Pediatr Gastroenterol Hepatol Nutr.  2020 Jan;23(1):1-14. 10.5223/pghn.2020.23.1.1.

Prebiotics in the Infant Microbiome: The Past, Present, and Future

Affiliations
  • 1Department of Pediatric, Sheikh Khalifa Medical City, Abu Dhabi, UAE. msmiqdady@yahoo.com

Abstract

The latest definition of a prebiotic is "a substrate that is selectively utilized by host microorganisms conferring a health benefit"; it now includes non-food elements and is applicable to extra-intestinal tissues. Prebiotics are recognized as a promising tool in the promotion of general health and in the prevention and treatment of numerous juvenile diseases. Prebiotics are considered an immunoactive agent, with the potential for long-lasting effects extending past active administration of the prebiotic. Because of its extremely low risk of serious adverse effects, ease of administration, and strong potential for influencing the composition and function of the microbiota in the gut and beyond, the beneficial clinical applications of prebiotics are expanding. Prebiotics are the third largest component of human breast milk. Preparations including galactooligosaccharides (GOS), fructooligosaccharides (FOS), 2"²-fucosyllactose, lacto-N-neo-tetraose are examples of commonly used and studied products for supplementation in baby formula. In particular, the GOS/FOS combination is the most studied. Maintaining a healthy microbiome is essential to promote homeostasis of the gut and other organs. With more than 1,000 different microbial species in the gut, it is likely more feasible to modify the gut microbiota through the use of certain prebiotic mixtures rather than supplementing with a particular probiotic strain. In this review, we discuss the latest clinical evidence regarding prebiotics and its role in gut immunity, allergy, infections, inflammation, and functional gastrointestinal disorders.

Keyword

Prebiotics; Gut heath; Functional gastrointestinal disorders; Probiotics; Human milk oligosaccharides

MeSH Terms

Gastrointestinal Diseases
Gastrointestinal Microbiome
Homeostasis
Humans
Hypersensitivity
Infant Formula
Infant*
Inflammation
Microbiota*
Milk, Human
Prebiotics*
Probiotics
Prebiotics

Figure

  • Fig. 1 Flow diagram highlighting common natural and synthetic sources of prebiotics. CLAs: conjugated linoleic acid, FOS: fructooligosaccharides.

  • Fig. 2 Schematic demonstrating the mechanism of action and potential health benefits of prebiotics.


Reference

1. Weiner HL. Oral tolerance, an active immunologic process mediated by multiple mechanisms. J Clin Invest. 2000; 106:935–937. PMID: 11032852.
Article
2. Faria AM, Weiner HL. Oral tolerance. Immunol Rev. 2005; 206:232–259. PMID: 16048553.
Article
3. Vighi G, Marcucci F, Sensi L, Di Cara G, Frati F. Allergy and the gastrointestinal system. Clin Exp Immunol. 2008; 153(Suppl 1):3–6. PMID: 18721321.
Article
4. Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006; 444:1027–1031. PMID: 17183312.
Article
5. Tilg H, Kaser A. Gut microbiome, obesity, and metabolic dysfunction. J Clin Invest. 2011; 121:2126–2132. PMID: 21633181.
Article
6. Manichanh C, Borruel N, Casellas F, Guarner F. The gut microbiota in IBD. Nat Rev Gastroenterol Hepatol. 2012; 9:599–608. PMID: 22907164.
Article
7. Ley RE, Peterson DA, Gordon JI. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell. 2006; 124:837–848. PMID: 16497592.
Article
8. Iebba V, Totino V, Gagliardi A, Santangelo F, Cacciotti F, Trancassini M, et al. Eubiosis and dysbiosis: the two sides of the microbiota. New Microbiol. 2016; 39:1–12. PMID: 26922981.
9. Hansen R, Scott KP, Khan S, Martin JC, Berry SH, Stevenson M, et al. First-pass meconium samples from healthy term vaginally-delivered neonates: an analysis of the microbiota. PLoS One. 2015; 10:e0133320. PMID: 26218283.
Article
10. Aagaard K, Ma J, Antony KM, Ganu R, Petrosino J, Versalovic J. The placenta harbors a unique microbiome. Sci Transl Med. 2014; 6:237ra65.
Article
11. Perez-Muñoz ME, Arrieta MC, Ramer-Tait AE, Walter J. A critical assessment of the “sterile womb” and “in utero colonization” hypotheses: implications for research on the pioneer infant microbiome. Microbiome. 2017; 5:48. PMID: 28454555.
Article
12. Adlerberth I, Wold AE. Establishment of the gut microbiota in Western infants. Acta Paediatr. 2009; 98:229–238. PMID: 19143664.
Article
13. Biasucci G, Benenati B, Morelli L, Bessi E, Boehm G. Cesarean delivery may affect the early biodiversity of intestinal bacteria. J Nutr. 2008; 138:1796S–800S. PMID: 18716189.
Article
14. Grönlund MM, Lehtonen OP, Eerola E, Kero P. Fecal microflora in healthy infants born by different methods of delivery: permanent changes in intestinal flora after cesarean delivery. J Pediatr Gastroenterol Nutr. 1999; 28:19–25. PMID: 9890463.
15. Huurre A, Kalliomäki M, Rautava S, Rinne M, Salminen S, Isolauri E. Mode of delivery - effects on gut microbiota and humoral immunity. Neonatology. 2008; 93:236–240. PMID: 18025796.
Article
16. Mackie RI, Sghir A, Gaskins HR. Developmental microbial ecology of the neonatal gastrointestinal tract. Am J Clin Nutr. 1999; 69:1035S–1045S. PMID: 10232646.
Article
17. Benno Y, Sawada K, Mitsuoka T. The intestinal microflora of infants: composition of fecal flora in breast-fed and bottle-fed infants. Microbiol Immunol. 1984; 28:975–986. PMID: 6513816.
Article
18. Penders J, Stobberingh EE, Thijs C, Adams H, Vink C, van Ree R, et al. Molecular fingerprinting of the intestinal microbiota of infants in whom atopic eczema was or was not developing. Clin Exp Allergy. 2006; 36:1602–1608. PMID: 17177684.
Article
19. Harmsen HJ, Wildeboer-Veloo AC, Raangs GC, Wagendorp AA, Klijn N, Bindels JG, et al. Analysis of intestinal flora development in breast-fed and formula-fed infants by using molecular identification and detection methods. J Pediatr Gastroenterol Nutr. 2000; 30:61–67. PMID: 10630441.
Article
20. Favier CF, Vaughan EE, De Vos WM, Akkermans AD. Molecular monitoring of succession of bacterial communities in human neonates. Appl Environ Microbiol. 2002; 68:219–226. PMID: 11772630.
Article
21. Penders J, Thijs C, Vink C, Stelma FF, Snijders B, Kummeling I, et al. Factors influencing the composition of the intestinal microbiota in early infancy. Pediatrics. 2006; 118:511–521. PMID: 16882802.
Article
22. Li M, Wang M, Donovan SM. Early development of the gut microbiome and immune-mediated childhood disorders. Semin Reprod Med. 2014; 32:74–86. PMID: 24390924.
Article
23. Coppa GV, Zampini L, Galeazzi T, Gabrielli O. Prebiotics in human milk: a review. Dig Liver Dis. 2006; 38(Suppl 2):S291–S294. PMID: 17259094.
Article
24. Kunz C, Rudloff S, Baier W, Klein N, Strobel S. Oligosaccharides in human milk: structural, functional, and metabolic aspects. Annu Rev Nutr. 2000; 20:699–722. PMID: 10940350.
Article
25. Bode L. The functional biology of human milk oligosaccharides. Early Hum Dev. 2015; 91:619–622. PMID: 26375354.
Article
26. McGuire MK, Meehan CL, McGuire MA, Williams JE, Foster J, Sellen DW, et al. What's normal? Oligosaccharide concentrations and profiles in milk produced by healthy women vary geographically. Am J Clin Nutr. 2017; 105:1086–1100. PMID: 28356278.
Article
27. Garrido D, Kim JH, German JB, Raybould HE, Mills DA. Oligosaccharide binding proteins from Bifidobacterium longum subsp. infantis reveal a preference for host glycans. PLoS One. 2011; 6:e17315. PMID: 21423604.
Article
28. Miliku K, Robertson B, Sharma AK, Subbarao P, Becker AB, Mandhane PJ, et al. CHILD Study Investigators. Bode L, Azad MB. Human milk oligosaccharide profiles and food sensitization among infants in the CHILD Study. Allergy. 2018; 73:2070–2073. PMID: 29775217.
29. Roberfroid M, Gibson GR, Hoyles L, McCartney AL, Rastall R, Rowland I, et al. Prebiotic effects: metabolic and health benefits. Br J Nutr. 2010; 104(Suppl 2):S1–S63.
Article
30. Stewart ML, Timm DA, Slavin JL. Fructooligosaccharides exhibit more rapid fermentation than long-chain inulin in an in vitro fermentation system. Nutr Res. 2008; 28:329–334. PMID: 19083428.
Article
31. Rastall RA, Gibson GR. Recent developments in prebiotics to selectively impact beneficial microbes and promote intestinal health. Curr Opin Biotechnol. 2015; 32:42–46. PMID: 25448231.
Article
32. Moro G, Boehm G. Clinical outcomes of prebiotic intervention trials during infancy: a review. Functional Food Rev. 2012; 4:101–113.
33. Newburg DS. Oligosaccharides in human milk and bacterial colonization. J Pediatr Gastroenterol Nutr. 2000; 30(Suppl 2):S8–S17. PMID: 10749396.
Article
34. Braegger C, Chmielewska A, Decsi T, Kolacek S, Mihatsch W, Moreno L, et al. ESPGHAN Committee on Nutrition. Supplementation of infant formula with probiotics and/or prebiotics: a systematic review and comment by the ESPGHAN committee on nutrition. J Pediatr Gastroenterol Nutr. 2011; 52:238–250. PMID: 21150647.
Article
35. Gibson GR, Roberfroid MB. Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. J Nutr. 1995; 125:1401–1412. PMID: 7782892.
Article
36. Gibson GR, Probert HM, Loo JV, Rastall RA, Roberfroid MB. Dietary modulation of the human colonic microbiota: updating the concept of prebiotics. Nutr Res Rev. 2004; 17:259–275. PMID: 19079930.
Article
37. Gibson GR, Scott KP, Rastall RA, Tuohy KM, Hotchkiss A, Dubert-Ferrandon A, et al. Dietary prebiotics: current status and new definition. Food Sci Tech Bull Funct Food. 2010; 7:1–19.
Article
38. Bindels LB, Delzenne NM, Cani PD, Walter J. Towards a more comprehensive concept for prebiotics. Nat Rev Gastroenterol Hepatol. 2015; 12:303–310. PMID: 25824997.
Article
39. Gibson GR, Hutkins R, Sanders ME, Prescott SL, Reimer RA, Salminen SJ, et al. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat Rev Gastroenterol Hepatol. 2017; 14:491–502. PMID: 28611480.
Article
40. Parnell JA, Reimer RA. Prebiotic fibres dose-dependently increase satiety hormones and alter Bacteroidetes and Firmicutes in lean and obese JCR:LA-cp rats. Br J Nutr. 2012; 107:601–613. PMID: 21767445.
Article
41. Wasilewski A, Zielińska M, Storr M, Fichna J. Beneficial effects of probiotics, prebiotics, synbiotics, and psychobiotics in inflammatory bowel disease. Inflamm Bowel Dis. 2015; 21:1674–1682. PMID: 25822014.
Article
42. Jakobsdottir G, Nyman M, Fåk F. Designing future prebiotic fiber to target metabolic syndrome. Nutrition. 2014; 30:497–502. PMID: 24262515.
Article
43. Barcelo A, Claustre J, Moro F, Chayvialle JA, Cuber JC, Plaisancié P. Mucin secretion is modulated by luminal factors in the isolated vascularly perfused rat colon. Gut. 2000; 46:218–224. PMID: 10644316.
Article
44. Gibson GR, McCartney AL, Rastall RA. Prebiotics and resistance to gastrointestinal infections. Br J Nutr. 2005; 93(Suppl 1):S31–S34. PMID: 15877892.
Article
45. Shoaf K, Mulvey GL, Armstrong GD, Hutkins RW. Prebiotic galactooligosaccharides reduce adherence of enteropathogenic Escherichia coli to tissue culture cells. Infect Immun. 2006; 74:6920–6928. PMID: 16982832.
46. Shokryazdan P, Faseleh Jahromi M, Navidshad B, Liang JB. Effects of prebiotics on immune system and cytokine expression. Med Microbiol Immunol. 2017; 206:1–9. PMID: 27704207.
Article
47. Klampfer L, Huang J, Sasazuki T, Shirasawa S, Augenlicht L. Inhibition of interferon gamma signaling by the short chain fatty acid butyrate. Mol Cancer Res. 2003; 1:855–862. PMID: 14517348.
48. Maslowski KM, Vieira AT, Ng A, Kranich J, Sierro F, Yu D, et al. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature. 2009; 461:1282–1286. PMID: 19865172.
Article
49. Smith PM, Howitt MR, Panikov N, Michaud M, Gallini CA, Bohlooly-Y M, et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science. 2013; 341:569–573. PMID: 23828891.
50. Fukushima Y, Kawata Y, Hara H, Terada A, Mitsuoka T. Effect of a probiotic formula on intestinal immunoglobulin A production in healthy children. Int J Food Microbiol. 1998; 42:39–44. PMID: 9706796.
Article
51. Yasui H, Mike A, Ohwaki M. Immunogenicity of Bifidobacterium breve and change in antibody production in Peyer's patches after oral administration. J Dairy Sci. 1989; 72:30–35. PMID: 2925954.
Article
52. Raes M, Scholtens PA, Alliet P, Hensen K, Jongen H, Boehm G, et al. Exploration of basal immune parameters in healthy infants receiving an infant milk formula supplemented with prebiotics. Pediatr Allergy Immunol. 2010; 21(2 Pt 2):e377–e385. PMID: 20003064.
Article
53. Ben XM, Zhou XY, Zhao WH, Yu WL, Pan W, Zhang WL, et al. Supplementation of milk formula with galacto-oligosaccharides improves intestinal micro-flora and fermentation in term infants. Chin Med J (Engl). 2004; 117:927–931. PMID: 15198901.
54. Muir AB, Benitez AJ, Dods K, Spergel JM, Fillon SA. Microbiome and its impact on gastrointestinal atopy. Allergy. 2016; 71:1256–1263. PMID: 27240281.
Article
55. Aitoro R, Paparo L, Amoroso A, Di Costanzo M, Cosenza L, Granata V, et al. Gut microbiota as a target for preventive and therapeutic intervention against food allergy. Nutrients. 2017; 9:E672. PMID: 28657607.
Article
56. West CE, Renz H, Jenmalm MC, Kozyrskyj AL, Allen KJ, Vuillermin P, et al. in-FLAME Microbiome Interest Group. The gut microbiota and inflammatory noncommunicable diseases: associations and potentials for gut microbiota therapies. J Allergy Clin Immunol. 2015; 135:3–13. quiz 14. PMID: 25567038.
Article
57. Kalliomäki M, Kirjavainen P, Eerola E, Kero P, Salminen S, Isolauri E. Distinct patterns of neonatal gut microflora in infants in whom atopy was and was not developing. J Allergy Clin Immunol. 2001; 107:129–134. PMID: 11150002.
Article
58. Stiemsma LT, Michels KB. The role of the microbiome in the developmental origins of health and disease. Pediatrics. 2018; 141:e20172437. PMID: 29519955.
Article
59. Tang ML, Lahtinen SJ, Boyle RJ. Probiotics and prebiotics: clinical effects in allergic disease. Curr Opin Pediatr. 2010; 22:626–634. PMID: 20733491.
Article
60. Shibata R, Kimura M, Takahashi H, Mikami K, Aiba Y, Takeda H, et al. Clinical effects of kestose, a prebiotic oligosaccharide, on the treatment of atopic dermatitis in infants. Clin Exp Allergy. 2009; 39:1397–1403. PMID: 19508323.
Article
61. Cuello-Garcia CA, Fiocchi A, Pawankar R, Yepes-Nuñez JJ, Morgano GP, Zhang Y, et al. World Allergy Organization-Mcmaster University guidelines for allergic disease prevention (GLAD-P): prebiotics. World Allergy Organ J. 2016; 9:10. PMID: 26962387.
Article
62. Arslanoglu S, Moro GE, Schmitt J, Tandoi L, Rizzardi S, Boehm G. Early dietary intervention with a mixture of prebiotic oligosaccharides reduces the incidence of allergic manifestations and infections during the first two years of life. J Nutr. 2008; 138:1091–1095. PMID: 18492839.
Article
63. Osborn DA, Sinn JK. Prebiotics in infants for prevention of allergy. Cochrane Database Syst Rev. 2013; (3):CD006474. PMID: 23543544.
Article
64. Knol J, Scholtens P, Kafka C, Steenbakkers J, Gro S, Helm K, et al. Colon microflora in infants fed formula with galacto- and fructo-oligosaccharides: more like breast-fed infants. J Pediatr Gastroenterol Nutr. 2005; 40:36–42. PMID: 15625424.
Article
65. Boehm G, Jelinek J, Stahl B, van Laere K, Knol J, Fanaro S, et al. Prebiotics in infant formulas. J Clin Gastroenterol. 2004; 38(6 Suppl):S76–S79. PMID: 15220664.
Article
66. Boehm G, Lidestri M, Casetta P, Jelinek J, Negretti F, Stahl B, et al. Supplementation of a bovine milk formula with an oligosaccharide mixture increases counts of faecal bifidobacteria in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2002; 86:F178–F181. PMID: 11978748.
Article
67. Moro G, Minoli I, Mosca M, Fanaro S, Jelinek J, Stahl B, et al. Dosage-related bifidogenic effects of galacto- and fructooligosaccharides in formula-fed term infants. J Pediatr Gastroenterol Nutr. 2002; 34:291–295. PMID: 11964956.
Article
68. Moreno Villares JM. [Probiotics in infant formulae. Could we modify the immune response?]. An Pediatr (Barc). 2008; 68:286–294. Spanish. PMID: 18358143.
69. Arslanoglu S, Moro GE, Boehm G. Early supplementation of prebiotic oligosaccharides protects formula-fed infants against infections during the first 6 months of life. J Nutr. 2007; 137:2420–2424. PMID: 17951479.
Article
70. Gibson GR. Dietary modulation of the human gut microflora using the prebiotics oligofructose and inulin. J Nutr. 1999; 129(7 Suppl):1438S–1441S. PMID: 10395616.
Article
71. Sartor RB. Therapeutic manipulation of the enteric microflora in inflammatory bowel diseases: antibiotics, probiotics, and prebiotics. Gastroenterology. 2004; 126:1620–1633. PMID: 15168372.
Article
72. Looijer-van Langen MA, Dieleman LA. Prebiotics in chronic intestinal inflammation. Inflamm Bowel Dis. 2009; 15:454–462. PMID: 18831524.
73. de Weerth C, Fuentes S, Puylaert P, de Vos WM. Intestinal microbiota of infants with colic: development and specific signatures. Pediatrics. 2013; 131:e550–8. PMID: 23319531.
Article
74. Dubois NE, Gregory KE. Characterizing the intestinal microbiome in infantile colic: findings based on an integrative review of the literature. Biol Res Nurs. 2016; 18:307–315. PMID: 26721871.
75. Savino F, Cresi F, Maccario S, Cavallo F, Dalmasso P, Fanaro S, et al. “Minor” feeding problems during the first months of life: effect of a partially hydrolysed milk formula containing fructo- and galacto-oligosaccharides. Acta Paediatr Suppl. 2003; 91:86–90. PMID: 14599049.
Article
76. Sherman PM, Cabana M, Gibson GR, Koletzko BV, Neu J, Veereman-Wauters G, et al. Potential roles and clinical utility of prebiotics in newborns, infants, and children: proceedings from a global prebiotic summit meeting, New York City, June 27-28, 2008. J Pediatr. 2009; 155:S61–S70. PMID: 19840609.
Article
77. Schmelzle H, Wirth S, Skopnik H, Radke M, Knol J, Böckler HM, et al. Randomized double-blind study of the nutritional efficacy and bifidogenicity of a new infant formula containing partially hydrolyzed protein, a high beta-palmitic acid level, and nondigestible oligosaccharides. J Pediatr Gastroenterol Nutr. 2003; 36:343–351. PMID: 12604972.
78. Closa-Monasterolo R, Ferré N, Castillejo-DeVillasante G, Luque V, Gispert-Llaurado M, Zaragoza-Jordana M, et al. The use of inulin-type fructans improves stool consistency in constipated children. A randomised clinical trial: pilot study. Int J Food Sci Nutr. 2017; 68:587–594. PMID: 27931142.
Article
79. Ziegler E, Vanderhoof JA, Petschow B, Mitmesser SH, Stolz SI, Harris CL, et al. Term infants fed formula supplemented with selected blends of prebiotics grow normally and have soft stools similar to those reported for breast-fed infants. J Pediatr Gastroenterol Nutr. 2007; 44:359–364. PMID: 17325558.
Article
80. Fanaro S, Marten B, Bagna R, Vigi V, Fabris C, Peña-Quintana L, et al. Galacto-oligosaccharides are bifidogenic and safe at weaning: a double-blind randomized multicenter study. J Pediatr Gastroenterol Nutr. 2009; 48:82–88. PMID: 19172129.
Article
81. Sabater-Molina M, Larqué E, Torrella F, Zamora S. Dietary fructooligosaccharides and potential benefits on health. J Physiol Biochem. 2009; 65:315–328. PMID: 20119826.
Article
82. Koppen IJ, Benninga MA, Tabbers MM. Is there a role for pre-, pro- and synbiotics in the treatment of functional constipation in children? A systematic review. J Pediatr Gastroenterol Nutr. 2016; 63(Suppl 1):S27–S35. PMID: 27380596.
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