human milk oligosaccharides influence maturation of human intestinal Caco-2Bbe and HT-29 cell lines. J. Nutr. 144:5586–91
    [Google Scholar]
  105. 105.
    Holvoet S, Perrot M, de Groot N, Prioult G, Mikogami T et al. 2019. Oral tolerance induction to newly introduced allergen is favored by a transforming growth factor-β-enriched formula. Nutrients 11:92210
    [Google Scholar]
  106. 106.
    Hosono A, Ozawa A, Kato R, Ohnishi Y, Nakanishi Y et al. 2003. Dietary fructooligosaccharides induce immunoregulation of intestinal IgA secretion by murine Peyer's patch cells. Biosci. Biotechnol. Biochem. 67:4758–64
    [Google Scholar]
  107. 107.
    Hu P, Zhao F, Zhu W, Wang J. 2019. Effects of early-life lactoferrin intervention on growth performance, small intestinal function and gut microbiota in suckling piglets. Food Funct 10:95361–73
    [Google Scholar]
  108. 108.
    Huang XH, Chen L, Gao W, Zhang W, Chen SJ et al. 2008. Specific IgG activity of bovine immune milk against diarrhea bacteria and its protective effects on pathogen-infected intestinal damages. Vaccine 26:475973–80
    [Google Scholar]
  109. 109.
    Ivanov II, Atarashi K, Manel N, Brodie EL, Shima T et al. 2009. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139:3485–98
    [Google Scholar]
  110. 110.
    Jasion VS, Burnett BP. 2015. Survival and digestibility of orally-administered immunoglobulin preparations containing IgG through the gastrointestinal tract in humans. Nutr. J. 14:22
    [Google Scholar]
  111. 111.
    Jiang R, Du X, Lönnerdal B. 2014. Comparison of bioactivities of talactoferrin and lactoferrins from human and bovine milk. J. Pediatr. Gastroenterol. Nutr. 59:5642–52
    [Google Scholar]
  112. 112.
    Johansson MEV, Jakobsson HE, Holmén-Larsson J, Schütte A, Ermund A et al. 2015. Normalization of host intestinal mucus layers requires long-term microbial colonization. Cell Host Microbe 18:5582–92
    [Google Scholar]
  113. 113.
    Kahn S, Liao Y, Du X, Xu W, Li J, Lönnerdal B. 2018. Exosomal MicroRNAs in milk from mothers delivering preterm infants survive in vitro digestion and are taken up by human intestinal cells. Mol. Nutr. Food Res. 62:11e1701050
    [Google Scholar]
  114. 114.
    Kayama H, Okumura R, Takeda K. 2020. Interaction between the microbiota, epithelia, and immune cells in the intestine. Annu. Rev. Immunol. 38:23–48
    [Google Scholar]
  115. 115.
    Kell DB, Heyden EL, Pretorius E. 2020. The biology of lactoferrin, an iron-binding protein that can help defend against viruses and bacteria. Front. Immunol. 11:1221
    [Google Scholar]
  116. 116.
    Kim CH. 2018. Immune regulation by microbiome metabolites. Immunology 154:2220–29
    [Google Scholar]
  117. 117.
    Koenig JE, Spor A, Scalfone N, Fricker AD, Stombaugh J et al. 2011. Succession of microbial consortia in the developing infant gut microbiome. PNAS 108:Suppl. 14578–85
    [Google Scholar]
  118. 118.
    Koletzko B, Baker S, Cleghorn G, Neto UF, Gopalan S et al. 2005. Global standard for the composition of infant formula: recommendations of an ESPGHAN coordinated international expert group. J. Pediatr. Gastroenterol. Nutr. 41:5584–99
    [Google Scholar]
  119. 119.
    Kong J, Zhang Z, Musch MW, Ning G, Sun J et al. 2008. Novel role of the vitamin D receptor in maintaining the integrity of the intestinal mucosal barrier. Am. J. Physiol. Gastrointest. Liver Physiol. 294:1G208–16
    [Google Scholar]
  120. 120.
    König J, Wells J, Cani PD, García-Ródenas CL, MacDonald T et al. 2016. Human intestinal barrier function in health and disease. Clin. Transl. Gastroenterol. 7:10e196
    [Google Scholar]
  121. 121.
    Koper J, Troise A, Loonen L, Vitaglione P, Capuano E et al. 2022. Tryptophan supplementation increases the production of microbial-derived AhR agonists in an in vitro simulator of intestinal microbial ecosystem. J. Agric. Food Chem. 70:13395868
    [Google Scholar]
  122. 122.
    Kostopoulos I, Elzinga J, Ottman N, Klievink JT, Blijenberg B et al. 2020. Akkermansia muciniphila uses human milk oligosaccharides to thrive in the early life conditions in vitro. Sci. Rep. 10:114330
    [Google Scholar]
  123. 123.
    Kotunia A, Woliński J, Laubitz D, Jurkowska M, Romé V et al. 2004. Effect of sodium butyrate on the small intestine development in neonatal piglets fed by artificial sow. J. Physiol. Pharmacol. 55:Suppl. 259–68
    [Google Scholar]
  124. 124.
    Krumbeck JA, Rasmussen HE, Hutkins RW, Clarke J, Shawron K et al. 2018. Probiotic Bifidobacterium strains and galactooligosaccharides improve intestinal barrier function in obese adults but show no synergism when used together as synbiotics. Microbiome 6:1121
    [Google Scholar]
  125. 125.
    Kuhara T, Yamauchi K, Tamura Y, Okamura H. 2006. Oral administration of lactoferrin increases NK cell activity in mice via increased production of IL-18 and type I IFN in the small intestine. J. Interferon Cytokine Res. 26:7489–99
    [Google Scholar]
  126. 126.
    Kuntz S, Rudloff S, Kunz C. 2008. Oligosaccharides from human milk influence growth-related characteristics of intestinally transformed and non-transformed intestinal cells. Br. J. Nutr. 99:3462–71
    [Google Scholar]
  127. 127.
    Kvistgaard AS, Pallesen LT, Arias CF, López S, Petersen TE et al. 2004. Inhibitory effects of human and bovine milk constituents on rotavirus infections. J. Dairy Sci. 87:124088–96
    [Google Scholar]
  128. 128.
    Laegreid A, Otnaess AB, Fuglesang J. 1986. Human and bovine milk: comparison of ganglioside composition and enterotoxin-inhibitory activity. Pediatr. Res. 20:5416–21
    [Google Scholar]
  129. 129.
    Lagier J-C, Hugon P, Khelaifia S, Fournier P-E, La Scola B, Raoult D 2015. The rebirth of culture in microbiology through the example of culturomics to study human gut microbiota. Clin. Microbiol. Rev. 28:1237–64
    [Google Scholar]
  130. 130.
    Lallès J-P. 2019. Recent advances in intestinal alkaline phosphatase, inflammation, and nutrition. Nutr. Rev. 77:10710–24
    [Google Scholar]
  131. 131.
    Lamas B, Hernandez-Galan L, Galipeau HJ, Constante M, Clarizio A et al. 2020. Aryl hydrocarbon receptor ligand production by the gut microbiota is decreased in celiac disease leading to intestinal inflammation. Sci. Transl. Med. 12:566eaba0624
    [Google Scholar]
  132. 132.
    Lamas B, Natividad JM, Sokol H. 2018. Aryl hydrocarbon receptor and intestinal immunity. Mucosal Immunol 11:41024–38
    [Google Scholar]
  133. 133.
    Laursen MF. 2021. Gut microbiota development: influence of diet from infancy to toddlerhood. Ann. Nutr. Metab. 77:Suppl. 321–34
    [Google Scholar]
  134. 134.
    Lawrence RM, Pane CA. 2007. Human breast milk: current concepts of immunology and infectious diseases. Curr. Probl. Pediatr. Adolesc. Health Care 37:17–36
    [Google Scholar]
  135. 135.
    Le Poul E, Loison C, Struyf S, Springael JY, Lannoy V et al. 2003. Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation. J Biol. Chem. 278:2825481–89
    [Google Scholar]
  136. 136.
    Lee C, Lau E, Chusilp S, Filler R, Li B et al. 2019. Protective effects of vitamin D against injury in intestinal epithelium. Pediatr. Surg. Int. 35:121395–401
    [Google Scholar]
  137. 137.
    Lee H, Padhi E, Hasegawa Y, Larke J, Parenti M et al. 2018. Compositional dynamics of the milk fat globule and its role in infant development. Front. Pediatr. 6:313
    [Google Scholar]
  138. 138.
    Lee S, Goodson ML, Vang W, Rutkowsky J, Kalanetra K et al. 2021. Human milk oligosaccharide 2′-fucosyllactose supplementation improves gut barrier function and signaling in the vagal afferent pathway in mice. Food Funct 12:188507–21
    [Google Scholar]
  139. 139.
    Legrand D. 2016. Overview of lactoferrin as a natural immune modulator. J. Pediatr. 173:Suppl.S10–15
    [Google Scholar]
  140. 140.
    Li B, Hock A, Wu RY, Minich A, Botts SR et al. 2019. Bovine milk–derived exosomes enhance goblet cell activity and prevent the development of experimental necrotizing enterocolitis. PLOS ONE 14:1e0211431
    [Google Scholar]
  141. 141.
    Li Y, Innocentin S, Withers DR, Roberts NA, Gallagher AR et al. 2011. Exogenous stimuli maintain intraepithelial lymphocytes via aryl hydrocarbon receptor activation. Cell 147:3629–40
    [Google Scholar]
  142. 142.
    Liao Y, Du X, Li J, Lonnerdal B. 2017. Human milk exosomes and their microRNAs survive digestion in vitro and are taken up by human intestinal cells. Mol. Nutr. Food Res. 61:111700082
    [Google Scholar]
  143. 143.
    Linden SK, Sutton P, Karlsson NG, Korolik V, McGuckin MA. 2008. Mucins in the mucosal barrier to infection. Mucosal Immunol 1:3183–97
    [Google Scholar]
  144. 144.
    Liu G, Cao W, Jia G, Zhao H, Chen X, Wang J 2018. Calcium-sensing receptor in nutrient sensing: an insight into the modulation of intestinal homoeostasis. Br. J. Nutr. 120:8881–90
    [Google Scholar]
  145. 145.
    Lomax AR, Calder PC. 2009. Prebiotics, immune function, infection and inflammation: a review of the evidence. Br. J. Nutr. 101:5633–58
    [Google Scholar]
  146. 146.
    Lordan C, Thapa D, Ross RP, Cotter PD. 2020. Potential for enriching next-generation health-promoting gut bacteria through prebiotics and other dietary components. Gut Microbes 11:11–20
    [Google Scholar]
  147. 147.
    Loss G, Apprich S, Waser M, Kneifel W, Genuneit J et al. 2011. The protective effect of farm milk consumption on childhood asthma and atopy: the GABRIELA study. J. Allergy Clin. Immunol. 128:4766–73
    [Google Scholar]
  148. 148.
    Loss G, Depner M, Ulfman LH, Van Neerven RJJ, Hose AJ et al. 2015. Consumption of unprocessed cow's milk protects infants from common respiratory infections. J. Allergy Clin. Immunol. 135:156–62
    [Google Scholar]
  149. 149.
    Maares M, Keil C, Straubing S, Robbe-Masselot C, Haase H. 2020. Zinc deficiency disturbs mucin expression, O-glycosylation and secretion by intestinal goblet cells. Int. J. Mol. Sci. 21:176149
    [Google Scholar]
  150. 150.
    Maheshwari A, Kelly DR, Nicola T, Ambalavanan N, Jain SK et al. 2011. TGF-β2 suppresses macrophage cytokine production and mucosal inflammatory responses in the developing intestine. Gastroenterology 140:1242–53
    [Google Scholar]
  151. 151.
    Manoni M, Di Lorenzo C, Ottoboni M, Tretola M, Pinotti L. 2020. Comparative proteomics of milk fat globule membrane (MFGM) proteome across species and lactation stages and the potentials of MFGM fractions in infant formula preparation. Foods 9:91251
    [Google Scholar]
  152. 152.
    Manzanilla EG, Nofrarías M, Anguita M, Castillo M, Perez JF et al. 2006. Effects of butyrate, avilamycin, and a plant extract combination on the intestinal equilibrium of early-weaned pigs. J. Anim. Sci. 84:102743–51
    [Google Scholar]
  153. 153.
    Marino E, Richards JL, McLeod KH, Stanley D, Yap YA et al. 2017. Gut microbial metabolites limit the frequency of autoimmune T cells and protect against type 1 diabetes. Nat. Immunol. 18:5552–62
    [Google Scholar]
  154. 154.
    Martin C, Patel M, Williams S, Arora H, Brawner K, Sims B. 2018. Human breast milk–derived exosomes attenuate cell death in intestinal epithelial cells. Innate Immun 24:5278–84
    [Google Scholar]
  155. 155.
    Martin FPJ, Sprenger N, Montoliu I, Rezzi S, Kochhar S, Nicholson JK. 2010. Dietary modulation of gut functional ecology studied by fecal metabonomics. J. Proteome Res. 9:105284–95
    [Google Scholar]
  156. 156.
    Martin R, Nauta AJ, Ben Amor K, Knippels LMJ, Knol J, Garssen J 2010. Early life: gut microbiota and immune development in infancy. Benef. Microbes 1:4367–82
    [Google Scholar]
  157. 157.
    Martín R, Chain F, Miquel S, Motta J-P, Vergnolle N et al. 2017. Using murine colitis models to analyze probiotics-host interactions. FEMS Microbiol. Rev. 41:Suppl. 1S49–70
    [Google Scholar]
  158. 158.
    Mather IH. 2000. A review and proposed nomenclature for major proteins of the milk-fat globule membrane. J. Dairy Sci. 83:2203–47
    [Google Scholar]
  159. 159.
    Meng D, Sommella E, Salviati E, Campiglia P, Ganguli K et al. 2020. Indole-3-lactic acid, a metabolite of tryptophan, secreted by Bifidobacterium longum subspecies infantis is anti-inflammatory in the immature intestine. Pediatr. Res. 88:2209–17
    [Google Scholar]
  160. 160.
    Mirsepasi-Lauridsen HC, Du Z, Struve C, Charbon G, Karczewski J et al. 2016. Secretion of α-hemolysin by Escherichia coli disrupts tight junctions in ulcerative colitis patients. Clin. Transl. Gastroenterol. 7:3e149
    [Google Scholar]
  161. 161.
    Miyake H, Lee C, Chusilp S, Bhalla M, Li B et al. 2020. Human breast milk exosomes attenuate intestinal damage. Pediatr. Surg. Int. 36:2155–63
    [Google Scholar]
  162. 162.
    Morais J, Marques C, Faria A, Teixeira D, Barreiros-Mota I et al. 2021. Influence of human milk on very preterms’ gut microbiota and alkaline phosphatase activity. Nutrients 13:51564
    [Google Scholar]
  163. 163.
    Moro G, Minoli I, Mosca M, Fanaro S, Jelinek J et al. 2002. Dosage-related bifidogenic effects of galacto- and fructooligosaccharides in formula-fed term infants. J. Pediatr. Gastroenterol. Nutr. 34:3291–95
    [Google Scholar]
  164. 164.
    Morrow AL, Ruiz-Palacios GM, Altaye M, Jiang X, Lourdes Guerrero M et al. 2004. Human milk oligosaccharides are associated with protection against diarrhea in breast-fed infants. J. Pediatr. 145:3297–303
    [Google Scholar]
  165. 165.
    Natividad JM, Agus A, Planchais J, Xavier RJ, Duboc H et al. 2018. Impaired aryl hydrocarbon receptor ligand production by the gut microbiota is a key factor in metabolic syndrome. Cell Metab 28:5737–49.e4
    [Google Scholar]
  166. 166.
    Natividad JM, Rytz A, Keddani S, Bergonzelli G, Garcia-Rodenas CL. 2020. Blends of human milk oligosaccharides confer intestinal epithelial barrier protection in vitro. Nutrients 12:103047
    [Google Scholar]
  167. 167.
    Navarini AA, Krzyzowska M, Lang KS, Horvath E, Hengartner H et al. 2010. Long-lasting immunity by early infection of maternal-antibody-protected infants. Eur. J. Immunol. 40:113–16
    [Google Scholar]
  168. 168.
    Newburg DS, Peterson JA, Ruiz-Palacios GM, Matson DO, Morrow AL et al. 1998. Role of human-milk lactadherin in protection against symptomatic rotavirus infection. Lancet 351:91101160–64
    [Google Scholar]
  169. 169.
    Nguyen DN, Sangild PT, Østergaard MV, Bering SB, Chatterton DEW. 2014. Transforming growth factor-β2 and endotoxin interact to regulate homeostasis via interleukin-8 levels in the immature intestine. Am. J. Physiol. Gastrointest. Liver Physiol. 307:7G689–99
    [Google Scholar]
  170. 170.
    Nilsson Å. 2016. Role of sphingolipids in infant gut health and immunity. J. Pediatr. 173:S53–59
    [Google Scholar]
  171. 171.
    Okubo K, Kamiya M, Urano Y, Nishi H, Herter JM et al. 2016. Lactoferrin suppresses neutrophil extracellular traps release in inflammation. EBioMed 10:204–15
    [Google Scholar]
  172. 172.
    Ooi JH, Li Y, Rogers CJ, Cantorna MT. 2013. Vitamin D regulates the gut microbiome and protects mice from dextran sodium sulfate–induced colitis. J. Nutr. 143:101679–86
    [Google Scholar]
  173. 173.
    Oz HS, Ray M, Chen TS, McClain CJ. 2004. Efficacy of a transforming growth factor β2 containing nutritional support formula in a murine model of inflammatory bowel disease. J. Am. Coll. Nutr. 23:3220–26
    [Google Scholar]
  174. 174.
    Oza S, Lawn JE, Hogan DR, Mathers C, Cousens SN. 2015. Neonatal cause-of-death estimates for the early and late neonatal periods for 194 countries: 2000–2013. Bull. World Health Organ. 93:119–28
    [Google Scholar]
  175. 175.
    Pabst O, Slack E. 2020. IgA and the intestinal microbiota: the importance of being specific. Mucosal Immunol 13:112–21
    [Google Scholar]
  176. 176.
    Paineau D, Respondek F, Menet V, Sauvage R, Bornet F, Wagner A. 2014. Effects of short-chain fructooligosaccharides on faecal bifidobacteria and specific immune response in formula-fed term infants: a randomized, double-blind, placebo-controlled trial. J. Nutr. Sci. Vitaminol. 60:3167–75
    [Google Scholar]
  177. 177.
    Park J-H, Kotani T, Konno T, Setiawan J, Kitamura Y et al. 2016. Promotion of intestinal epithelial cell turnover by commensal bacteria: role of short-chain fatty acids. PLOS ONE 11:5e0156334
    [Google Scholar]
  178. 178.
    Parker P, Sando L, Pearson R, Kongsuwan K, Tellam RL, Smith S. 2010. Bovine Muc1 inhibits binding of enteric bacteria to Caco-2 cells. Glycoconj. J. 27:189–97
    [Google Scholar]
  179. 179.
    Peng L, Li Z-R, Green RS, Holzman IR, Lin J. 2009. Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers. J. Nutr. 139:91619–25
    [Google Scholar]
  180. 180.
    Penttila IA, Flesch IE, McCue AL, Powell BC, Zhou FH et al. 2003. Maternal milk regulation of cell infiltration and interleukin 18 in the intestine of suckling rat pups. Gut 52:111579–86
    [Google Scholar]
  181. 181.
    Perdijk O, van Baarlen P, Fernandez-Gutierrez MM, van den Brink E, Schuren FHJ et al. 2019. Sialyllactose and galactooligosaccharides promote epithelial barrier functioning and distinctly modulate microbiota composition and short chain fatty acid production in vitro. Front. Immunol. 10:94
    [Google Scholar]
  182. 182.
    Perdijk OIJ, van Neerven RJJ, van den Brink E, Meijer B, Savelkoul HFJ, Brugman S. 2018. Bovine lactoferrin inhibits dendritic cell differentiation and induces small intestine homing on T cells Abstr., WIAS Sci. Day, Wageningen Inst. Anim. Sci. Febr. 5
    [Google Scholar]
  183. 183.
    Pérez-Bosque A, Miró L, Maijó M, Polo J, Campbell J et al. 2015. Dietary intervention with serum-derived bovine immunoglobulins protects barrier function in a mouse model of colitis. Am. J. Physiol. Gastrointest. Liver Physiol. 308:12G1012–18
    [Google Scholar]
  184. 184.
    Pérez-Bosque A, Miró L, Maijó M, Polo J, Campbell JM et al. 2016. Oral serum–derived bovine immunoglobulin/protein isolate has immunomodulatory effects on the colon of mice that spontaneously develop colitis. PLOS ONE 11:5e0154823
    [Google Scholar]
  185. 185.
    Peterson JA, Scallan CD, Ceriani RL, Hamosh M. 2001. Structural and functional aspects of three major glycoproteins of the human milk fat globule membrane. Adv. Exp. Med. Biol. 501:179–87
    [Google Scholar]
  186. 186.
    Pickard JM, Zeng MY, Caruso R, Núñez G. 2017. Gut microbiota: role in pathogen colonization, immune responses, and inflammatory disease. Immunol. Rev. 279:170–89
    [Google Scholar]
  187. 187.
    Piewngam P, Otto M. 2020. Probiotics to prevent Staphylococcus aureus disease?. Gut Microbes 11:194–101
    [Google Scholar]
  188. 188.
    Pisano C, Galley J, Elbahrawy M, Wang Y, Farrell A et al. 2020. Human breast milk–derived extracellular vesicles in the protection against experimental necrotizing enterocolitis. J. Pediatr. Surg. 55:154–58
    [Google Scholar]
  189. 189.
    Playford RJ, Floyd DN, Macdonald CE, Calnan DP, Adenekan RO et al. 1999. Bovine colostrum is a health food supplement which prevents NSAID induced gut damage. Gut 44:5653–58
    [Google Scholar]
  190. 190.
    Playford RJ, MacDonald CE, Calnan DP, Floyd DN, Podas T et al. 2001. Co-administration of the health food supplement, bovine colostrum, reduces the acute non-steroidal anti-inflammatory drug–induced increase in intestinal permeability. Clin. Sci. 100:6627–33
    [Google Scholar]
  191. 191.
    Potten CS, Owen G, Hewitt D, Chadwick CA, Hendry H et al. 1995. Stimulation and inhibition of proliferation in the small intestinal crypts of the mouse after in vivo administration of growth factors. Gut 36:6864–73
    [Google Scholar]
  192. 192.
    Poulsen SS, Kryger-Baggesen N, Nexø E. 1996. Immunohistochemical localization of epidermal growth factor in the second-trimester human fetus. Histochem. Cell Biol. 105:2111–17
    [Google Scholar]
  193. 193.
    Qi C, Zhou J, Tu H, Tu R, Chang H et al. 2022. Lactation-dependent vertical transmission of natural probiotics from the mother to the infant gut through breast milk. Food Funct 13:1304–15
    [Google Scholar]
  194. 194.
    Qiu J, Heller JJ, Guo X, Chen ZE, Fish K et al. 2012. The aryl hydrocarbon receptor regulates gut immunity through modulation of innate lymphoid cells. Immunity 36:192–104
    [Google Scholar]
  195. 195.
    Quintana FJ, Basso AS, Iglesias AH, Korn T, Farez MF et al. 2008. Control of Treg and TH17 cell differentiation by the aryl hydrocarbon receptor. Nature 453:719165–71
    [Google Scholar]
  196. 196.
    Rasmussen SO, Martin L, Østergaard MV, Rudloff S, Roggenbuck M et al. 2017. Human milk oligosaccharide effects on intestinal function and inflammation after preterm birth in pigs. J. Nutr. Biochem. 40:141–54
    [Google Scholar]
  197. 197.
    Rautava S, Lu L, Nanthakumar NN, Dubert-Ferrandon A, Walker WA. 2012. TGF-β2 induces maturation of immature human intestinal epithelial cells and inhibits inflammatory cytokine responses induced via the NF-κB pathway. J. Pediatr. Gastroenterol. Nutr. 54:5630–38
    [Google Scholar]
  198. 198.
    Reinhardt TA, Lippolis JD, Nonnecke BJ, Sacco RE. 2012. Bovine milk exosome proteome. J. Proteom. 75:51486–92
    [Google Scholar]
  199. 199.
    Reznikov EA, Comstock SS, Yi C, Contractor N, Donovan SM. 2014. Dietary bovine lactoferrin increases intestinal cell proliferation in neonatal piglets. J. Nutr. 144:91401–8
    [Google Scholar]
  200. 200.
    Riedler J, Braun-Fahrländer C, Eder W, Schreuer M, Waser M et al. 2001. Exposure to farming in early life and development of asthma and allergy: a cross-sectional survey. Lancet 358:92881129–33
    [Google Scholar]
  201. 201.
    Rodríguez JM, Murphy K, Stanton C, Ross RP, Kober OI et al. 2015. The composition of the gut microbiota throughout life, with an emphasis on early life. Microb. Ecol. Health Dis. 26:26050
    [Google Scholar]
  202. 202.
    Rossi O, Khan MT, Schwarzer M, Hudcovic T, Srutkova D et al. 2015. Faecalibacterium prausnitzii strain HTF-F and its extracellular polymeric matrix attenuate clinical parameters in DSS-induced colitis. PLOS ONE 10:4e0123013
    [Google Scholar]
  203. 203.
    Round JL, Mazmanian SK. 2009. The gut microbiota shapes intestinal immune responses during health and disease. Nat. Rev. Immunol. 9:5313–23
    [Google Scholar]
  204. 204.
    Rump JA, Arndt R, Arnold A, Bendick C, Dichtelmuller H et al. 1992. Treatment of diarrhoea in human immunodeficiency virus–infected patients with immunoglobulins from bovine colostrum. Clin. Investig. 70:7588–94
    [Google Scholar]
  205. 205.
    Ryz NR, Lochner A, Bhullar K, Ma C, Huang T et al. 2015. Dietary vitamin D3 deficiency alters intestinal mucosal defense and increases susceptibility to Citrobacter rodentium–induced colitis. Am. J. Physiol. Gastrointest. Liver Physiol. 309:9G730–42
    [Google Scholar]
  206. 206.
    Sahay T, Ananthakrishnan AN. 2014. Vitamin D deficiency is associated with community-acquired Clostridium difficile infection: a case-control study. BMC Infect. Dis. 14:661
    [Google Scholar]
  207. 207.
    Salminen S, Collado MC, Endo A, Hill C, Lebeer S et al. 2021. The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics. Nat. Rev. Gastroenterol. Hepatol. 18:9649–67
    [Google Scholar]
  208. 208.
    Sarkar P, Saha T, Sheikh IA, Chakraborty S, Aoun J et al. 2019. Zinc ameliorates intestinal barrier dysfunctions in shigellosis by reinstating claudin-2 and -4 on the membranes. Am. J. Physiol. Gastrointest. Liver Physiol. 316:2G229–46
    [Google Scholar]
  209. 209.
    Scholtens PA, Alliet P, Raes M, Alles MS, Kroes H et al. 2008. Fecal secretory immunoglobulin A is increased in healthy infants who receive a formula with short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides. J. Nutr. 138:61141–47
    [Google Scholar]
  210. 210.
    Seno H, Sawada M, Fukuzawa H, Morita Y, Takaishi S et al. 2001. Enhanced expression of transforming growth factor (TGF)-α precursor and TGF-β1 during Paneth cell regeneration. Dig. Dis. Sci. 46:51004–10
    [Google Scholar]
  211. 211.
    Shao Y, Wolf PG, Guo S, Guo Y, Gaskins HR, Zhang B. 2017. Zinc enhances intestinal epithelial barrier function through the PI3K/AKT/mTOR signaling pathway in Caco-2 cells. J. Nutr. Biochem. 43:18–26
    [Google Scholar]
  212. 212.
    Sharif S, Meader N, Oddie SJ, Rojas-Reyes MX, McGuire W 2020. Probiotics to prevent necrotising enterocolitis in very preterm or very low birth weight infants. Cochrane Database Syst. Rev. 10:10CD005496
    [Google Scholar]
  213. 213.
    Shi N, Li N, Duan X, Niu H. 2017. Interaction between the gut microbiome and mucosal immune system. Mil. Med. Res. 4:14
    [Google Scholar]
  214. 214.
    Shi Y, Cui X, Sun Y, Zhao Q, Liu T. 2020. Intestinal vitamin D receptor signaling ameliorates dextran sulfate sodium–induced colitis by suppressing necroptosis of intestinal epithelial cells. FASEB J 34:1013494–506
    [Google Scholar]
  215. 215.
    Shield J, Melville C, Novelli V, Anderson G, Scheimberg I et al. 1993. Bovine colostrum immunoglobulin concentrate for cryptosporidiosis in AIDS. Arch. Dis. Child 69:4451–53
    [Google Scholar]
  216. 216.
    Sierra C, Bernal M-J, Blasco J, Martínez R, Dalmau J et al. 2014. Prebiotic effect during the first year of life in healthy infants fed formula containing GOS as the only prebiotic: a multicentre, randomised, double-blind and placebo-controlled trial. Eur. J. Nutr. 54:189–99
    [Google Scholar]
  217. 217.
    Singh N, Gurav A, Sivaprakasam S, Brady E, Padia R et al. 2014. Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity 40:1128–39
    [Google Scholar]
  218. 218.
    Siqueiros-Cendón T, Arévalo-Gallegos S, Iglesias-Figueroa BF, García-Montoya IA, Salazar-Martínez J, Rascón-Cruz Q. 2014. Immunomodulatory effects of lactoferrin. Acta Pharmacol. Sin. 35:5557–66
    [Google Scholar]
  219. 219.
    Smith PM, Howitt MR, Panikov N, Michaud M, Gallini CA et al. 2013. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 341:6145569–73
    [Google Scholar]
  220. 220.
    Sodhi CP, Wipf P, Yamaguchi Y, Fulton WB, Kovler M et al. 2021. 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. 89:191–101
    [Google Scholar]
  221. 221.
    Song BJ, Jouni ZE, Ferruzzi MG. 2013. Assessment of phytochemical content in human milk during different stages of lactation. Nutrition 29:1195–202
    [Google Scholar]
  222. 222.
    Sonnenberg GF, Fouser LA, Artis D. 2011. Border patrol: regulation of immunity, inflammation and tissue homeostasis at barrier surfaces by IL-22. Nat. Immunol. 12:5383–90
    [Google Scholar]
  223. 223.
    Sovran B, Loonen LMP, Lu P, Hugenholtz F, Belzer C et al. 2015. IL-22–STAT3 pathway plays a key role in the maintenance of ileal homeostasis in mice lacking secreted mucus barrier. Inflamm. Bowel Dis. 21:3531–42
    [Google Scholar]
  224. 224.
    Sozańska B, Pearce N, Dudek K, Cullinan P. 2013. Consumption of unpasteurized milk and its effects on atopy and asthma in children and adult inhabitants in rural Poland. Allergy 68:5644–50
    [Google Scholar]
  225. 225.
    Spitsberg VL. 2005. Bovine milk fat globule membrane as a potential nutraceutical. J. Dairy Sci. 88:72289–94
    [Google Scholar]
  226. 226.
    Sprong R, Hulstein M, Van Der Meer R. 2002. Bovine milk fat components inhibit food-borne pathogens. Int. Dairy J. 12:2–3209–15
    [Google Scholar]
  227. 227.
    Stockinger B, Di Meglio P, Gialitakis M, Duarte JH. 2014. The aryl hydrocarbon receptor: multitasking in the immune system. Annu. Rev. Immunol. 32:403–32
    [Google Scholar]
  228. 228.
    Struijs K, Van de Wiele T, Le TT, Debyser G, Dewettinck K et al. 2013. Milk fat globule membrane glycoproteins prevent adhesion of the colonic microbiota and result in increased bacterial butyrate production. Int. Dairy J. 32:299–109
    [Google Scholar]
  229. 229.
    Šuligoj T, Vigsnæs LK, Van den Abbeele P, Apostolou A, Karalis K et al. 2020. Effects of human milk oligosaccharides on the adult gut microbiota and barrier function. Nutrients 12:92808
    [Google Scholar]
  230. 230.
    Sun J, Marwah G, Westgarth M, Buys N, Ellwood D, Gray PH 2017. Effects of probiotics on necrotizing enterocolitis, sepsis, intraventricular hemorrhage, mortality, length of hospital stay, and weight gain in very preterm infants: a meta-analysis. Adv. Nutr. 8:5749–63
    [Google Scholar]
  231. 231.
    Suzuki YA, Shin K, Lönnerdal B. 2001. Molecular cloning and functional expression of a human intestinal lactoferrin receptor. Biochemistry 40:5115771–79
    [Google Scholar]
  232. 232.
    Tanaka M, Nakayama J. 2017. Development of the gut microbiota in infancy and its impact on health in later life. Allergol. Int. 66:4515–22
    [Google Scholar]
  233. 233.
    Tao N, DePeters EJ, Freeman S, German JB, Grimm R, Lebrilla CB. 2008. Bovine milk glycome. J. Dairy Sci. 91:103768–78
    [Google Scholar]
  234. 234.
    Tarnow-Mordi WO, Abdel-Latif ME, Martin A, Pammi M, Robledo K et al. 2020. The effect of lactoferrin supplementation on death or major morbidity in very low birthweight infants (LIFT): a multicentre, double-blind, randomised controlled trial. Lancet Child Adolesc. Health 4:6444–54
    [Google Scholar]
  235. 235.
    Ten Bruggencate SJ, Frederiksen PD, Pedersen SM, Floris-Vollenbroek EG, Lucas–van de Bos E et al. 2016. Dietary milk-fat-globule membrane affects resistance to diarrheagenic Escherichia coli in healthy adults in a randomized, placebo-controlled, double-blind study. J. Nutr. 146:2249–55
    [Google Scholar]
  236. 236.
    Thänert R, Keen EC, Dantas G, Warner BB, Tarr PI. 2021. Necrotizing enterocolitis and the microbiome: current status and future directions. J. Infect. Dis. 223:12 Suppl. 2S257–63
    [Google Scholar]
  237. 237.
    Thangaraju M, Cresci GA, Liu K, Ananth S, Gnanaprakasam JP et al. 2009. GPR109A is a G-protein-coupled receptor for the bacterial fermentation product butyrate and functions as a tumor suppressor in colon. Cancer Res 69:72826–32
    [Google Scholar]
  238. 238.
    Thorburn AN, McKenzie CI, Shen S, Stanley D, Macia L et al. 2015. Evidence that asthma is a developmental origin disease influenced by maternal diet and bacterial metabolites. Nat. Commun. 6:7320
    [Google Scholar]
  239. 239.
    Tian S, Wang J, Yu H, Wang J, Zhu W 2018. Effects of galacto-oligosaccharides on growth and gut function of newborn suckling piglets. J. Anim. Sci. Biotechnol. 9:75
    [Google Scholar]
  240. 240.
    Torow N, Hornef MW. 2017. The neonatal window of opportunity: setting the stage for life-long host-microbial interaction and immune homeostasis. J. Immunol. 198:2557–63
    [Google Scholar]
  241. 241.
    Torow N, Marsland BJ, Hornef MW, Gollwitzer ES. 2017. Neonatal mucosal immunology. Mucosal Immunol. 10:15–17
    [Google Scholar]
  242. 242.
    Triantis V, Bode L, van Neerven RJJ. 2018. Immunological effects of human milk oligosaccharides. Front. Pediatr. 6:190
    [Google Scholar]
  243. 243.
    Troost FJ, Steijns J, Saris WH, Brummer RJ. 2001. Gastric digestion of bovine lactoferrin in vivo in adults. J. Nutr. 131:82101–4
    [Google Scholar]
  244. 244.
    Tuin A, Poelstra K, Bok L, Raaben W, Velders MP, Dijkstra G. 2009. Role of alkaline phosphatase in colitis in man and rats. Gut 58:3379–87
    [Google Scholar]
  245. 245.
    Turfkruyer M, Verhasselt V. 2015. Breast milk and its impact on maturation of the neonatal immune system. Curr. Opin. Infect. Dis. 28:3199–206
    [Google Scholar]
  246. 246.
    Ulfman LH, Leusen JHW, Savelkoul HFJ, Warner JO, van Neerven RJJ. 2018. Effects of bovine immunoglobulins on immune function, allergy, and infection. Front. Nutr. 5:52
    [Google Scholar]
  247. 247.
    Van de Pavert SA, Mebius RE 2010. New insights into the development of lymphoid tissues. Nat. Rev. Immunol. 10:9664–74
    [Google Scholar]
  248. 248.
    Van Neerven R. 2021. Nutritional composition comprising milk fat and immunoglobulin WO Patent Appl WO2021013862 (A1)
    [Google Scholar]
  249. 249.
    Van Neerven RJJ, Albers R, Wichers H, Garssen J, Savelkoul HFJ. 2017. Voeding en immuniteit: kan voeding bijdragen aan het voorkomen van allergie, infectie en ontsteking? [Nutrition and immunity: Can nutrition contribute to the prevention of allergy, infection and inflammation?. ] Ned. Tijdschr. Allerg. Astma 17:21–28
    [Google Scholar]
  250. 250.
    Van Neerven RJJ, Knol EF, Heck JML, Savelkoul HFJ. 2012. Which factors in raw cow's milk contribute to protection against allergies?. J. Allergy Clin. Immunol. 130:4853–58
    [Google Scholar]
  251. 251.
    Verhasselt V, Milcent V, Cazareth J, Kanda A, Fleury S et al. 2008. Breast milk–mediated transfer of an antigen induces tolerance and protection from allergic asthma. Nat. Med. 214:2170–75
    [Google Scholar]
  252. 252.
    Wang J, Tian S, Yu H, Wang J, Zhu W 2019. Response of colonic mucosa–associated microbiota composition, mucosal immune homeostasis, and barrier function to early life galactooligosaccharides intervention in suckling piglets. J. Agric. Food Chem. 67:2578–88
    [Google Scholar]
  253. 253.
    Wang T-T, Nestel FP, Bourdeau V, Nagai Y, Wang Q et al. 2004. Cutting edge: 1,25-Dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J. Immunol. 173:52909–12
    [Google Scholar]
  254. 254.
    Wang X, Valenzano MC, Mercado JM, Zurbach EP, Mullin JM. 2013. Zinc supplementation modifies tight junctions and alters barrier function of CACO-2 human intestinal epithelial layers. Dig. Dis. Sci. 58:177–87
    [Google Scholar]
  255. 255.
    Wang X, Yan X, Zhang L, Cai J, Zhou Y et al. 2019. Identification and peptidomic profiling of exosomes in preterm human milk: insights into necrotizing enterocolitis prevention. Mol. Nutr. Food Res. 63:e1801247
    [Google Scholar]
  256. 256.
    Wang Y, Zou Y, Wang J, Ma H, Zhang B, Wang S 2020. The protective effects of 2′-fucosyllactose against E. coli O157 infection are mediated by the regulation of gut microbiota and the inhibition of pathogen adhesion. Nutrients 12:51284
    [Google Scholar]
  257. 257.
    Waser M, Michels KB, Bieli C, Flöistrup H, Pershagen G et al. 2007. Inverse association of farm milk consumption with asthma and allergy in rural and suburban populations across Europe. Clin. Exp. Allergy 37:5661–70
    [Google Scholar]
  258. 258.
    Watson D, O'Connell Motherway M, Schoterman MHC, van Neerven RJJ, Nauta A, Van Sinderen D 2013. Selective carbohydrate utilization by lactobacilli and bifidobacteria. J. Appl. Microbiol. 114:41132–46
    [Google Scholar]
  259. 259.
    Watterlot L, Lakhdari O, Bermu LG, Sokol H, Bridonneau C et al. 2008. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. PNAS 105:4316731–36
    [Google Scholar]
  260. 260.
    Wells JM. 2011. Immunomodulatory mechanisms of lactobacilli. Microb. Cell Fact. 10:Suppl. 117
    [Google Scholar]
  261. 261.
    Wells JM, Brummer RJ, Derrien M, MacDonald TT, Troost F et al. 2017. Homeostasis of the gut barrier and potential biomarkers. Am. J. Physiol. Gastrointest. Liver Physiol. 312:3G171–93
    [Google Scholar]
  262. 262.
    Weström B, Arévalo Sureda E, Pierzynowska K, Pierzynowski SG, Pérez-Cano FJ 2020. The immature gut barrier and its importance in establishing immunity in newborn mammals. Front. Immunol. 11:1153
    [Google Scholar]
  263. 263.
    Whitehouse JS, Riggle KM, Purpi DP, Mayer AN, Pritchard KA Jr. et al. 2010. The protective role of intestinal alkaline phosphatase in necrotizing enterocolitis. J. Surg. Res. 163:179–85
    [Google Scholar]
  264. 264.
    Wieërs G, Belkhir L, Enaud R, Leclercq S, Philippart de Foy J-M et al. 2019. How probiotics affect the microbiota. Front. Cell. Infect. Microbiol. 9:454
    [Google Scholar]
  265. 265.
    Willemsen LEM, Koetsier MA, Balvers M, Beermann C, Stahl B, van Tol EAF. 2008. Polyunsaturated fatty acids support epithelial barrier integrity and reduce IL-4 mediated permeability in vitro. Eur. J. Nutr. 47:4183–91
    [Google Scholar]
  266. 266.
    Wilson CB, Kollmann TR. 2008. Induction of antigen-specific immunity in human neonates and infants. Nestle Nutr. Workshop Ser. Pediatr. Prog. 61:183–95
    [Google Scholar]
  267. 267.
    Wolf T, Baier SR, Zempleni J. 2015. The intestinal transport of bovine milk exosomes is mediated by endocytosis in human colon carcinoma Caco-2 cells and rat small intestinal IEC-6 cells. J. Nutr. 145:102201–6
    [Google Scholar]
  268. 268.
    Woliński J, Słupecka M, Weström B, Prykhodko O, Ochniewicz P et al. 2012. Effect of feeding colostrum versus exogenous immunoglobulin G on gastrointestinal structure and enteric nervous system in newborn pigs. J. Anim. Sci. 90:Suppl. 4327–30
    [Google Scholar]
  269. 269.
    WHO/UNICEF 2003. Global strategy for infant and young child feeding Glob. Strategy WHO/UNICEF
    [Google Scholar]
  270. 270.
    Xiao L, Cui T, Liu S, Chen B, Wang Y et al. 2019. Vitamin A supplementation improves the intestinal mucosal barrier and facilitates the expression of tight junction proteins in rats with diarrhea. Nutrition 57:97–108
    [Google Scholar]
  271. 271.
    Xiao S, Li Q, Hu K, He Y, Ai Q et al. 2018. Vitamin A and retinoic acid exhibit protective effects on necrotizing enterocolitis by regulating intestinal flora and enhancing the intestinal epithelial barrier. Arch. Med. Res. 49:11–9
    [Google Scholar]
  272. 272.
    Xie M-Y, Hou L-J, Sun J-J, Zeng B, Xi Q-Y et al. 2019. Porcine milk exosome miRNAs attenuate LPS-induced apoptosis through inhibiting TLR4/NF-κB and p53 pathways in intestinal epithelial cells. J. Agric. Food Chem. 67:349477–91
    [Google Scholar]
  273. 273.
    Yang C, Zhu X, Liu N, Chen Y, Gan H et al. 2014. Lactoferrin up-regulates intestinal gene expression of brain-derived neurotrophic factors BDNF, UCHL1 and alkaline phosphatase activity to alleviate early weaning diarrhea in postnatal piglets. J. Nutr. Biochem. 25:8834–42
    [Google Scholar]
  274. 274.
    Yang Y, Rader E, Peters-Carr M, Bent RC, Smilowitz JT et al. 2019. Ontogeny of alkaline phosphatase activity in infant intestines and breast milk. BMC Pediatr 19:12
    [Google Scholar]
  275. 275.
    Yu Z-T, Chen C, Newburg DS 2013. Utilization of major fucosylated and sialylated human milk oligosaccharides by isolated human gut microbes. Glycobiology 23:111281–92
    [Google Scholar]
  276. 276.
    Yu Z-T, Nanthakumar NN, Newburg DS. 2016. 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. 146:101980–90
    [Google Scholar]
  277. 277.
    Zavaleta N, Kvistgaard AS, Staudt A, Graverholt G, Respicio G et al. 2011. Efficacy of a complementary food enriched with a milk fat globule membrane protein fraction on diarrhea, anemia and micronutrient status in infants. J. Pediatr. Gastroenterol. Nutr. 53:5561–68
    [Google Scholar]
  278. 278.
    Zempleni J, Aguilar-Lozano A, Sadri M, Sukreet S, Manca S et al. 2017. Biological activities of extracellular vesicles and their cargos from bovine and human milk in humans and implications for infants. J. Nutr. 147:13–10
    [Google Scholar]
  279. 279.
    Zhao Y, Chen F, Wu W, Sun M, Bilotta AJ et al. 2018. GPR43 mediates microbiota metabolite SCFA regulation of antimicrobial peptide expression in intestinal epithelial cells via activation of mTOR and STAT3. Mucosal Immunol 11:3752–62
    [Google Scholar]
  280. 280.
    Zhong W, McClain CJ, Cave M, Kang YJ, Zhou Z. 2010. The role of zinc deficiency in alcohol-induced intestinal barrier dysfunction. Am. J. Physiol. Gastrointest. Liver Physiol. 298:5G625–33
    [Google Scholar]
  281. 281.
    Zihni C, Mills C, Matter K, Balda MS. 2016. Tight junctions: from simple barriers to multifunctional molecular gates. Nat. Rev. Mol. Cell Biol. 17:9564–80
    [Google Scholar]
  282. 282.
    Zinkernagel RM. 2001. Maternal antibodies, childhood infections, and autoimmune diseases. N. Engl. J. Med. 345:181331–35
    [Google Scholar]
  283. 283.
    Zonneveld MI, van Herwijnen MJC, Fernandez-Gutierrez MM, Giovanazzi A, de Groot AM et al. 2021. Human milk extracellular vesicles target nodes in interconnected signalling pathways that enhance oral epithelial barrier function and dampen immune responses. J. Extracell. Vesicles 10:5e12071
    [Google Scholar]
/content/journals/10.1146/annurev-nutr-122221-103916
Loading
/content/journals/10.1146/annurev-nutr-122221-103916
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error