Prebiotics: tools to manipulate the gut microbiome and metabolome

Abstract

The human gut is an ecosystem comprising trillions of microbes interacting with the host. The composition of the microbiota and their interactions play roles in different biological processes and in the development of human diseases. Close relationships between dietary modifications, microbiota composition and health status have been established. This review focuses on prebiotics, or compounds which selectively encourage the growth of beneficial bacteria, their mechanisms of action and benefits to human hosts. We also review advances in synthesis technology for human milk oligosaccharides, part of one of the most well-characterized prebiotic–probiotic relationships. Current and future research in this area points to greater use of prebiotics as tools to manipulate the microbial and metabolic diversity of the gut for the benefit of human health.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3

Abbreviations

DP:

Degree of polymerization

HMO:

Human milk oligosaccharide

FOS:

Fructooligosaccharide

GOS:

Galactooligosaccharides

MOS:

Mannan-oligosaccharides

SCFA:

Short-chain fatty acid

XOS:

Xylooligosaccharides

References

  1. 1.

    Aachary AA, Prapulla SG (2011) Xylooligosaccharides (XOS) as an emerging prebiotic: microbial synthesis, utilization, structural characterization, bioactive properties, and applications. Compr Rev Food Sci Food Saf 10:2–16

    CAS  Google Scholar 

  2. 2.

    Akramiene D, Kondrotas A, Didziapetriene J, Kevelaitis E (2007) Effects of beta-glucans on the immune system. Medicina 43:597–606

    PubMed  Google Scholar 

  3. 3.

    Andreas NJ, Kampmann B, Mehring Le-Doare K (2015) Human breast milk: a review on its composition and bioactivity. Early Hum Dev 91:629–635

    CAS  PubMed  Google Scholar 

  4. 4.

    Arora T, Sharma R, Frost G (2011) Propionate. Anti-obesity and satiety enhancing factor? Appetite 56:511–515

    PubMed  Google Scholar 

  5. 5.

    Bäckhed F, Ley RE, Sonnenburg JL, Peterson DA, Gordon JI (2005) Host-bacterial mutualism in the human intestine. Science 307:1915–1920

    PubMed  Google Scholar 

  6. 6.

    Baumgärtner F, Seitz L, Sprenger GA, Albermann C (2013) Construction of Escherichia coli strains with chromosomally integrated expression cassettes for the synthesis of 2′-fucosyllactose. Microb Cell Fact 12:1–13

    Google Scholar 

  7. 7.

    Belenguer A, Duncan SH, Calder AG, Holtrop G, Louis P, Lobley GE, Flint HJ (2006) Two routes of metabolic cross-feeding between Bifidobacterium adolescentis and butyrate-producing anaerobes from the human gut. Appl Environ Microbiol 72:3593–3599

    CAS  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Ben X-M, Zhou X-Y, Zhao W-H, Yu W-L, Pan W, Zhang W-L, Wu S-M, Van Beusekom CM, Schaafsma A (2004) Supplementation of milk formula with galacto-oligosaccharides improves intestinal micro-flora and fermentation in term infants. Chin Med J 117:927–931

    CAS  PubMed  Google Scholar 

  9. 9.

    Bindels LB, Delzenne NM, Cani PD, Walter J (2015) Towards a more comprehensive concept for prebiotics. Nat Rev Gastroenterol Hepatol 12:303–310

    CAS  PubMed  Google Scholar 

  10. 10.

    Bindels LB, Dewulf EM, Delzenne NM (2013) GPR43/FFA2: physiopathological relevance and therapeutic prospects. Trends Pharmacol Sci 34:226–232

    CAS  PubMed  Google Scholar 

  11. 11.

    Birt DF, Boylston T, Hendrich S, Jane J-L, Hollis J, Li L, McClelland J, Moore S, Phillips GJ, Rowling M, Schalinske K, Scott MP, Whitley EM (2013) Resistant starch: promise for improving human health. Adv Nutr 4:587–601

    CAS  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Bode L (2012) Human milk oligosaccharides: every baby needs a sugar mama. Glycobiology 22:1147–1162

    CAS  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Bode L, Contractor N, Barile D, Pohl N, Prudden AR, Boons G-J, Jin Y-S, Jennewein S (2016) Overcoming the limited availability of human milk oligosaccharides: challenges and opportunities for research and application. Nutr Rev 74:635–644

    PubMed  PubMed Central  Google Scholar 

  14. 14.

    Bokulich NA, Chung J, Battaglia T, Henderson N, Jay M, Li H, Lieber AD, Wu F, Perez-Perez GI, Chen Y, Schweizer W, Zheng X, Contreras M, Dominguez-Bello MG, Blaser MJ (2016) Antibiotics, birth mode, and diet shape microbiome maturation during early life. Sci Transl Med 8:343ra82

    PubMed  PubMed Central  Google Scholar 

  15. 15.

    Bravo JA, Forsythe P, Chew MV, Escaravage E, Savignac HM, Dinan TG, Bienenstock J, Cryan JF (2011) Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci USA 108:16050–16055

    CAS  PubMed  Google Scholar 

  16. 16.

    Brown GD (2006) Dectin-1: a signalling non-TLR pattern-recognition receptor. Nat Rev Immunol 6:33–43

    CAS  PubMed  Google Scholar 

  17. 17.

    Brown GD, Gordon S (2001) Immune recognition. A new receptor for beta-glucans. Nature 413:36–37

    CAS  PubMed  Google Scholar 

  18. 18.

    Burokas A, Arboleya S, Moloney RD, Peterson VL, Murphy K, Clarke G, Stanton C, Dinan TG, Cryan JF (2017) Targeting the microbiota-gut-brain axis: prebiotics have anxiolytic and antidepressant-like effects and reverse the impact of chronic stress in mice. Biol Psychiatry 82:472–487

    CAS  PubMed  Google Scholar 

  19. 19.

    Byndloss MX, Olsan EE, Rivera-Chávez F, Tiffany CR, Cevallos SA, Lokken KL, Torres TP, Byndloss AJ, Faber F, Gao Y, Litvak Y, Lopez CA, Xu G, Napoli E, Giulivi C, Tsolis RM, Revzin A, Lebrilla CB, Bäumler AJ (2017) Microbiota-activated PPAR-γ signaling inhibits dysbiotic Enterobacteriaceae expansion. Science 357:570–575

    CAS  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Cani PD (2017) Gut cell metabolism shapes the microbiome. Science 357:548–549

    CAS  PubMed  Google Scholar 

  21. 21.

    Cani PD (2018) Human gut microbiome: hopes, threats and promises. Gut 67:1716–1725

    CAS  PubMed  PubMed Central  Google Scholar 

  22. 22.

    Chang HN, Lee SY, Nielsen J, Stephanopoulos G (2018) Emerging areas in bioengineering. Wiley, Chichester

    Google Scholar 

  23. 23.

    Charbonneau MR, Blanton LV, DiGiulio DB, Relman DA, Lebrilla CB, Mills DA, Gordon JI (2016) A microbial perspective of human developmental biology. Nature 535:48–55

    CAS  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Chaturvedi P, Warren CD, Altaye M, Morrow AL, Ruiz-Palacios G, Pickering LK, Newburg DS (2001) Fucosylated human milk oligosaccharides vary between individuals and over the course of lactation. Glycobiology 11:365–372

    CAS  PubMed  Google Scholar 

  25. 25.

    Chen C, Zhang Y, Xue M, Liu X-W, Li Y, Chen X, Wang PG, Wang F, Cao H (2015) Sequential one-pot multienzyme (OPME) synthesis of lacto-N-neotetraose and its sialyl and fucosyl derivatives. Chem Commun 51:7689–7692

    CAS  Google Scholar 

  26. 26.

    Chen R (2018) Enzyme and microbial technology for synthesis of bioactive oligosaccharides: an update. Appl Microbiol Biotechnol 102:3017–3026

    CAS  PubMed  Google Scholar 

  27. 27.

    Chichlowski M, De Lartigue G, German JB, Raybould HE, Mills DA (2012) Bifidobacteria isolated from infants and cultured on human milk oligosaccharides affect intestinal epithelial function. J Pediatr Gastroenterol Nutr 55:321–327

    CAS  PubMed  PubMed Central  Google Scholar 

  28. 28.

    Chunchai T, Thunapong W, Yasom S, Wanchai K, Eaimworawuthikul S, Metzler G, Lungkaphin A, Pongchaidecha A, Sirilun S, Chaiyasut C, Pratchayasakul W, Thiennimitr P, Chattipakorn N, Chattipakorn SC (2018) Decreased microglial activation through gut-brain axis by prebiotics, probiotics, or synbiotics effectively restored cognitive function in obese-insulin resistant rats. J Neuroinflamm 15:11

    Google Scholar 

  29. 29.

    Chung WSF, Walker AW, Louis P, Parkhill J, Vermeiren J, Bosscher D, Duncan SH, Flint HJ (2016) Modulation of the human gut microbiota by dietary fibres occurs at the species level. BMC Biol 14:3

    PubMed  PubMed Central  Google Scholar 

  30. 30.

    Collins MD, Gibson GR (1999) Probiotics, prebiotics, and synbiotics: approaches for modulating the microbial ecology of the gut. Am J Clin Nutr 69:1052S–1057S

    CAS  PubMed  Google Scholar 

  31. 31.

    Comstock SS, Li M, Wang M, Monaco MH, Kuhlenschmidt TB, Kuhlenschmidt MS, Donovan SM (2017) Dietary human milk oligosaccharides but not prebiotic oligosaccharides increase circulating natural killer cell and mesenteric lymph node memory t cell populations in noninfected and rotavirus-infected neonatal piglets. J Nutr 147:1041–1047

    PubMed  PubMed Central  Google Scholar 

  32. 32.

    Comstock SS, Wang M, Hester SN, Li M, Donovan SM (2014) Select human milk oligosaccharides directly modulate peripheral blood mononuclear cells isolated from 10-d-old pigs. Br J Nutr 111:819–828

    CAS  PubMed  Google Scholar 

  33. 33.

    Costabile A, Kolida S, Klinder A, Gietl E, Bäuerlein M, Frohberg C, Landschütze V, Gibson GR (2010) A double-blind, placebo-controlled, cross-over study to establish the bifidogenic effect of a very-long-chain inulin extracted from globe artichoke (Cynara scolymus) in healthy human subjects. Br J Nutr 104:1007–1017

    CAS  PubMed  Google Scholar 

  34. 34.

    Crout DH, Vic G (1998) Glycosidases and glycosyl transferases in glycoside and oligosaccharide synthesis. Curr Opin Chem Biol 2:98–111

    CAS  PubMed  Google Scholar 

  35. 35.

    David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, Ling AV, Devlin AS, Varma Y, Fischbach MA, Biddinger SB, Dutton RJ, Turnbaugh PJ (2014) Diet rapidly and reproducibly alters the human gut microbiome. Nature 505:559–563

    CAS  PubMed  Google Scholar 

  36. 36.

    Dewulf EM, Cani PD, Claus SP, Fuentes S, Puylaert PGB, Neyrinck AM, Bindels LB, de Vos WM, Gibson GR, Thissen J-P, Delzenne NM (2013) Insight into the prebiotic concept: lessons from an exploratory, double blind intervention study with inulin-type fructans in obese women. Gut 62:1112–1121

    CAS  PubMed  Google Scholar 

  37. 37.

    Drouillard S, Driguez H, Samain E (2006) Large-scale synthesis of H-antigen oligosaccharides by expressing Helicobacter pylori α1,2-fucosyltransferase in metabolically engineered Escherichia coli cells. Angew Chem Int Ed 45:1778–1780

    CAS  Google Scholar 

  38. 38.

    Durrer KE, Allen MS, Hunt von Herbing I (2017) Genetically engineered probiotic for the treatment of phenylketonuria (PKU); assessment of a novel treatment in vitro and in the PAHenu2 mouse model of PKU. PLoS One 12:e0176286

    PubMed  PubMed Central  Google Scholar 

  39. 39.

    El Kaoutari A, Armougom F, Gordon JI, Raoult D, Henrissat B (2013) The abundance and variety of carbohydrate-active enzymes in the human gut microbiota. Nat Rev Microbiol 11:497–504

    PubMed  Google Scholar 

  40. 40.

    Endo T, Koizumi S, Tabata K, Ozaki A (2000) Large-scale production of CMP-NeuAc and sialylated oligosaccharides through bacterial coupling. Appl Microbiol Biotechnol 53:257–261

    CAS  PubMed  Google Scholar 

  41. 41.

    Fair RJ, Hahm HS, Seeberger PH (2015) Combination of automated solid-phase and enzymatic oligosaccharide synthesis provides access to α(2,3)-sialylated glycans. Chem Commun 51:6183–6185

    CAS  Google Scholar 

  42. 42.

    Fanaro S, Marten B, Bagna R, Vigi V, Fabris C, Peña-Quintana L, Argüelles F, Scholz-Ahrens KE, Sawatzki G, Zelenka R, Schrezenmeir J, de Vrese M, Bertino E (2009) Galacto-oligosaccharides are bifidogenic and safe at weaning: a double-blind randomized multicenter study. J Pediatr Gastroenterol Nutr 48:82–88

    CAS  PubMed  Google Scholar 

  43. 43.

    Ferenczi S, Szegi K, Winkler Z, Barna T, Kovács KJ (2016) Oligomannan prebiotic attenuates immunological, clinical and behavioral symptoms in mouse model of inflammatory bowel disease. Sci Rep 6:34132

    CAS  PubMed  PubMed Central  Google Scholar 

  44. 44.

    Fernandes R, do Rosario VA, Mocellin MC, Kuntz MGF, Trindade EBSM (2017) Effects of inulin-type fructans, galacto-oligosaccharides and related synbiotics on inflammatory markers in adult patients with overweight or obesity: a systematic review. Clin Nutr 36:1197–1206

    CAS  PubMed  Google Scholar 

  45. 45.

    Ferreira RM, Pereira-Marques J, Pinto-Ribeiro I, Costa JL, Carneiro F, Machado JC, Figueiredo C (2018) Gastric microbial community profiling reveals a dysbiotic cancer-associated microbiota. Gut 67:226–236

    CAS  PubMed  Google Scholar 

  46. 46.

    Floch MH (2010) Fecal bacteriotherapy, fecal transplant, and the microbiome. J Clin Gastroenterol 44:529–530

    PubMed  Google Scholar 

  47. 47.

    Foster JA, McVey Neufeld K-A (2013) Gut-brain axis: how the microbiome influences anxiety and depression. Trends Neurosci 36:305–312

    CAS  PubMed  Google Scholar 

  48. 48.

    Freeman LR, Haley-Zitlin V, Rosenberger DS, Granholm A-C (2014) Damaging effects of a high-fat diet to the brain and cognition: a review of proposed mechanisms. Nutr Neurosci 17:241–251

    PubMed  Google Scholar 

  49. 49.

    Furusawa Y, Obata Y, Fukuda S, Endo TA, Nakato G, Takahashi D, Nakanishi Y, Uetake C, Kato K, Kato T, Takahashi M, Fukuda NN, Murakami S, Miyauchi E, Hino S, Atarashi K, Onawa S, Fujimura Y, Lockett T, Clarke JM, Topping DL, Tomita M, Hori S, Ohara O, Morita T, Koseki H, Kikuchi J, Honda K, Hase K, Ohno H (2013) Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504:446–450

    CAS  Google Scholar 

  50. 50.

    Gibson GR, Hutkins R, Sanders ME, Prescott SL, Reimer RA, Salminen SJ, Scott K, Stanton C, Swanson KS, Cani PD, Verbeke K, Reid G (2017) 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 14:491–502

    PubMed  Google Scholar 

  51. 51.

    Gibson GR, Probert HM, Loo JV, Rastall RA, Roberfroid MB (2004) Dietary modulation of the human colonic microbiota: updating the concept of prebiotics. Nutr Res Rev 17:259–275

    CAS  PubMed  Google Scholar 

  52. 52.

    Gibson GR, Rastall RA (2006) Prebiotics: development & application. Wiley, Chichester

    Google Scholar 

  53. 53.

    Gibson GR, Roberfroid MB (1995) Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. J Nutr 125:1401–1412

    CAS  PubMed  Google Scholar 

  54. 54.

    Gill SR, Pop M, Deboy RT, Eckburg PB, Turnbaugh PJ, Samuel BS, Gordon JI, Relman DA, Fraser-Liggett CM, Nelson KE (2006) Metagenomic analysis of the human distal gut microbiome. Science 312:1355–1359

    CAS  PubMed  PubMed Central  Google Scholar 

  55. 55.

    Grulee CG, Sanford HN, Herron PH (1934) Breast and artificial feeding: influence on morbidity and mortality of twenty thousand infants. JAMA 103:735–739

    Google Scholar 

  56. 56.

    Guo L, Chen X, Xu L, Xiao M, Lu L (2018) Enzymatic synthesis of 6′-sialyllactose, a dominant sialylated human milk oligosaccharide, by a novel exo-α-sialidase from Bacteroides fragilis NCTC9343. Appl Environ Microbiol. https://doi.org/10.1128/aem.00071-18

    Article  PubMed  PubMed Central  Google Scholar 

  57. 57.

    Gyorgy P, Norris RF, Rose CS (1954) Bifidus factor. I. A variant of Lactobacillus bifidus requiring a special growth factor. Arch Biochem Biophys 48:193–201

    CAS  PubMed  Google Scholar 

  58. 58.

    Haberman Y, Tickle TL, Dexheimer PJ, Kim M-O, Tang D, Karns R, Baldassano RN, Noe JD, Rosh J, Markowitz J, Heyman MB, Griffiths AM, Crandall WV, Mack DR, Baker SS, Huttenhower C, Keljo DJ, Hyams JS, Kugathasan S, Walters TD, Aronow B, Xavier RJ, Gevers D, Denson LA (2014) Pediatric Crohn disease patients exhibit specific ileal transcriptome and microbiome signature. J Clin Invest 124:3617–3633

    CAS  PubMed  PubMed Central  Google Scholar 

  59. 59.

    Hansen CHF, Frøkiær H, Christensen AG, Bergström A, Licht TR, Hansen AK, Metzdorff SB (2013) Dietary xylooligosaccharide downregulates IFN-γ and the low-grade inflammatory cytokine IL-1β systemically in mice. J Nutr 143:533–540

    CAS  PubMed  Google Scholar 

  60. 60.

    Hardy H, Harris J, Lyon E, Beal J, Foey AD (2013) Probiotics, prebiotics and immunomodulation of gut mucosal defences: homeostasis and immunopathology. Nutrients 5:1869–1912

    CAS  PubMed  PubMed Central  Google Scholar 

  61. 61.

    Herrmann GF, Elling L, Krezdorn CH, Kleene R, Berger EG, Wandrey C (1995) Use of transformed whole yeast cells expressing β-1,4-galactosyltransferase for the synthesis of N-acetyllactosamine. Bioorg Med Chem Lett 5:673–676

    CAS  Google Scholar 

  62. 62.

    Herrmann GF, Wang P, Shen G-J, Wong C-H (1994) Recombinant whole cells as catalysts for the enzymatic synthesis of oligosaccharides and glycopeptides. Angew Chem Int Ed Engl 33:1241–1242

    Google Scholar 

  63. 63.

    Hoentjen F, Welling GW, Harmsen HJM, Zhang X, Snart J, Tannock GW, Lien K, Churchill TA, Lupicki M, Dieleman LA (2005) Reduction of colitis by prebiotics in HLA-B27 transgenic rats is associated with microflora changes and immunomodulation. Inflamm Bowel Dis 11:977–985

    PubMed  Google Scholar 

  64. 64.

    Hosono A, Ozawa A, Kato R, Ohnishi Y, Nakanishi Y, Kimura T, Nakamura R (2003) Dietary fructooligosaccharides induce immunoregulation of intestinal IgA secretion by murine Peyer’s patch cells. Biosci Biotechnol Biochem 67:758–764

    CAS  PubMed  Google Scholar 

  65. 65.

    Howard MD, Gordon DT, Garleb KA, Kerley MS (1995) Dietary fructooligosaccharide, xylooligosaccharide and gum arabic have variable effects on cecal and colonic microbiota and epithelial cell proliferation in mice and rats. J Nutr 125:2604–2609

    CAS  PubMed  Google Scholar 

  66. 66.

    Hsu C-K, Liao J-W, Chung Y-C, Hsieh C-P, Chan Y-C (2004) Xylooligosaccharides and fructooligosaccharides affect the intestinal microbiota and precancerous colonic lesion development in rats. J Nutr 134:1523–1528

    CAS  PubMed  Google Scholar 

  67. 67.

    Isabella VM, Ha BN, Castillo MJ, Lubkowicz DJ, Rowe SE, Millet YA, Anderson CL, Li N, Fisher AB, West KA, Reeder PJ, Momin MM, Bergeron CG, Guilmain SE, Miller PF, Kurtz CB, Falb D (2018) Development of a synthetic live bacterial therapeutic for the human metabolic disease phenylketonuria. Nat Biotechnol 36:857–864

    CAS  PubMed  Google Scholar 

  68. 68.

    Kassam Z, Hundal R, Marshall JK, Lee CH (2012) Fecal transplant via retention enema for refractory or recurrent Clostridium difficile infection. Arch Intern Med 172:191–193

    PubMed  Google Scholar 

  69. 69.

    Bych K, Miks MH, Johanson T, Hederos MJ, Vigsnaes LK, Becker P (2018) Production of HMOs using microbial hosts—from cell engineering to large scale production. Curr Opin Biotechnol 56:130–137

    PubMed  Google Scholar 

  70. 70.

    Kearney SM, Gibbons SM, Erdman SE, Alm EJ (2018) Orthogonal dietary niche enables reversible engraftment of a gut bacterial commensal. Cell Rep 24:1842–1851

    CAS  PubMed  PubMed Central  Google Scholar 

  71. 71.

    Kim G-B, Seo YM, Kim CH, Paik IK (2011) Effect of dietary prebiotic supplementation on the performance, intestinal microflora, and immune response of broilers. Poult Sci 90:75–82

    CAS  PubMed  Google Scholar 

  72. 72.

    King A (2012) Prevention. Cost-effectiveness of cardiovascular disease prevention and management in the developing world. Nat Rev Cardiol 9:258

    PubMed  Google Scholar 

  73. 73.

    Klinder A, Forster A, Caderni G, Femia AP, Pool-Zobel BL (2004) Fecal water genotoxicity is predictive of tumor-preventive activities by inulin-like oligofructoses, probiotics (Lactobacillus rhamnosus and Bifidobacterium lactis), and their synbiotic combination. Nutr Cancer 49:144–155

    CAS  PubMed  Google Scholar 

  74. 74.

    Kobayashi T, Okazaki M, Fujikawa S, Koga K (1991) Effect of xylooligosaccharides on feces of men. J Jpn Soc Biosci Biotech Agrochem 65:1651–1653

    CAS  Google Scholar 

  75. 75.

    Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, Britt EB, Fu X, Wu Y, Li L, Smith JD, DiDonato JA, Chen J, Li H, Wu GD, Lewis JD, Warrier M, Brown JM, Krauss RM, Tang WHW, Bushman FD, Lusis AJ, Hazen SL (2013) Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med 19:576–585

    CAS  PubMed  PubMed Central  Google Scholar 

  76. 76.

    Kontula P, von Wright A, Mattila-Sandholm T (1998) Oat bran β-gluco- and xylo-oligosaccharides as fermentative substrates for lactic acid bacteria. Int J Food Microbiol 45:163–169

    CAS  PubMed  Google Scholar 

  77. 77.

    Kostic AD, Xavier RJ, Gevers D (2014) The microbiome in inflammatory bowel disease: current status and the future ahead. Gastroenterology 146:1489–1499

    CAS  PubMed  PubMed Central  Google Scholar 

  78. 78.

    Kunz C, Rudloff S, Baier W, Klein N, Strobel S (2000) Oligosaccharides in human milk: structural, functional, and metabolic aspects. Annu Rev Nutr 20:699–722

    CAS  PubMed  Google Scholar 

  79. 79.

    Kurtz CB, Millet YA, Puurunen MK, Perreault M, Charbonneau MR, Isabella VM, Kotula JW, Antipov E, Dagon Y, Denney WS, Wagner DA, West KA, Degar AJ, Brennan AM, Miller PF (2019) An engineered E. coli Nissle improves hyperammonemia and survival in mice and shows dose-dependent exposure in healthy humans. Sci Transl Med. https://doi.org/10.1126/scitranslmed.aau7975

    Article  PubMed  Google Scholar 

  80. 80.

    Kurtz C, Denney WS, Blankstein L, Guilmain SE, Machinani S, Kotula J, Saha S, Miller P, Brennan AM (2018) Translational development of microbiome-based therapeutics: kinetics of E. coli Nissle and engineered strains in humans and nonhuman primates. Clin Transl Sci 11:200–207

    CAS  PubMed  Google Scholar 

  81. 81.

    Lee W-H, Pathanibul P, Quarterman J, Jo J-H, Han NS, Miller MJ, Jin Y-S, Seo J-H (2012) Whole cell biosynthesis of a functional oligosaccharide, 2′-fucosyllactose, using engineered Escherichia coli. Microb Cell Fact 11:1–9

    Google Scholar 

  82. 82.

    Lewandowska U, Szewczyk K, Hrabec E, Janecka A, Gorlach S (2013) Overview of metabolism and bioavailability enhancement of polyphenols. J Agric Food Chem 61:12183–12199

    CAS  PubMed  Google Scholar 

  83. 83.

    Lewis S, Burmeister S, Brazier J (2005) Effect of the Prebiotic oligofructose on relapse of Clostridium difficile-associated diarrhea: a randomized, controlled study. Clin Gastroenterol Hepatol 3:442–448

    CAS  PubMed  Google Scholar 

  84. 84.

    Ley RE, Bäckhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI (2005) Obesity alters gut microbial ecology. Proc Natl Acad Sci USA 102:11070–11075

    CAS  PubMed  Google Scholar 

  85. 85.

    Liu RH (2004) Potential synergy of phytochemicals in cancer prevention: mechanism of action. J Nutr 134:3479S–3485S

    CAS  PubMed  Google Scholar 

  86. 86.

    Makki K, Deehan EC, Walter J, Bäckhed F (2018) The impact of dietary fiber on gut microbiota in host health and disease. Cell Host Microbe 23:705–715

    CAS  PubMed  Google Scholar 

  87. 87.

    Manthey CF, Autran CA, Eckmann L, Bode L (2014) Human milk oligosaccharides protect against enteropathogenic Escherichia coli attachment in vitro and EPEC colonization in suckling mice. J Pediatr Gastroenterol Nutr 58:165–168

    PubMed  Google Scholar 

  88. 88.

    Marcobal A, Barboza M, Sonnenburg ED, Pudlo N, Martens EC, Desai P, Lebrilla CB, Weimer BC, Mills DA, German JB, Sonnenburg JL (2011) Bacteroides in the infant gut consume milk oligosaccharides via mucus-utilization pathways. Cell Host Microbe 10:507–514

    CAS  PubMed  PubMed Central  Google Scholar 

  89. 89.

    Mariño E, Richards JL, McLeod KH, Stanley D, Yap YA, Knight J, McKenzie C, Kranich J, Oliveira AC, Rossello FJ, Krishnamurthy B, Nefzger CM, Macia L, Thorburn A, Baxter AG, Morahan G, Wong LH, Polo JM, Moore RJ, Lockett TJ, Clarke JM, Topping DL, Harrison LC, Mackay CR (2017) Gut microbial metabolites limit the frequency of autoimmune T cells and protect against type 1 diabetes. Nat Immunol 18:552–562

    PubMed  Google Scholar 

  90. 90.

    Martens EC, Koropatkin NM, Smith TJ, Gordon JI (2009) Complex glycan catabolism by the human gut microbiota: the Bacteroidetes Sus-like paradigm. J Biol Chem 284:24673–24677

    CAS  PubMed  PubMed Central  Google Scholar 

  91. 91.

    McNulty NP, Wu M, Erickson AR, Pan C, Erickson BK, Martens EC, Pudlo NA, Muegge BD, Henrissat B, Hettich RL, Gordon JI (2013) Effects of diet on resource utilization by a model human gut microbiota containing Bacteroides cellulosilyticus WH2, a symbiont with an extensive glycobiome. PLoS Biol 11:e1001637

    CAS  PubMed  PubMed Central  Google Scholar 

  92. 92.

    Miene C, Weise A, Glei M (2011) Impact of polyphenol metabolites produced by colonic microbiota on expression of COX-2 and GSTT2 in human colon cells (LT97). Nutr Cancer 63:653–662

    CAS  PubMed  Google Scholar 

  93. 93.

    Miller TL, Wolin MJ (1996) Pathways of acetate, propionate, and butyrate formation by the human fecal microbial flora. Appl Environ Microbiol 62:1589–1592

    CAS  PubMed  PubMed Central  Google Scholar 

  94. 94.

    Momeni-Moghaddam P, Keyvanshokooh S, Ziaei-Nejad S, Parviz Salati A, Pasha-Zanoosi H (2015) Effects of mannan oligosaccharide supplementation on growth, some immune responses and gut lactic acid bacteria of common carp (Cyprinus Carpio) fingerlings. Vet Res Forum 6:239–244

    PubMed  PubMed Central  Google Scholar 

  95. 95.

    Moro G, Arslanoglu S, Stahl B, Jelinek J, Wahn U, Boehm G (2006) A mixture of prebiotic oligosaccharides reduces the incidence of atopic dermatitis during the first six months of age. Arch Dis Child 91:814–819

    CAS  PubMed  PubMed Central  Google Scholar 

  96. 96.

    Muegge BD, Kuczynski J, Knights D, Clemente JC, González A, Fontana L, Henrissat B, Knight R, Gordon JI (2011) Diet drives convergence in gut microbiome functions across mammalian phylogeny and within humans. Science 332:970–974

    CAS  PubMed  PubMed Central  Google Scholar 

  97. 97.

    Musso G, Gambino R, Cassader M (2010) Gut microbiota as a regulator of energy homeostasis and ectopic fat deposition: mechanisms and implications for metabolic disorders. Curr Opin Lipidol 21:76–83

    CAS  PubMed  Google Scholar 

  98. 98.

    Nagura T, Hachimura S, Hashiguchi M, Ueda Y, Kanno T, Kikuchi H, Sayama K, Kaminogawa S (2002) Suppressive effect of dietary raffinose on T-helper 2 cell-mediated immunity. Br J Nutr 88:421–426

    CAS  PubMed  Google Scholar 

  99. 99.

    Newburg DS, Walker WA (2007) Protection of the neonate by the innate immune system of developing gut and of human milk. Pediatr Res 61:2–8

    CAS  PubMed  Google Scholar 

  100. 100.

    Niness KR (1999) Inulin and oligofructose: what are they? J Nutr 129:1402S–1406S

    CAS  PubMed  Google Scholar 

  101. 101.

    Obermeier S, Rudloff S, Pohlentz G, Lentze MJ, Kunz C (1999) Secretion of 13C-labelled oligosaccharides into human milk and infant’s urine after an oral [13C]galactose load. Isotopes Environ Health Stud 35:119–125

    CAS  PubMed  Google Scholar 

  102. 102.

    Ofek I, Beachey EH (1978) Mannose binding and epithelial cell adherence of Escherichia coli. Infect Immunity 22:247–254

    CAS  Google Scholar 

  103. 103.

    Okazaki M, Fujikawa S, Matsumoto N (1990) Effect of xylooligosaccharide on the growth of bifidobacteria. Bifidobact Microflora 9:77–86

    Google Scholar 

  104. 104.

    Osman N, Adawi D, Molin G, Ahrne S, Berggren A, Jeppsson B (2006) Bifidobacterium infantis strains with and without a combination of oligofructose and inulin (OFI) attenuate inflammation in DSS-induced colitis in rats. BMC Gastroenterol 6:31

    PubMed  PubMed Central  Google Scholar 

  105. 105.

    Paineau D, Payen F, Panserieu S, Coulombier G, Sobaszek A, Lartigau I, Brabet M, Galmiche J-P, Tripodi D, Sacher-Huvelin S, Chapalain V, Zourabichvili O, Respondek F, Wagner A, Bornet FRJ (2008) The effects of regular consumption of short-chain fructo-oligosaccharides on digestive comfort of subjects with minor functional bowel disorders. Br J Nutr 99:311–318

    CAS  PubMed  Google Scholar 

  106. 106.

    Pant K, Yadav AK, Gupta P, Islam R, Saraya A, Venugopal SK (2017) Butyrate induces ROS-mediated apoptosis by modulating miR-22/SIRT-1 pathway in hepatic cancer cells. Redox Biol 12:340–349

    CAS  PubMed  PubMed Central  Google Scholar 

  107. 107.

    Parnell JA, Reimer RA (2010) Effect of prebiotic fibre supplementation on hepatic gene expression and serum lipids: a dose-response study in JCR:LA-cp rats. Br J Nutr 103:1577–1584

    CAS  PubMed  Google Scholar 

  108. 108.

    Pereira FC, Berry D (2017) Microbial nutrient niches in the gut. Environ Microbiol 19:1366–1378

    PubMed  PubMed Central  Google Scholar 

  109. 109.

    Perugino G, Trincone A, Rossi M, Moracci M (2004) Oligosaccharide synthesis by glycosynthases. Trends Biotechnol 22:31–37

    CAS  PubMed  Google Scholar 

  110. 110.

    Phelps CF (1965) The physical properties of inulin solutions. Biochem J 95:41–47

    CAS  PubMed  PubMed Central  Google Scholar 

  111. 111.

    Plante OJ, Palmacci ER, Seeberger PH (2001) Automated solid-phase synthesis of oligosaccharides. Science 291:1523–1527

    CAS  PubMed  Google Scholar 

  112. 112.

    Pourghassem Gargari B, Dehghan P, Aliasgharzadeh A, Asghari Jafar-Abadi M (2013) Effects of high performance inulin supplementation on glycemic control and antioxidant status in women with type 2 diabetes. Diabetes Metab J 37:140–148

    PubMed  PubMed Central  Google Scholar 

  113. 113.

    Priem B, Gilbert M, Wakarchuk WW, Heyraud A, Samain E (2002) A new fermentation process allows large-scale production of human milk oligosaccharides by metabolically engineered bacteria. Glycobiology 12:235–240

    CAS  PubMed  Google Scholar 

  114. 114.

    Propst EL, Flickinger EA, Bauer LL, Merchen NR, Fahey GC Jr (2003) A dose-response experiment evaluating the effects of oligofructose and inulin on nutrient digestibility, stool quality, and fecal protein catabolites in healthy adult dogs. J Anim Sci 81:3057–3066

    CAS  PubMed  Google Scholar 

  115. 115.

    Prudden AR, Chinoy ZS, Wolfert MA, Boons G-J (2014) A multifunctional anomeric linker for the chemoenzymatic synthesis of complex oligosaccharides. Chem Commun 50:7132–7135

    CAS  Google Scholar 

  116. 116.

    Quintero M, Maldonado M, Perez-Munoz M, Jimenez R, Fangman T, Rupnow J, Wittke A, Russell M, Hutkins R (2011) Adherence inhibition of Cronobacter sakazakii to intestinal epithelial cells by prebiotic oligosaccharides. Curr Microbiol 62:1448–1454

    CAS  PubMed  Google Scholar 

  117. 117.

    Rastall RA, Gibson GR (2015) Recent developments in prebiotics to selectively impact beneficial microbes and promote intestinal health. Curr Opin Biotechnol 32:42–46

    CAS  PubMed  Google Scholar 

  118. 118.

    dos Reis SA, da Conceição LL, Rosa DD, Dias MMDS, Peluzio MDCG (2014) Mechanisms used by inulin-type fructans to improve the lipid profile. Nutr Hosp 31:528–534

    PubMed  Google Scholar 

  119. 119.

    Roberfroid MB (2005) Introducing inulin-type fructans. Br J Nutr 93:S13–S25

    CAS  PubMed  Google Scholar 

  120. 120.

    Rogler G, Andus T (1998) Cytokines in inflammatory bowel disease. World J Surg 22:382–389

    CAS  PubMed  Google Scholar 

  121. 121.

    Roller M, Rechkemmer G, Watzl B (2004) Prebiotic inulin enriched with oligofructose in combination with the probiotics Lactobacillus rhamnosus and Bifidobacterium lactis modulates intestinal immune functions in rats. J Nutr 134:153–156

    CAS  PubMed  Google Scholar 

  122. 122.

    Ross GD, Větvička V (2008) CR122 (CD11b, CD18): a phagocyte and NK cell membrane receptor with multiple ligand specificities and functions. Clin Exp Immunol 92:181–184

    Google Scholar 

  123. 123.

    Rowland IR, Rumney CJ, Coutts JT, Lievense LC (1998) Effect of Bifidobacterium longum and inulin on gut bacterial metabolism and carcinogen-induced aberrant crypt foci in rats. Carcinogenesis 19:281–285

    CAS  PubMed  Google Scholar 

  124. 124.

    Ruffing A, Mao Z, Ruizhen Chen R (2006) Metabolic engineering of Agrobacterium sp. for UDP-galactose regeneration and oligosaccharide synthesis. Metab Eng 8:465–473

    CAS  PubMed  Google Scholar 

  125. 125.

    Ruiz-Palacios GM, Cervantes LE, Ramos P, Chavez-Munguia B, Newburg DS (2003) Campylobacter jejuni binds intestinal H(O) antigen (Fucα1, 2Galβ1, 4GlcNAc), and fucosyloligosaccharides of human milk inhibit its binding and infection. J Biol Chem 278:14112–14120

    CAS  PubMed  Google Scholar 

  126. 126.

    Salyers AA, Vercellotti JR, West SE, Wilkins TD (1977) Fermentation of mucin and plant polysaccharides by strains of Bacteroides from the human colon. Appl Environ Microbiol 33:319–322

    CAS  PubMed  PubMed Central  Google Scholar 

  127. 127.

    Salyers AA, West SE, Vercellotti JR, Wilkins TD (1977) Fermentation of mucins and plant polysaccharides by anaerobic bacteria from the human colon. Appl Environ Microbiol 34:529–533

    CAS  PubMed  PubMed Central  Google Scholar 

  128. 128.

    Saville BA, Saville S (2018) Xylooligosaccharides and arabinoxylanoligosaccharides and their application as prebiotics. Appl Food Biotechnol 5:121–130

    CAS  Google Scholar 

  129. 129.

    Scholz-Ahrens KE, Schaafsma G, van den Heuvel EG, Schrezenmeir J (2001) Effects of prebiotics on mineral metabolism. Am J Clin Nutr 73:459S–464S

    CAS  PubMed  Google Scholar 

  130. 130.

    Schuster M, Wang P, Paulson JC, Wong C-H (1994) Solid-Phase Chemical-Enzymic Synthesis of Glycopeptides and Oligosaccharides. J Am Chem Soc 116:1135–1136

    CAS  Google Scholar 

  131. 131.

    Sears P, Wong CH (2001) Toward automated synthesis of oligosaccharides and glycoproteins. Science 291:2344–2350

    CAS  PubMed  Google Scholar 

  132. 132.

    Sender R, Fuchs S, Milo R (2016) Revised estimates for the number of human and bacteria cells in the body. PLoS Biol 14:e1002533

    PubMed  PubMed Central  Google Scholar 

  133. 133.

    Sender R, Fuchs S, Milo R (2016) Are we really vastly outnumbered? Revisiting the ratio of bacterial to host cells in humans. Cell 164:337–340

    CAS  PubMed  Google Scholar 

  134. 134.

    Shepherd ES, DeLoache WC, Pruss KM, Whitaker WR, Sonnenburg JL (2018) An exclusive metabolic niche enables strain engraftment in the gut microbiota. Nature 557:434–438

    CAS  PubMed  PubMed Central  Google Scholar 

  135. 135.

    Sierra C, Bernal M-J, Blasco J, Martínez R, Dalmau J, Ortuño I, Espín B, Vasallo M-I, Gil D, Vidal M-L, Infante D, Leis R, Maldonado J, Moreno J-M, Román E (2015) 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 54:89–99

    CAS  PubMed  Google Scholar 

  136. 136.

    Silk DBA, Davis A, Vulevic J, Tzortzis G, Gibson GR (2009) Clinical trial: the effects of a trans-galactooligosaccharide prebiotic on faecal microbiota and symptoms in irritable bowel syndrome. Aliment Pharmacol Ther 29:508–518

    CAS  PubMed  Google Scholar 

  137. 137.

    Smiricky-Tjardes MR, Flickinger EA, Grieshop CM, Bauer LL, Murphy MR, Fahey GC Jr (2003) In vitro fermentation characteristics of selected oligosaccharides by swine fecal microflora. J Anim Sci 81:2505–2514

    CAS  PubMed  Google Scholar 

  138. 138.

    Smith PM, Howitt MR, Panikov N, Michaud M, Gallini CA, Bohlooly-Y M, Glickman JN, Garrett WS (2013) The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 341:569–573

    CAS  Google Scholar 

  139. 139.

    Stewart ML, Timm DA, Slavin JL (2008) Fructooligosaccharides exhibit more rapid fermentation than long-chain inulin in an in vitro fermentation system. Nutr Res 28:329–334

    CAS  PubMed  Google Scholar 

  140. 140.

    Tang WHW, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, Wu Y, Hazen SL (2013) Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med 368:1575–1584

    CAS  PubMed  PubMed Central  Google Scholar 

  141. 141.

    Tan J, McKenzie C, Vuillermin PJ, Goverse G, Vinuesa CG, Mebius RE, Macia L, Mackay CR (2016) Dietary fiber and bacterial SCFA enhance oral tolerance and protect against food allergy through diverse cellular pathways. Cell Rep 15:2809–2824

    CAS  PubMed  Google Scholar 

  142. 142.

    Thilakarathna WW, Langille MGI, Rupasinghe HPV (2018) Polyphenol-based prebiotics and synbiotics: potential for cancer chemoprevention. Curr Opin Food Sci 20:51–57

    Google Scholar 

  143. 143.

    Thompson WG, Longstreth GF, Drossman DA, Heaton KW, Irvine EJ, Müller-Lissner SA (1999) Functional bowel disorders and functional abdominal pain. Gut 45:II43–II47

    PubMed  PubMed Central  Google Scholar 

  144. 144.

    Thongaram T, Hoeflinger JL, Chow J, Miller MJ (2017) Prebiotic galactooligosaccharide metabolism by probiotic lactobacilli and bifidobacteria. J Agric Food Chem 65:4184–4192

    CAS  PubMed  Google Scholar 

  145. 145.

    Tilg H, Adolph TE, Gerner RR, Moschen AR (2018) The intestinal microbiota in colorectal cancer. Cancer Cell 33:954–964

    CAS  PubMed  Google Scholar 

  146. 146.

    Tomás-Barberán FA, Selma MV, Espín JC (2016) Interactions of gut microbiota with dietary polyphenols and consequences to human health. Curr Opin Clin Nutr Metab Care 19:471–476

    PubMed  Google Scholar 

  147. 147.

    Trautwein EA, Rieckhoff D, Erbersdobler HF (1998) Dietary inulin lowers plasma cholesterol and triacylglycerol and alters biliary bile acid profile in hamsters. J Nutr 128:1937–1943

    CAS  PubMed  Google Scholar 

  148. 148.

    Treves DS, Manning S, Adams J (1998) Repeated evolution of an acetate-crossfeeding polymorphism in long-term populations of Escherichia coli. Mol Biol Evol 15:789–797

    CAS  PubMed  Google Scholar 

  149. 149.

    Tuohy KM, Probert HM, Smejkal CW, Gibson GR (2003) Using probiotics and prebiotics to improve gut health. Drug Discov Today 8:692–700

    PubMed  Google Scholar 

  150. 150.

    Turnbaugh PJ, Bäckhed F, Fulton L, Gordon JI (2008) Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe 3:213–223

    CAS  Google Scholar 

  151. 151.

    Turroni F, Milani C, Duranti S, Mahony J, van Sinderen D, Ventura M (2018) Glycan utilization and cross-feeding activities by bifidobacteria. Trends Microbiol 26:339–350

    CAS  PubMed  Google Scholar 

  152. 152.

    Tzortzis G, Vulevic J (2009) Galacto-oligosaccharide prebiotics. In: Charalampopoulos D, Rastall RA (eds) Prebiotics and probiotics science and technology. Springer, New York, pp 207–244

    Google Scholar 

  153. 153.

    Underwood MA, Gaerlan S, De Leoz MLA, Dimapasoc L, Kalanetra KM, Lemay DG, German JB, Mills DA, Lebrilla CB (2015) Human milk oligosaccharides in premature infants: absorption, excretion, and influence on the intestinal microbiota. Pediatr Res 78:670–677

    CAS  PubMed  PubMed Central  Google Scholar 

  154. 154.

    Underwood MA, German JB, Lebrilla CB, Mills DA (2015) Bifidobacterium longum subspecies infantis: champion colonizer of the infant gut. Pediatr Res 77:229–235

    CAS  PubMed  Google Scholar 

  155. 155.

    Vandeputte D, Falony G, Vieira-Silva S, Wang J, Sailer M, Theis S, Verbeke K, Raes J (2017) Prebiotic inulin-type fructans induce specific changes in the human gut microbiota. Gut 66:1968–1974

    CAS  PubMed  PubMed Central  Google Scholar 

  156. 156.

    Vatanen T, Franzosa EA, Schwager R, Tripathi S, Arthur TD, Vehik K, Lernmark Å, Hagopian WA, Rewers MJ, She J-X, Toppari J, Ziegler A-G, Akolkar B, Krischer JP, Stewart CJ, Ajami NJ, Petrosino JF, Gevers D, Lähdesmäki H, Vlamakis H, Huttenhower C, Xavier RJ (2018) The human gut microbiome in early-onset type 1 diabetes from the TEDDY study. Nature 562:589–594

    CAS  Google Scholar 

  157. 157.

    Vinolo MAR, Rodrigues HG, Nachbar RT, Curi R (2011) Regulation of inflammation by short chain fatty acids. Nutrients 3:858–876

    CAS  PubMed  PubMed Central  Google Scholar 

  158. 158.

    Vogt L, Meyer D, Pullens G, Faas M, Smelt M, Venema K, Ramasamy U, Schols HA, De Vos P (2015) Immunological properties of inulin-type fructans. Crit Rev Food Sci Nutr 55:414–436

    CAS  PubMed  Google Scholar 

  159. 159.

    Vohra Y, Vasan M, Venot A, Boons G-J (2008) One-pot synthesis of oligosaccharides by combining reductive openings of benzylidene acetals and glycosylations. Org Lett 10:3247–3250

    CAS  PubMed  PubMed Central  Google Scholar 

  160. 160.

    Vulevic J, Drakoularakou A, Yaqoob P, Tzortzis G, Gibson GR (2008) Modulation of the fecal microflora profile and immune function by a novel trans-galactooligosaccharide mixture (B-GOS) in healthy elderly volunteers. Am J Clin Nutr 88:1438–1446

    CAS  PubMed  Google Scholar 

  161. 161.

    Waldecker M, Kautenburger T, Daumann H, Busch C, Schrenk D (2008) Inhibition of histone-deacetylase activity by short-chain fatty acids and some polyphenol metabolites formed in the colon. J Nutr Biochem 19:587–593

    CAS  PubMed  Google Scholar 

  162. 162.

    Wang C-C, Lee J-C, Luo S-Y, Kulkarni SS, Huang Y-W, Lee C-C, Chang K-L, Hung S-C (2007) Regioselective one-pot protection of carbohydrates. Nature 446:896–899

    CAS  PubMed  Google Scholar 

  163. 163.

    Weng M, Ganguli K, Zhu W, Shi HN, Walker WA (2014) Conditioned medium from Bifidobacterium infantis protects against Cronobacter sakazakii-induced intestinal inflammation in newborn mice. Am J Physiol Gastrointest Liver Physiol 306:G779–G787

    CAS  PubMed  PubMed Central  Google Scholar 

  164. 164.

    Whistler RL, Bushway AA, Singh PP, Nakahara W, Tokuzen R (1976) Noncytotoxic, antitumor polysaccharides. In: Tipson RS (ed) Advances in carbohydrate chemistry and biochemistry. Academic Press, Cambridge, pp 235–275

    Google Scholar 

  165. 165.

    White BA, Lamed R, Bayer EA, Flint HJ (2014) Biomass utilization by gut microbiomes. Annu Rev Microbiol 68:279–296

    CAS  PubMed  Google Scholar 

  166. 166.

    Xiao L, Van’t Land B, Engen PA, Naqib A, Green SJ, Nato A, Leusink-Muis T, Garssen J, Keshavarzian A, Stahl B, Folkerts G (2018) Human milk oligosaccharides protect against the development of autoimmune diabetes in NOD-mice. Sci Rep 8:3829

    PubMed  PubMed Central  Google Scholar 

  167. 167.

    Yamashita K, Kawai K, Itakura M (1984) Effects of fructo-oligosaccharides on blood glucose and serum lipids in diabetic subjects. Nutr Res 4:961–966

    CAS  Google Scholar 

  168. 168.

    Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG, Contreras M, Magris M, Hidalgo G, Baldassano RN, Anokhin AP, Heath AC, Warner B, Reeder J, Kuczynski J, Caporaso JG, Lozupone CA, Lauber C, Clemente JC, Knights D, Knight R, Gordon JI (2012) Human gut microbiome viewed across age and geography. Nature 486:222–227

    CAS  PubMed  PubMed Central  Google Scholar 

  169. 169.

    Yu J, Shin J, Park M, Seydametova E, Jung S-M, Seo J-H, Kweon D-H (2018) Engineering of α-1,3-fucosyltransferases for production of 3-fucosyllactose in Escherichia coli. Metab Eng 48:269–278

    CAS  PubMed  Google Scholar 

  170. 170.

    Yu S, Liu J-J, Yun EJ, Kwak S, Kim KH, Jin Y-S (2018) Production of a human milk oligosaccharide 2′-fucosyllactose by metabolically engineered Saccharomyces cerevisiae. Microb Cell Fact 17:101

    PubMed  PubMed Central  Google Scholar 

  171. 171.

    Yu Y, Lasanajak Y, Song X, Hu L, Ramani S, Mickum ML, Ashline DJ, Prasad BVV, Estes MK, Reinhold VN, Cummings RD, Smith DF (2014) Human milk contains novel glycans that are potential decoy receptors for neonatal rotaviruses. Mol Cell Proteom 13:2944–2960

    CAS  Google Scholar 

  172. 172.

    Zenhom M, Hyder A, de Vrese M, Heller KJ, Roeder T, Schrezenmeir J (2011) Prebiotic oligosaccharides reduce proinflammatory cytokines in intestinal Caco-2 cells via activation of PPARγ and peptidoglycan recognition protein 3. J Nutr 141:971–977

    CAS  PubMed  Google Scholar 

  173. 173.

    Zeuner B, Vuillemin M, Holck J, Muschiol J, Meyer AS (2018) Loop engineering of an α-1,3/4-l-fucosidase for improved synthesis of human milk oligosaccharides. Enzyme Microb Technol 115:37–44

    CAS  PubMed  Google Scholar 

  174. 174.

    Zhang Z, Ollmann IR, Ye X-S, Wischnat R, Baasov T, Wong C-H (1999) Programmable one-pot oligosaccharide synthesis. J Am Chem Soc 121:734–753

    CAS  Google Scholar 

  175. 175.

    Zivkovic AM, German JB, Lebrilla CB, Mills DA (2011) Human milk glycobiome and its impact on the infant gastrointestinal microbiota. Proc Natl Acad Sci USA 108(Suppl 1):4653–4658

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the Iowa State University Startup Funds. F.E. was supported in part by the Manley Hoppe Professorship and T.J.M. by the Karen and Denny Vaughn Faculty Fellowship.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Thomas J. Mansell.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Enam, F., Mansell, T.J. Prebiotics: tools to manipulate the gut microbiome and metabolome. J Ind Microbiol Biotechnol 46, 1445–1459 (2019). https://doi.org/10.1007/s10295-019-02203-4

Download citation

Keywords

  • Prebiotics
  • Human milk oligosaccharides
  • Gut microbiome