Skip to main content
    • Aa
    • Aa

Prebiotic effects: metabolic and health benefits

  • Marcel Roberfroid (a1), Glenn R. Gibson (a2), Lesley Hoyles (a2), Anne L. McCartney (a2), Robert Rastall (a2), Ian Rowland (a2), Danielle Wolvers (a3), Bernhard Watzl (a4), Hania Szajewska (a5), Bernd Stahl (a6), Francisco Guarner (a7), Frederique Respondek (a8), Kevin Whelan (a9), Veronique Coxam (a10), Marie-Jeanne Davicco (a10), Laurent Léotoing (a10), Yohann Wittrant (a10), Nathalie M. Delzenne (a11), Patrice D. Cani (a11), Audrey M. Neyrinck (a11) and Agnes Meheust (a12)...

The different compartments of the gastrointestinal tract are inhabited by populations of micro-organisms. By far the most important predominant populations are in the colon where a true symbiosis with the host exists that is a key for well-being and health. For such a microbiota, ‘normobiosis’ characterises a composition of the gut ‘ecosystem’ in which micro-organisms with potential health benefits predominate in number over potentially harmful ones, in contrast to ‘dysbiosis’, in which one or a few potentially harmful micro-organisms are dominant, thus creating a disease-prone situation. The present document has been written by a group of both academic and industry experts (in the ILSI Europe Prebiotic Expert Group and Prebiotic Task Force, respectively). It does not aim to propose a new definition of a prebiotic nor to identify which food products are classified as prebiotic but rather to validate and expand the original idea of the prebiotic concept (that can be translated in ‘prebiotic effects’), defined as: ‘The selective stimulation of growth and/or activity(ies) of one or a limited number of microbial genus(era)/species in the gut microbiota that confer(s) health benefits to the host.’ Thanks to the methodological and fundamental research of microbiologists, immense progress has very recently been made in our understanding of the gut microbiota. A large number of human intervention studies have been performed that have demonstrated that dietary consumption of certain food products can result in statistically significant changes in the composition of the gut microbiota in line with the prebiotic concept. Thus the prebiotic effect is now a well-established scientific fact. The more data are accumulating, the more it will be recognised that such changes in the microbiota's composition, especially increase in bifidobacteria, can be regarded as a marker of intestinal health. The review is divided in chapters that cover the major areas of nutrition research where a prebiotic effect has tentatively been investigated for potential health benefits. The prebiotic effect has been shown to associate with modulation of biomarkers and activity(ies) of the immune system. Confirming the studies in adults, it has been demonstrated that, in infant nutrition, the prebiotic effect includes a significant change of gut microbiota composition, especially an increase of faecal concentrations of bifidobacteria. This concomitantly improves stool quality (pH, SCFA, frequency and consistency), reduces the risk of gastroenteritis and infections, improves general well-being and reduces the incidence of allergic symptoms such as atopic eczema. Changes in the gut microbiota composition are classically considered as one of the many factors involved in the pathogenesis of either inflammatory bowel disease or irritable bowel syndrome. The use of particular food products with a prebiotic effect has thus been tested in clinical trials with the objective to improve the clinical activity and well-being of patients with such disorders. Promising beneficial effects have been demonstrated in some preliminary studies, including changes in gut microbiota composition (especially increase in bifidobacteria concentration). Often associated with toxic load and/or miscellaneous risk factors, colon cancer is another pathology for which a possible role of gut microbiota composition has been hypothesised. Numerous experimental studies have reported reduction in incidence of tumours and cancers after feeding specific food products with a prebiotic effect. Some of these studies (including one human trial) have also reported that, in such conditions, gut microbiota composition was modified (especially due to increased concentration of bifidobacteria). Dietary intake of particular food products with a prebiotic effect has been shown, especially in adolescents, but also tentatively in postmenopausal women, to increase Ca absorption as well as bone Ca accretion and bone mineral density. Recent data, both from experimental models and from human studies, support the beneficial effects of particular food products with prebiotic properties on energy homaeostasis, satiety regulation and body weight gain. Together, with data in obese animals and patients, these studies support the hypothesis that gut microbiota composition (especially the number of bifidobacteria) may contribute to modulate metabolic processes associated with syndrome X, especially obesity and diabetes type 2. It is plausible, even though not exclusive, that these effects are linked to the microbiota-induced changes and it is feasible to conclude that their mechanisms fit into the prebiotic effect. However, the role of such changes in these health benefits remains to be definitively proven. As a result of the research activity that followed the publication of the prebiotic concept 15 years ago, it has become clear that products that cause a selective modification in the gut microbiota's composition and/or activity(ies) and thus strengthens normobiosis could either induce beneficial physiological effects in the colon and also in extra-intestinal compartments or contribute towards reducing the risk of dysbiosis and associated intestinal and systemic pathologies.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Prebiotic effects: metabolic and health benefits
      Available formats
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about sending content to Dropbox.

      Prebiotic effects: metabolic and health benefits
      Available formats
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about sending content to Google Drive.

      Prebiotic effects: metabolic and health benefits
      Available formats
The online version of this article is published within an Open Access environment subject to the conditions of the Creative Commons Attribution-NonCommercial-ShareAlike licence . The written permission of Cambridge University Press must be obtained for commercial re-use.
Corresponding author
*Correspondence: ILSI Europe a.i.s.b.l. - Avenue E. Mounier 83, Box 6 - 1200 Brussels - Belgium Email: - Fax: +32 2 762 00 44
Hide All
1Yazawa K, Imai K & Tamura Z (1978) Oligosaccharides and polysaccharides specifically utilizable by bifidobacteria. Chem Pharm Bull (Tokyo) 26, 33063311.
2Mitsuoka T, Hidaka H & Eida T (1987) Effect of fructo-oligosaccharides on intestinal microflora. Nahrung 31, 427436.
3Gibson GR & Roberfroid MB (1995) Dietary modulation of the human colonic microbiota – introducing the concept of prebiotics. J Nutr 125, 14011412.
4Gibson GR, Probert HM, Van Loo J, et al. (2004) Dietary modulation of the human colonic microbiota: updating the concept of prebiotics. Nutr Res Rev 17, 259275.
5Suau A, Bonnet R, Sutren M, et al. (1999) Direct analysis of genes encoding 16S rRNA from complex communities reveals many novel molecular species within the human gut. Appl Environ Microbiol 65, 47994807.
6Harmsen HJ, Elfferich P, Schut P, et al. (1999) A 16S rRNA-targeted probe for detection of lactobacilli and enterococci in fecal samples by fluorescent in situ hybridization. Microb Ecol Health Dis 11, 312.
7Harmsen HJ, Wildeboer-Veloo AC, Grijpstra J, et al. (2000) Development of 16S rRNA-based probes for the Coriobacterium group and the Atopobium cluster and their application for enumeration of Coriobacteriaceae in human feces from volunteers of different age groups. Appl Environ Microbiol 66, 45234527.
8Harmsen HJ, Raangs GC, He T, et al. (2002) Extensive set of 16S rRNA-based probes for detection of bacteria in human feces. Appl Environ Microbiol 68, 29822990.
9Zoetendal EG, Akkermans AD & de Vos WM (1998) Temperature gradient gel electrophoresis analysis of 16S rRNA from human fecal samples reveals stable and host-specific communities of active bacteria. Appl Environ Microbiol 64, 38543859.
10Zoetendal EG, Akkermans AD, Akkermans-van Vliet WM, et al. (2001) The host genotype affects the bacterial community in the human gastrointestinal tract. Microb Ecol Health Dis 13, 129134.
11Zoetendal EG, von Wright A, Vilpponen-Salmela T, et al. (2002) Mucosa-associated bacteria in the human gastrointestinal tract are uniformly distributed along the colon and differ from the community recovered from feces. Appl Environ Microbiol 68, 34013407.
12Wang X, Heazlewood SP, Krause DO, et al. (2003) Molecular characterization of the microbial species that colonize human ileal and colonic mucosa by using 16S rDNA sequence analysis. J Appl Microbiol 95, 508520.
13Wang M, Ahrne S, Jeppsson B, et al. (2005) Comparison of bacterial diversity along the human intestinal tract by direct cloning and sequencing of 16S rRNA genes. FEMS Microbiol Ecol 54, 219231.
14Eckburg PB, Bik EM, Bernstein CN, et al. (2005) Diversity of the human intestinal microbial flora. Science 308, 16351638.
15Hayashi H, Takahashi R, Nishi T, et al. (2005) Molecular analysis of jejunal, ileal, caecal and recto-sigmoidal human colonic microbiota using 16S rRNA gene libraries and terminal restriction fragment length polymorphism. J Med Microbiol 54, 10931101.
16Green GL, Brostoff J, Hudspith B, et al. (2006) Molecular characterization of the bacteria adherent to human colorectal mucosa. J Appl Microbiol 100, 460469.
17Roberfroid M & Gibson GR (2002) Nutritional and health benefits of inulin and oligofructose. Br J Nutr 87, S139S311.
18Roberfroid M & Robertson D (2005) Effects of inulin and oligofructose on health and well-being. Br J Nutr 93, S1S168.
19Roberfroid M & Buddington RK (2007) Inulin and oligofructose: proven health benefits and claims. J Nutr 137, S2489S2597.
20Gibson GR & Roberfroid M (2008) Handbook of Prebiotics. Boca Raton, FL: CRC Press.
21Cummings JH, Antoine JM, Azpiroz F, et al. (2004) PASSCLAIM – gut health and immunity. Eur J Nutr 43, Suppl. 2, II118II173.
22Wilson KH & Blitchington RB (1996) Human colonic biota studied by ribosomal DNA sequence analysis. Appl Environ Microbiol 62, 22732278.
23Kerckhoffs APM, Samson M, van Berge Henegouwen GP, et al. (2006) Sampling microbiota in the human gastrointestinal tract. In Gastrointestinal Microbiology, pp. 2550 [Ouwehand AC and Vaughan EE, editors]. New York: Taylor & Francis Ltd.
24O'Connor EB, Barrett E, Fitzgerald G, et al. (2005) Production of vitamins, exopolysaccharides and bacteriocins by probiotic bacteria. In Probiotic Dairy Products, pp. 167194 [Tamine AY, editor]. Oxford: Blackwell Publishing Ltd.
25O'May GA, Reynolds N, Smith AR, et al. (2005) Effect of pH and antibiotics on microbial overgrowth in the stomachs and duodena of patients undergoing percutaneous endoscopic gastromy feeding. Appl Environ Microbiol 71, 30593065.
26Reuter G (2001) The Lactobacillus and Bifidobacterium microflora of the human intestine: composition and succession. Curr Issues Intest Microbiol 2, 4353.
27O'May GA, Reynolds N & Macfarlane GT (2005) Effect of pH on an in vitro model of gastric microbiota in enteral nutrition patients. Appl Environ Microbiol 71, 47774783.
28Macfarlane GT, Macfarlane S & Gibson GR (1998) Validation of a three-stage compound continuous culture system for investigating the effect of retention time on the ecology and metabolism of bacteria in the human colon. Microb Ecol 35, 180187.
29Duncan SH, Aminov RI, Scott KP, et al. (2006) Proposal of Roseburia faecis sp. nov., Roseburia hominis sp. nov. and Roseburia inulinivorans sp. nov., based on isolates from human faeces. Int J Syst Evol Microbiol 56, 24372441.
30Derrien M, Vaughan EE, Plugge CM, et al. (2004) Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium. Int J Syst Evol Microbiol 54, 14691476.
31Walker AW, Duncan SH, William Leitch EC, et al. (2005) pH and peptide supply can radically alter bacterial populations and short-chain fatty acid ratios within microbial communities from the human colon. Appl Environ Microbiol 71, 36923700.
32Blaut M, Collins MD, Welling GW, et al. (2002) Molecular biological methods for studying the gut microbiota: the EU human gut flora project. Br J Nutr 87, Suppl. 2, S203S211.
33Manichanh C, Rigottier-Gois L, Bonnaud E, et al. (2006) Reduced diversity of faecal microbiota in Crohn's disease revealed by a metagenomic approach. Gut 55, 205211.
34Stewart JA, Chadwick VS & Murray A (2005) Investigations into the influence of host genetics on the predominant eubacteria in the faecal microflora of children. J Med Microbiol 54, 12391242.
35Cherbut C (2003) Motor effects of short-chain fatty acids and lactate in the gastrointestinal tract. Proc Nutr Soc 62, 9599.
36Flint HJ, Bayer EA, Rincon MT, et al. (2008) Polysaccharide utilization by gut bacteria: potential for new insights from genomic analysis. Nat Rev Microbiol 6, 121131.
37Cummings JH & Macfarlane GT (1991) The control and consequences of bacterial fermentation in the human colon. J Appl Bacteriol 70, 443459.
38Rowland IR, Mallett AK & Wise A (1985) The effect of diet on the mammalian gut flora and its metabolic activities. Crit Rev Toxicol 16, 31103.
39Topping DL & Clifton PM (2001) Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides. Physiol Rev 81, 10311064.
40Lupton J (2004) Microbial degradation products influence colon cancer risk: the butyrate controversy. J Nutr 134, 479482.
41Macfarlane GT, Gibson GR & Cummings JH (1992) Comparison of fermentation reactions in different regions of the human colon. J Appl Bacteriol 72, 5764.
42Bingham SA, Pett S & Day KC (1990) NSP intake of a representative sample of British adults. J Hum Nutr Diet 3, 339344.
43Gray J (2006) Dietary Fibre: Definition, Analysis, Physiology and Health. Brussels: International Life Sciences Institute.
44Englyst HN & Macfarlane GT (1986) Breakdown of resistant and readily digestible starch by human gut bacteria. J Sci Food Agric 37, 699706.
45Hudson M & Marsh PD (1995) Carbohydrate metabolism in the colon. In Human Colonic Bacteria: Role in Nutrition, Physiology and Pathology, pp. 6172 [Gibson GR and Macfarlane GT, editors]. Boca Raton, FL: CRC Press.
46Scientific Opinion of the Panel on Dietetic Products, Nutrition and Allergies on a request from the EC on population reference intakes for carbohydrates and dietary fibre. (2009).
47Quigley ME & Kelly S (1995) Structure, function, and metabolism of host mucus glycoproteins. In Human Colonic Bacteria: Role in Nutrition, Physiology and Pathology, pp. 175199 [Gibson GR and Macfarlane GT, editors]. Boca Raton, FL: CRC Press.
48Macfarlane S & Macfarlane GT (1995) Proteolysis and amino acid fermentation. In Human Colonic Bacteria: Role in Nutrition, Physiology and Pathology, pp. 75100 [Gibson GR and Macfarlane GT, editors]. Boca Raton, FL: CRC Press.
49Cummings JH (1981) Short chain fatty acids in the human colon. Gut 22, 763779.
50Cummings JH (1995) Short chain fatty acids. In Human Colonic Bacteria: Role in Nutrition, Physiology and Pathology, pp. 101130 [Gibson GR and Macfarlane GT, editors]. Boca Raton, FL: CRC Press.
51Flint HJ (2006) Prokaryote diversity in the human GI tract. In Prokaryotic Diversity: Mechanisms and Significance, Society for General Microbiology Symposium no. 66, Warwick April 2006, pp. 6590 [Logan N, Lappin-Scott H and Oyston P, editors]. Cambridge, MA: Cambridge University Press.
52Levitt MD, Gibson GR & Christl S (1995) Gas metabolism in the large intestine. In Human Colonic Bacteria: Role in Nutrition, Physiology and Health, pp. 113154 [Gibson GR and Macfarlane GT, editors]. Boca Raton, FL: CRC Press.
53Blaut M (2002) Relationship of prebiotics and food to intestinal microflora. Eur J Nutr 1, Suppl. 1, I11I16.
54Dass NB, John AK, Bassil AK, et al. (2007) The relationship between the effects of short-chain fatty acids on intestinal motility in vitro and GPR43 receptor activation. Neurogastroenterol Motil 19, 6674.
55Engelhardt W, Busche R, Gros G, et al. (1991) Absorption of short-chain fatty acids: mechanisms and regional differences in the large intestine. In Short-Chain Fatty Acids: Metabolism and Clinical Importance, pp. 6062 [Cummings JH, Rombeau J and Sakata T, editors]. Columbus, OH: Ross Laboratories Press.
56Vogt JA & Wolever TM (2003) Fecal acetate is inversely related to acetate absorption from the human rectum and distal colon. J Nutr 133, 31453148.
57Reshef L, Niv J & Shapiro B (1967) Effect of propionate on lipogenesis in adipose tissue. J Lipid Res 8, 682687.
58Siong Y, Miyamoto N, Shibata K, et al. (2004) Short-chain fatty acids stimulate leptin production in adipocytes through the G protein-coupled receptor GPR41. PNAS 4, 10451050.
59Williams EA, Coxhead JM & Mathers JC (2003) Anti-cancer effects of butyrate: use of micro-array technology to investigate mechanisms. Proc Nutr Soc 62, 107115.
60Scheppach W (1996) Treatment of distal ulcerative colitis with short-chain fatty acid enemas. A placebo-controlled trial. German-Austrian SCFA Study Group. Dig Dis Sci 41, 22542259.
61Tamura Z (1983) Nutriology of bifidobacteria. Bifidobact Microfl 2, 316.
62Hughes SA, Shewry PR, Li L, et al. (2007) In vitro fermentation by human fecal microflora of wheat arabinoxylans. J Agric Food Chem 55, 45894595.
63Wang X & Gibson GR (1993) Effects of the in vitro fermentation of oligofructose and inulin by bacteria growing in the human large intestine. J Appl Bacteriol 75, 373380.
64Rycroft CE, Jones MR, Gibson GR, et al. (2001) A comparative in vitro evaluation of the fermentation properties of prebiotic oligosaccharides. J Appl Microbiol 91, 878887.
65Hayakawa K, Mizutani J, Wada K, et al. (1990) Effects of soybean oligosaccharides on human faecal flora. Microbial Ecol Health Dis 3, 293303.
66Sghir A, Chow JM & Mackie RI (1998) Continuous culture selection of bifidobacteria and lactobacilli from human faecal samples using fructooligosaccharide as selective substrate. J Appl Microbiol 85, 769777.
67Gibson GR & Wang X (1994) Enrichment of bifidobacteria from human gut contents by oligofructose using continuous culture. FEMS Microbiol Lett 118, 121127.
68Gibson GR & Wang X (1994) Regulatory effects of bifidobacteria on the growth of other colonic bacteria. J Appl Bacteriol 77, 412420.
69McBain AJ & Macfarlane GT (1997) Investigations of bifidobacterial ecology and oligosaccharide metabolism in a three-stage compound continuous culture system. Scand J Gastroenterol Suppl 222, 3240.
70McBain AJ & Macfarlane GT (2001) Modulation of genotoxic enzyme activities by non-digestible oligosaccharide metabolism in in-vitro human gut bacterial ecosystems. J Med Microbiol 50, 833842.
71Wada K, Watabe J, Mizutani J, et al. (1992) Effects of soybean oligosaccharides in a beverage on human fecal flora and metabolites. J Agric Chem Soc Japan 66, 127135.
72Palframan RJ, Gibson GR & Rastall RA (2002) Effect of pH and dose on the growth of gut bacteria on prebiotic carbohydrates in vitro. Anaerobe 8, 287292.
73Tzortzis G, Goulas AK, Gee JM, et al. (2005) A novel galactooligosaccharide mixture increases the bifidobacterial population numbers in a continuous in vitro fermentation system and in the proximal colonic contents of pigs. In Vivo J Nutr 135, 17261731.
74van de Wiele T, Boon N, Possemiers S, et al. (2004) Prebiotic effects of chicory inulin in the simulator of the human intestinal microbial ecosystem. FEMS Microbiol Ecol 51, 143153.
75van de Wiele T, Boon N, Possemiers S, et al. (2007) Inulin-type fructans of longer degree of polymerization exert more pronounced in vitro prebiotic effects. J Appl Microbiol 102, 452460.
76Minekus M, Smeets-Peeters M, Bernalier A, et al. (1999) A computer-controlled system to simulate conditions of the large intestine with peristaltic mixing, water absorption and absorption of fermentation products. Appl Microbiol Biotechnol 53, 108114.
77Venema K, van Nuenen MHMC, van den Heuvel EG, et al. (2003) The effect of lactulose on the composition of the intestinal microbiota and short-chain fatty acid production in human volunteers and a computercontrolled model of the proximal large intestine. Microb Ecol Health Dis 15, 94105.
78Roberfroid M (2005) Inulin-Type Fructans. Functional Food Ingredients. Boca Raton, FL: CRC Press.
79Murphy K, Travers P & Walport M (2007) Janeway's Immunobiology, 7th ed.New York: Garland Publishing.
80Albers R, Antoine JM, Bourdet-Sicard R, et al. (2005) Markers to measure immunomodulation in human nutrition intervention studies. Br J Nutr 94, 452481.
81Wagner RD (2008) Effects of microbiota on GI health: gnotobiotic research. Gi Microb Regul Immune Sys 635, 4156.
82Kelly D, King T & Aminov R (2007) Importance of microbial colonization of the gut in early life to the development of immunity. Mutat Res 622, 5869.
83Round JL & Mazmanian SK (2009) The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol 9, 313323.
84Gaboriau-Routhiau V, Rakotobe S, Lecuyer E, et al. (2009) The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity 31, 677689.
85Rescigno M, Urbano M, Valzasina B, et al. (2001) Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat Immunol 2, 361367.
86Sanderson IR (2007) Dietary modulation of GALT. J Nutr 137, 2557S2562S.
87Artis D (2008) Epithelial-cell recognition of commensal bacteria and maintenance of immune homeostasis in the gut. Nat Rev Immunol 8, 411420.
88Medzhitov R (2007) Recognition of microorganisms and activation of the immune response. Nature 449, 819826.
89Vance RE, Isberg RR & Portnoy DA (2009) Patterns of pathogenesis: discrimination of pathogenic and nonpathogenic microbes by the innate immune system. Cell Host Microbe 6, 1021.
90Rakoff-Nahoum S, Paglino J, Eslami-Varzaneh F, et al. (2004) Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell 118, 229241.
91Nilsson NE, Kotarsky K, Owman C, et al. (2003) Identification of a free fatty acid receptor, FFA2R, expressed on leukocytes and activated by short-chain fatty acids. Biochem Biophys Res Commun 303, 10471052.
92Le Poul E, Loison C, Struyf S, et al. (2003) Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation. J Biol Chem 278, 2548125489.
93Karaki S, Tazoe H, Hayashi H, et al. (2008) Expression of the short-chain fatty acid receptor, GPR43, in the human colon. J Mol Histol 39, 135142.
94Tazoe H, Otomo Y, Karaki S, et al. (2009) Expression of short-chain fatty acid receptor GPR41 in the human colon. Biomed Res 30, 149156.
95Cavaglieri CR, Nishiyama A, Fernandes LC, et al. (2003) Differential effects of short-chain fatty acids on proliferation and production of pro- and anti-inflammatory cytokines by cultured lymphocytes. Life Sci 73, 16831690.
96Maslowski KM, Vieira AT, Ng A, et al. (2009) Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature 461, 12821286.
97Schley PD & Field CJ (2002) The immune-enhancing effects of dietary fibres and prebiotics. Br J Nutr 87, Suppl. 2, S221S230.
98Watzl B, Girrbach S & Roller M (2005) Inulin, oligofructose and immunomodulation. Br J Nutr 93, S49S55.
99Seifert S & Watzl B (2007) Inulin and oligofructose: review of experimental data on immune modulation. J Nutr 137, 2563S2567S.
100Lomax AR & Calder PC (2009) Prebiotics, immune function, infection and inflammation: a review of the evidence. Br J Nutr 101, 633658.
101Seifert S & Watzl B (2008) Prebiotics and the immune system: review of experimental and human data. In Handbook of Prebiotics, pp. 143162 [Gibson GR and Roberfroid M, editors]. Boca Raton, FL: CRC Press.
102Bunout D, Hirsch S, Pia DLM, et al. (2002) Effects of prebiotics on the immune response to vaccination in the elderly. JPEN J Parenter Enteral Nutr 26, 372376.
103Bunout D, Barrera G, Hirsch S, et al. (2004) Effects of a nutritional supplement on the immune response and cytokine production in free-living Chilean elderly. JPEN J Parenter Enteral Nutr 28, 348354.
104Duggan C, Penny ME, Hibberd P, et al. (2003) Oligofructose-supplemented infant cereal: 2 randomized, blinded, community-based trials in Peruvian infants. Am J Clin Nutr 77, 937942.
105van Hoffen E, Ruiter B, Faber J, et al. (2009) A specific mixture of short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides induces a beneficial immunoglobulin profile in infants at high risk for allergy. Allergy 64, 484487.
106Bakker-Zierikzee AM, Tol EA, Kroes H, et al. (2006) Faecal SIgA secretion in infants fed on pre- or probiotic infant formula. Pediatr Allergy Immunol 17, 134140.
107Scholtens PA, Alliet P, Raes M, 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, 11411147.
108Guigoz Y, Rochat F, Perruisseau-Carrier G, et al. (2002) Effects of oligosaccharide on the faecal flora and non-specific immune system in elderly people. Nutr Res 22, 1325.
109Shadid R, Haarman M, Knol J, et al. (2007) Effects of galactooligosaccharide and long-chain fructooligosaccharide supplementation during pregnancy on maternal and neonatal microbiota and immunity – a randomized, double-blind, placebo-controlled study. Am J Clin Nutr 86, 14261437.
110Vulevic J, Drakoularakou A, Yaqoob P, et al. (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, 14381446.
111Lindsay J, Whelan K, Stagg A, et al. (2006) Clinical, microbiological, and immunological effects of fructo-oligosaccharide in patients with Crohn's disease. Gut 55, 348355.
112Hoentjen F, Welling GW, Harmsen HJ, et al. (2005) Reduction of colitis by prebiotics in HLA-B27 transgenic rats is associated with microflora changes and immunomodulation. Inflamm Bowel Dis 11, 977985.
113Moro G, Arslanoglu S, Stahl B, et al. (2006) A mixture of prebiotic oligosaccharides reduces the incidence of atopic dermatitis during the first six months of age. Arch Dis Child 91, 814819.
114Fukasawa T, Murashima K, Matsumoto I, et al. (2007) Identification of marker genes for intestinal immunomodulating effect of a fructooligosaccharide by DNA microarray analysis. J Agric Food Chem 55, 31743179.
115Roller M, Pietro FA, Caderni G, et al. (2004) Intestinal immunity of rats with colon cancer is modulated by oligofructose-enriched inulin combined with Lactobacillus rhamnosus and Bifidobacterium lactis. Br J Nutr 92, 931938.
116Roller 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, 153156.
117Girrbach S, Schroeder B, Breves G, et al. (2005) Short- and long-term supplementation of pre- and probiotics modulate T-cell mediated immunity of the porcine GALT. FASEB J 19, A444A445.
118Agostoni C, Axelsson I, Goulet O, et al. (2004) Prebiotic oligosaccharides in dietetic products for infants: a commentary by the ESPGHAN Committee on Nutrition. J Pediatr Gastroenterol Nutr 39, 465473.
119Boehm G & Moro G (2008) Structural and functional aspects of prebiotics used in infant nutrition. J Nutr 138, 1818S1828S.
120Yap WKW, Mohamed S, Husni JM, et al. (2008) Changes in infants faecal characteristics and microbiota by inulin supplementation. J Clin Nutr Biochem 43, 159166.
121Ben XM, Zhou XY, Zhao WH, et al. (2004) Supplementation of milk formula with galacto-oligosaccharides improves intestinal micro-flora and fermentation in term infants. Chin Med J (Engl) 117, 927931.
122Ben XM, Li J, Feng ZT, et al. (2008) Low level of galacto-oligosaccharide in infant formula stimulates growth of intestinal Bifidobacteria and Lactobacilli. World J Gastroenterol 14, 65646568.
123Fanaro S, Marten B, Bagna R, et al. (2009) Galacto-oligosaccharides are bifidogenic and safe at weaning: a double-blind randomized multicenter study. J Pediatr Gastroenterol Nutr 48, 8288.
124Magne F, Hachelaf W, Suau A, et al. (2008) Effects on faecal microbiota of dietary and acidic oligosaccharides in children during partial formula feeding. J Pediatr Gastroenterol Nutr 46, 580588.
125Commission Directive 2006/141/EC on infant formulae and follow-on formulae and amending Directive 1999/21/EC. (2006) Official J Eur Union L401, 133.
126Moore N, Chao C, Yang LP, et al. (2003) Effects of fructo-oligosaccharide-supplemented infant cereal: a double-blind, randomized trial. Br J Nutr 90, 581587.
127Scholtens PA, Alles MS, Bindels JG, et al. (2006) Bifidogenic effects of solid weaning foods with added prebiotic oligosaccharides: a randomised controlled clinical trial. J Pediatr Gastroenterol Nutr 42, 553559.
128Lien do TK, Nhung BT, Khan NC, et al. (2009) Impact of milk consumption on performance and health of primary school children in rural Vietnam. Asia Pac J Clin Nutr 18, 326334.
129Bruzzese E, Volpicelli M, Squeglia V, et al. (2009) A formula containing galacto- and fructo-oligosaccharides prevents intestinal and extra-intestinal infections: an observational study. Clin Nutr 28, 156161.
130Arslanoglu 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, 24202424.
131Hoekstra JH, Szajewska H, Zikri MA, et al. (2004) Oral rehydration solution containing a mixture of non-digestible carbohydrates in the treatment of acute diarrhea: a multicenter randomized placebo controlled study on behalf of the ESPGHAN working group on intestinal infections. J Pediatr Gastroenterol Nutr 39, 239245.
132Surawicz CM (2003) Probiotics, antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in humans. Best Pract Res Clin Gastroenterol 17, 775783.
133D'Souza AL, Rajkumar C, Cooke J, et al. (2002) Probiotics in prevention of antibiotic associated diarrhoea: meta-analysis. BMJ 324, 1361.
134Cremonini F, Di CS, Nista EC, et al. (2002) Meta-analysis: the effect of probiotic administration on antibiotic-associated diarrhoea. Aliment Pharmacol Ther 16, 14611467.
135Szajewska H & Mrukowicz J (2005) Meta-analysis: non-pathogenic yeast Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea. Aliment Pharmacol Ther 22, 365372.
136Hawrelak JA, Whitten DL & Myers SP (2005) Is Lactobacillus rhamnosus GG effective in preventing the onset of antibiotic-associated diarrhoea: a systematic review. Digestion 72, 5156.
137Szajewska H, Ruszczynski M & Radzikowski A (2006) Probiotics in the prevention of antibiotic-associated diarrhea in children: a meta-analysis of randomized controlled trials. J Pediatr 149, 367372.
138Brunser O, Gotteland M, Cruchet S, et al. (2006) Effect of a milk formula with prebiotics on the intestinal microbiota of infants after an antibiotic treatment. Pediatr Res 59, 451456.
139Kalliomaki M, Kirjavainen P, Eerola E, et al. (2001) Distinct patterns of neonatal gut microflora in infants in whom atopy was and was not developing. J Allergy Clin Immunol 107, 129134.
140Osborn DA & Sinn JK (2007) Prebiotics in infants for prevention of allergic disease and food hypersensitivity. The Cochrane Database of Systematic Reviews 2007, CD006474.
141Arslanoglu S, Moro GE, Schmitt J, et al. (2008) 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 138, 10911095.
142Cummings JH, Christie S & Cole TJ (2001) A study of fructo oligosaccharides in the prevention of travellers' diarrhoea. Aliment Pharmacol Ther 15, 11391145.
143Lewis S, Burmeister S, Cohen S, et al. (2005) Failure of dietary oligofructose to prevent antibiotic-associated diarrhoea. Aliment Pharmacol Ther 21, 469477.
144Lewis 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, 442448.
145Spiller R, Aziz Q, Creed F, et al. (2007) Guidelines on the irritable bowel syndrome: mechanism and practical management. Gut 56, 17701798.
146Longstreth GF, Thompson WG, Chey WD, et al. (2006) Functional bowel disorders. Gastroenterology 130, 14801491.
147Serra J, Salvioli B, Azpiroz F, et al. (2002) Lipid-induced intestinal gas retention in irritable bowel syndrome. Gastroenterology 123, 700706.
148Spiller R (2008) Review Article: probiotics and prebiotics in irritable bowel syndrome. Aliment Pharmacol Ther 28, 385396.
149Balsari A, Ceccarelli A, Dubini F, et al. (1982) The fecal microbial population in the irritable bowel syndrome. Microbiologica 5, 185194.
150Si JM, Yu YC, Fan YF, et al. (2004) Intestinal microecology and quality of life in irritable bowel syndrome patients. World J Gastroenterol 10, 18021805.
151Malinen EM, Rinttilä T, Kajander K, et al. (2005) Analysis of the fecal microbiota of irritable bowel syndrome patients and healthy controls with real-time PCR. Am J Gastroenterol 100, 373382.
152Chassard D, Marquet P, Del'Homme C, et al. (2006) Distribution of the main functionnal groups of micro-organims in the gut of IBS patients. Reprod Nutr Develop Suppl. 1, S4, (Abstract).
153Kassinen A, Krogius L, Mäkivuokko H, et al. (2007) The fecal microbiota of irritable bowel syndrome patients differs significantly from that of healthy subjects. Gastroenterology 133, 2433.
154Kerckhoffs APM, Samsom M, van der Rest ME, et al. (2009) Lower bifidobacteria counts in both duodenal mucose-associated and faecal microbiota in irritable bowel syndrome patients. World J Gastroenterol 15, 28872892.
155Maukonen J, Satokari R, Mattö J, et al. (2006) Prevalence and temporal stability of selected clostridal groups in irritable bowel syndrome in relation to predominant faecal bacteria. J Med Microbiol 55, 625633.
156Nyman M (2002) Fermentation and bulking capacity of indigestible carbohydrates: the case of inulin and oligofructose. Br J Nutr 87, S163S168.
157de Preter V, Vanhoutte T, Huys G, et al. (2008) Baseline microbiota activity and initial bifidobacteria counts influence responses to prebiotic dosing in healthy subjects. Aliment Pharmacol Ther 27, 504513.
158Furrie E, Macfarlane S, Kennedy A, et al. (2005) Synbiotic therapy (Bifidobacterium longum/Synergy 1) initiates resolution of inflammation in patients with active ulcerative colitis: a randomised controlled pilot trial. Gut 54, 1346.
159Casellas F, Borruel N, Torrejon A, et al. (2007) Oral oligofructose-enriched inulin supplementation in acute ulcerative colitis is well tolerated and associated with lowered faecal calprotectin. Aliment Pharmacol Ther 25, 10611067.
160Cook KF, Rabeneck L, Campbell CJ, et al. (1999) Evaluation of a multidimensional measure of dyspepsia-related health for use in a randomized clinical trial. J Clin Epidemiol 52, 381392.
161Olesen M & Gudmand-Hoyer E (2000) Efficacy, safety, and tolerability of fructooligosaccharides in the treatment of irritable bowel syndrome. Am J Clin Nutr 72, 15701575.
162Hunter JO, Tuffnell Q & Lee AJ (1999) Controled trial of oligofructose in the management of irritable bowel syndrome. J Nutr 129, 1451S1453S.
163Irvine EJ, Whitehead WE, Chey WD, et al. (2006) Design of treatment trials for functional gastrointestinal disorders. Gastroenterology 133, 2433.
164Dughera L, Elia C, Navino M, et al. (2007) Effects of synbiotic preparations on constipated irritable bowel syndrome symptoms. Acta Biomed 78, 111116.
165Paineau D, Payen F, Panserieu S, et al. (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, 311318.
166Silk DBA, Davis A, Vulevic J, et al. (2009) Clinical trial: the effects of a trans-galactooligosaccharide prebiotic on faecal microbiota and symptoms in irritable bowel syndrome. Aliment Pharmacol Ther 29, 508518.
167Loftus EV Jr (2004) Clinical epidemiology of inflammatory bowel disease: incidence, prevalence, and environmental influences. Gastroenterology 126, 15041517.
168Travis SP, Stange EF, Lemann M, et al. (2006) European Crohn's and Colitis Organisation. European evidence based consensus on the diagnosis and management of Crohn's disease: current management. Gut 55, 1635.
169Lucendo AJ & De Rezende LC (2009) Importance of nutrition in inflammatory bowel disease. World J Gastroenterol 15, 20812088.
170Irvine EJ (1997) Quality of life issues in patients with inflammatory bowel disease. Am J Gastroenterol 92, 18S24S.
171Schwartz M & Cohen R (2008) Optimizing conventional therapy for inflammatory bowel disease. Curr Gastroenterol Rep 10, 585590.
172Carter MJ, Lobo AJ & Travis SP (2004) Guidelines for the management of inflammatory bowel disease in adults. Gut 53, Suppl. 5, V1V16.
173Zachos M, Tondeur M & Griffiths AM (2007) Enteral nutritional therapy for induction of remission in Crohn's disease. The Cochrane Database of Systematic Reviews 2007, CD000542.
174Teahon K, Pearson M, Levi AJ, et al. (1995) Practical aspects of enteral nutrition in the management of Crohn's disease. J Parenter Enteral Nutr 19, 365368.
175Neuman MG (2007) Immune dysfunction in inflammatory bowel disease. Transl Res 149, 173186.
176Lindsay JO & Hodgson HJ (2001) The immunoregulatory cytokine interleukin-10 – a therapy for Crohn's disease? Aliment Pharmacol Ther 15, 16.
177Brown SJ & Mayer L (2007) The immune response in inflammatory bowel disease. Am J Gastroenterol 102, 20582069.
178Sellon RK, Tonkonogy S, Schultz M, et al. (1998) Resident enteric bacteria are necessary for development of spontaneous colitis and immune system activation in interleukin-10-deficient mice. Infect Immun 66, 52245231.
179Fasoli R, Kettlewell MG, Mortensen N, et al. (1990) Response to faecal challenge in defunctioned colonic Crohn's disease: prediction of long-term course. Br J Surg 77, 616617.
180Chichlowski M & Hale LP (2008) Bacterial-mucosal interactions in inflammatory bowel disease: an alliance gone bad. Am J Physiol Gastrointest Liver Physiol 295, G1139G1149.
181Hugot JP, Chamaillard M, Zouali H, et al. (2001) Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature 411, 599603.
182Zhang H, Massey D, Tremelling M, et al. (2008) Genetics of inflammatory bowel disease: clues to pathogenesis. Br Med Bull 87, 1730.
183Miyauchi E, Morita H & Tanabe S (2009) Lactobacillus rhamnosus alleviates intestinal barrier dysfunction in part by increasing expression of zonula occludens-1 and myosin light-chain kinase in vivo. J Dairy Sci 92, 24002408.
184Garcia VE, De Lourdes De Abreu Ferrari M, Oswaldo Da Gama TH, et al. (2008) Influence of Saccharomyces boulardii on the intestinal permeability of patients with Crohn's disease in remission. Scand J Gastroenterol 43, 842848.
185Hart AL, Lammers K, Brigidi P, et al. (2004) Modulation of human dendritic cell phenotype and function by probiotic bacteria. Gut 53, 16021609.
186Ng SC, Plamondon S, Hart AL, et al. (2008) Effective probiotic treatment (VSL# 3), but not placebo, in acute ulcerative colitis is associated with down-regulation of inflammatory intestinal dendritic cells. Gut 57, A37.
187Sartor RB (2008) Microbial influences in inflammatory bowel diseases. Gastroenterology 134, 577594.
188Hedin C, Whelan K & Lindsay JO (2007) Evidence for the use of probiotics and prebiotics in inflammatory bowel disease: a review of clinical trials. Proc Nutr Soc 66, 307315.
189Seksik P, Rigottier-Gois L, Gramet G, et al. (2003) Alterations of the dominant faecal bacterial groups in patients with Crohn's disease of the colon. Gut 52, 237242.
190Sokol H, Seksik P, Furet JP, et al. (2009) Low counts of Faecalibacterium prausnitzii in colitis microbiota. Inflamm Bowel Dis 15, 11831189.
191Macfarlane S, Furrie E, Cummings JH, et al. (2004) Chemotaxonomic analysis of bacterial populations colonizing the rectal mucosa in patients with ulcerative colitis. Clin Infect Dis 38, 16901699.
192Mylonaki M, Rayment NB, Rampton DS, et al. (2005) Molecular characterization of rectal mucosa-associated bacterial flora in inflammatory bowel disease. Inflamm Bowel Dis 11, 481487.
193Swidsinski A, Ladhoff A, Pernthaler A, et al. (2002) Mucosal flora in inflammatory bowel disease. Gastroenterology 122, 4454.
194Frank DN, St Amand AL, Feldman RA, et al. (2007) Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci U S A 104, 1378013785.
195Sokol H, Lepage P, Seksik P, et al. (2006) Temperature gradient gel electrophoresis of fecal 16S rRNA reveals active Escherichia coli in the microbiota of patients with ulcerative colitis. J Clin Microbiol 44, 31723177.
196Martinez-Medina M, Aldeguer X, Gonzalez-Huix F, et al. (2006) Abnormal microbiota composition in the ileocolonic mucosa of Crohn's disease patients as revealed by polymerase chain reaction-denaturing gradient gel electrophoresis. Inflamm Bowel Dis 12, 11361145.
197Sokol H, Pigneur B, Watterlot L, et al. (2008) Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci U S A 105, 1673116736.
198Kolida S & Gibson GR (2007) Prebiotic capacity of inulin-type fructans. J Nutr 137, 2503S2506S.
199Langlands SJ, Hopkins MJ, Coleman N, et al. (2004) Prebiotic carbohydrates modify the mucosa associated microflora of the human large bowel. Gut 53, 16101616.
200Ramirez-Farias C, Slezak K, Fuller Z, et al. (2009) Effect of inulin on the human gut microbiota: stimulation of Bifidobacterium adolescentis and Faecalibacterium prausnitzii. Br J Nutr 101, 541550.
201Burger-van PN, Vincent A, Puiman PJ, et al. (2009) The regulation of intestinal mucin MUC2 expression by short-chain fatty acids: implications for epithelial protection. Biochem J 420, 211219.
202Pullan RD, Thomas GA, Rhodes M, et al. (1994) Thickness of adherent mucus gel on colonic mucosa in humans and its relevance to colitis. Gut 35, 353359.
203Leenen CH & Dieleman LA (2007) Inulin and oligofructose in chronic inflammatory bowel disease. J Nutr 137, 2572S2575S.
204Hedin CRH, Graczer M, Sanderson JD, et al. (2009) Probiotic and prebiotic use by patients with inflammatory bowel disease. Proc Nutr Soc 68, E36.
205Friedman G & George J (2000) Treatment of refractory ‘pouchitis’ with prebiotic and probiotic therapy. Gastroenterology 118, A778.
206Welters CF, Heineman E, Thunnissen FB, et al. (2002) Effect of dietary inulin supplementation on inflammation of pouch mucosa in patients with an ileal pouch-anal anastomosis. Dis Colon Rectum 45, 621627.
207Kanauchi O, Mitsuyama K, Homma T, et al. (2003) Treatment of ulcerative colitis patients by long-term administration of germinated barley foodstuff: multi-center open trial. Int J Mol Med 12, 701704.
208Hanai H, Kanauchi O, Mitsuyama K, et al. (2004) Germinated barley foodstuff prolongs remission in patients with ulcerative colitis. Int J Mol Med 13, 643647.
209Fujimori S, Gudis K, Mitsui K, et al. (2009) A randomized controlled trial on the efficacy of synbiotic versus probiotic or prebiotic treatment to improve the quality of life in patients with ulcerative colitis. Nutrition 25, 520525.
210Hussey TA, Issenman RM, Persad R, et al. (2003) Nutrition therapy in pediatric Crohn's disease patients improves nutritional status and decreases inflammation. J Pediatr Gastroenterol Nutr 37, .
211Benjamin JL, Hedin CRH, Koutsoumpas A, et al. (2010) No clinical benefit of prebiotics in the treatment of active Crohn's disease: a double-blind, randomised, placebo-controlled trial. Gut, 59: S1-OC-003-A1.
212Chermesh I, Tamir A, Reshef R, et al. (2007) Failure of Synbiotic 2000 to prevent postoperative recurrence of Crohn's disease. Dig Dis Sci 52, 385389.
213Su C, Lewis JD, Goldberg B, et al. (2007) A meta-analysis of the placebo rates of remission and response in clinical trials of active ulcerative colitis. Gastroenterology 132, 516526.
214Su C, Lichtenstein GR, Krok K, et al. (2004) A meta-analysis of the placebo rates of remission and response in clinical trials of active Crohn's disease. Gastroenterology 126, 12571269.
215World Cancer Research Fund/American Institute for cancer research (2007) Food, Nutrition, Physical Activity, and the Prevention of Cancer: A Global Perspective. Washington, DC: WCRF/AICR.
216Rowland I (2009) The role of the gastrointestinal microflora in colorectal cancer. Curr Pharmaceut Design 15, 15241527.
217Hughes R & Rowland I (2003) Nutritional and microbial modification of carcinogenesis. In Gut Flora, Nutrition, Immunity and Health, pp. 208236 [Fuller R and Perdigon G, editors]. Oxford: Blackwell Publishing.
218Rowland IR (1995) Toxicology of the colon – role of the intestinal microflora. In Human Colonic Bacteria, Role in Nutrition, Physiology and Pathology, pp. 155174 [Macfarlane GT and Gibson GR, editors]. Boca Raton, FL: CRC Press.
219Saito Y, Takano T & Rowland I (1992) Effects of soybean oligosaccharides on the human gut microflora in in vitro culture. Microb Ecol Health Dis 5, 105110.
220Reddy BS & Rivenson A (1993) Inhibitory effect of Bifidobacterium longum on colon, mammary, and liver carcinogenesis induced by 2-amino-3-methylimidazo[4,5-f]quinoline, a food mutagen. Cancer Res 53, 39143918.
221Rowland IR, Rumney CJ, Coutts JT, et al. (1998) Effect of Bifidobacterium longum and inulin on gut bacterial metabolism and carcinogen-induced aberrant crypt foci in rats. Carcinogenesis 19, 281285.
222Hidaka H, Eida T, Takizawa T, et al. (1986) Effects of fructooligosaccharides on intestinal flora and human health. Bifidobact Microfl 5, 3750.
223Rowland IR & Tanaka R (1993) The effects of transgalactosylated oligosaccharides on gut flora metabolism in rats associated with a human faecal microflora. J Appl Bacteriol 74, 667674.
224Tanaka R, Takayama H, Morotomi M, et al. (1983) Effects of administration of TOS and Bifidobacterium breve 4006 on the human fecal flora. Bifidobact Microfl 2, 1724.
225Gostner A, Blaut M, Schaffer V, et al. (2006) Effect of isomalt consumption on faecal microflora and colonic metabolism in healthy volunteers. Br J Nutr 95, 4050.
226Pretlow TP, O'Riordan MA, Somich GA, et al. (1992) Aberrant crypts correlate with tumor incidence in F344 rats treated with azoxymethane and phytate. Carcinogenesis 13, 15091512.
227Rao CV, Chou D, Simi B, et al. (1998) Prevention of colonic aberrant crypt foci and modulation of large bowel microbial activity by dietary coffee fiber, inulin and pectin. Carcinogenesis 19, 18151819.
228Gallaher DD, Stallings WH, Blessing LL, et al. (1996) Probiotics, cecal microflora, and aberrant crypts in the rat colon. J Nutr 126, 13621371.
229Verghese M, Rao DR, Chawan CB, et al. (2002) Dietary inulin suppresses azoxymethane-induced preneoplastic aberrant crypt foci in mature Fisher 344 rats. J Nutr 132, 28042808.
230Reddy BS, Hamid R & Rao CV (1997) Effect of dietary oligofructose and inulin on colonic preneoplastic aberrant crypt foci inhibition. Carcinogenesis 18, 13711374.
231Buddington KK, Donahoo JB & Buddington RK (2002) Dietary oligofructose and inulin protect mice from enteric and systemic pathogens and tumor inducers. J Nutr 132, 472477.
232Poulsen M, Molck AM & Jacobsen BL (2002) Different effects of short- and long-chained fructans on large intestinal physiology and carcinogen-induced aberrant crypt foci in rats. Nutr Cancer 42, 194205.
233Jacobsen H, Poulsen M, Dragsted LO, et al. (2006) Carbohydrate digestibility predicts colon carcinogenesis in azoxymethane-treated rats. Nutr Cancer 55, 163170.
234Caderni G, Femia AP, Giannini A, et al. (2003) Identification of mucin-depleted foci in the unsectioned colon of azoxymethane-treated rats: correlation with carcinogenesis. Cancer Res 63, 23882392.
235Challa A, Rao DR, Chawan CB, et al. (1997) Bifidobacterium longum and lactulose suppress azoxymethane-induced colonic aberrant crypt foci in rats. Carcinogenesis 18, 517521.
236Hsu CK, Liao JW, Chung YC, et al. (2004) Xylooligosaccharides and fructooligosaccharides affect the intestinal microbiota and precancerous colonic lesion development in rats. J Nutr 134, 15231528.
237Wijnands MV, Schoterman HC, Bruijntjes JB, et al. (2001) Effect of dietary galacto-oligosaccharides on azoxymethane-induced aberrant crypt foci and colorectal cancer in Fischer 344 rats. Carcinogenesis 22, 127132.
238Nakanishi S, Kataoka K, Kuwahara T, et al. (2003) Effects of high amylose maize starch and Clostridium butyricum on metabolism in colonic microbiota and formation of azoxymethane-induced aberrant crypt foci in the rat colon. Microbiol Immunol 47, 951958.
239Wijnands MV, Appel MJ, Hollanders VM, et al. (1999) A comparison of the effects of dietary cellulose and fermentable galacto-oligosaccharide, in a rat model of colorectal carcinogenesis: fermentable fibre confers greater protection than non-fermentable fibre in both high and low fat backgrounds. Carcinogenesis 20, 651656.
240Femia AP, Luceri C, Dolara P, et al. (2002) Antitumorigenic activity of the prebiotic inulin enriched with oligofructose in combination with the probiotics Lactobacillus rhamnosus and Bifidobacterium lactis on azoxymethane-induced colon carcinogenesis in rats. Carcinogenesis 23, 19531960.
241Pierre F, Perrin P, Champ M, et al. (1997) Short-chain fructo-oligosaccharides reduce the occurrence of colon tumors and develop gut-associated lymphoid tissue in Min mice. Cancer Res 57, 225228.
242Mutanen M, Pajari AM & Oikarinen SI (2000) Beef induces and rye bran prevents the formation of intestinal polyps in Apc(Min) mice: relation to beta-catenin and PKC isozymes. Carcinogenesis 21, 11671173.
243Pajari AM, Rajakangas J, Paivarinta E, et al. (2003) Promotion of intestinal tumor formation by inulin is associated with an accumulation of cytosolic beta-catenin in Min mice. Int J Cancer 106, 653660.
244Pool-Zobel BL (2005) Inulin-type fructans and reduction in colon cancer risk: review of experimental and human data. Br J Nutr 93, Suppl. 1, S73S90.
245Taper HS & Roberfroid M (1999) Influence of inulin and oligofructose on breast cancer and tumor growth. J Nutr 129, 1488S1491S.
246Taper HS & Roberfroid MB (2005) Possible adjuvant cancer therapy by two prebiotics-inulin or oligofructose. In vivo 19, 201204.
247Gill CI & Rowland IR (2002) Diet and cancer: assessing the risk. Br J Nutr 88, Suppl. 1, S73S87.
248Rafter J, Bennett M, Caderni G, et al. (2007) Dietary synbiotics reduce cancer risk factors in polypectomized and colon cancer patients. Am J Clin Nutr 85, 488496.
249Rowland IR, Bearne CA, Fischer R, et al. (1996) The effect of lactulose on DNA damage induced by DMH in the colon of human flora-associated rats. Nutr Cancer 26, 3747.
250Klinder A, Forster A, Caderni G, et al. (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, 144155.
251Perrin P, Pierre F, Patry Y, et al. (2001) Only fibres promoting a stable butyrate producing colonic ecosystem decrease the rate of aberrant crypt foci in rats. Gut 48, 5361.
252Hughes R & Rowland IR (2001) Stimulation of apoptosis by two prebiotic chicory fructans in the rat colon. Carcinogenesis 22, 4347.
253Commane DM, Shortt CT, Silvi S, et al. (2005) Effects of fermentation products of pro- and prebiotics on trans-epithelial electrical resistance in an in vitro model of the colon. Nutr Cancer 51, 102109.
254Roberfroid M (1993) Dietary fibers, inulin, and oligofructose: a review comparing their physiological effects. Crit Rev Food Sci Nutr 33, 103148.
255Roberfroid MB (1998) Prebiotics and synbiotics: concepts and nutritional properties. Br J Nutr 80, S197S202.
256Remesy C, Levrat MA, Gamet L, et al. (1993) Cecal fermentations in rats fed oligosaccharides (inulin) are modulated by dietary calcium level. Am J Physiol 264, G855G862.
257Ohta A, Ohtsuki M, Baba S, et al. (1995) Calcium and magnesium absorption from the colon and rectum are increased in rats fed fructooligosaccharides. J Nutr 125, 24172424.
258Lopez HW, Coudray C, Levrat-Verny MA, et al. (2000) Fructooligosaccharides enhance mineral apparent absorption and counteract the deleterious effects of phytic acid on mineral homeostasis in rats. J Nutr Biochem 11, 500508.
259Lutz T & Scharrer E (1991) Effect of short-chain fatty acids on calcium absorption by the rat colon. Exp Physiol 76, 615618.
260Ohta A, Motohashi Y, Sakai K, et al. (1998) Dietary fructooligosaccharides increase calcium absorption and levels of mucosal calbindin-D9k in the large intestine of gastrectomized rats. Scand J Gastroenterol 33, 10621068.
261Takasaki M, Inaba H, Ohta A, et al. (2000) Dietary short-chain fructooligosaccharides increase calbindin-D9k levels only in the large intestine in rats independent of dietary calcium deficiency or serum 1,25 dihydroxy vitamin D levels. Int J Vitam Nutr Res 70, 206213.
262Raschka L & Daniel H (2005) Mechanisms underlying the effects of inulin-type fructans on calcium absorption in the large intestine of rats. Bone 37, 728735.
263Scholz-Ahrens KE & Schrezenmeir J (2002) Inulin, oligofructose and mineral metabolism – experimental data and mechanism. Br J Nutr 87, Suppl. 2, S179S186.
264Heijnen AM, Brink EJ, Lemmens AG, et al. (1993) Ileal pH and apparent absorption of magnesium in rats fed on diets containing either lactose or lactulose. Br J Nutr 70, 747756.
265Beynen AC, Baas JC, Hoekemeijer PE, et al. (2002) Faecal bacterial profile, nitrogen excretion and mineral absorption in healthy dogs fed supplemental oligofructose. J Anim Physiol Anim Nutr (Berl) 86, 298305.
266Rayssiguier Y & Remesy C (1977) Magnesium absorption in the caecum of rats related to volatile fatty acids production. Ann Rech Vet 8, 105110.
267Leonhard-Marek S, Gabel G & Martens H (1998) Effects of short chain fatty acids and carbon dioxide on magnesium transport across sheep rumen epithelium. Exp Physiol 83, 155164.
268Delzenne N, Aertssens J, Verplaetse H, et al. (1995) Effect of fermentable fructo-oligosaccharides on mineral, nitrogen and energy digestive balance in the rat. Life Sci 57, 15791587.
269Yap KW, Mohamed S, Yazid AM, et al. (2005) Dose-response effects of inulin on the faecal fatty acids content and mineral absorption of formula-fed infants. Nutr Food Sci 35, 208219.
270van den Heuvel EG, Muys T, van Dokkum W, et al. (1999) Oligofructose stimulates calcium absorption in adolescents. Am J Clin Nutr 69, 544548.
271Griffin IJ, Davila PM & Abrams SA (2002) Non-digestible oligosaccharides and calcium absorption in girls with adequate calcium intakes. Br J Nutr 87, Suppl. 2, S187S191.
272Griffin IJ, Hicks PD, Heaney RP, et al. (2003) Enriched chicory inulin increases calcium absorption mainly in girls with lower calcium absorption. Nutr Res 23, 901909.
273van den Heuvel EG, Muijs T, Brouns F, et al. (2009) Short-chain fructo-oligosaccharides improve magnesium absorption in adolescent girls with a low calcium intake. Nutr Res 29, 229237.
274Abrams SA, Griffin IJ, Hawthorne KM, et al. (2005) A combination of prebiotic short- and long-chain inulin-type fructans enhances calcium absorption and bone mineralization in young adolescents. Am J Clin Nutr 82, 471476.
275Cashman KDA (2006) A prebiotic substance persistently enhances intestinal calcium absorption and increases bone mineralization in young adolescents. Nutr Rev 64, 189196.
276Abrams SA, Griffin IJ & Hawthorne KM (2007) Young adolescents who respond to an inulin-type fructan substantially increase total absorbed calcium and daily calcium accretion to the skeleton. J Nutr 137, 2524S2526S.
277Coudray C, Bellanger J, Castiglia-Delavaud C, et al. (1997) Effect of soluble or partly soluble dietary fibres supplementation on absorption and balance of calcium, magnesium, iron and zinc in healthy young men. Eur J Clin Nutr 51, 375380.
278van den Heuvel EG, Schaafsma G, Muys T, et al. (1998) Nondigestible oligosaccharides do not interfere with calcium and nonheme-iron absorption in young, healthy men. Am J Clin Nutr 67, 445451.
279Teuri U, Karkkainen M, Lamberg-Allardt C, et al. (1999) Addition of inulin to breakfast does not acutely affect serum ionized calcium and parathyroid hormone concentrations. Ann Nutr Metab 43, 356364.
280Lopez-Huertas E, Teucher B, Boza JJ, et al. (2006) Absorption of calcium from milks enriched with fructo-oligosaccharides, caseinophosphopeptides, tricalcium phosphate, and milk solids. Am J Clin Nutr 83, 310316.
281Abrams SA, Hawthorne KM, Aliu O, et al. (2007) An inulin-type fructan enhances calcium absorption primarily via an effect on colonic absorption in humans. J Nutr 137, 22082212.
282Ducros V, Arnaud J, Tahiri M, et al. (2005) Influence of short-chain fructo-oligosaccharides (sc-FOS) on absorption of Cu, Zn, and Se in healthy postmenopausal women. J Am Coll Nutr 24, 3037.
283Tahiri M, Tressol JC, Arnaud J, et al. (2001) Five-week intake of short-chain fructo-oligosaccharides increases intestinal absorption and status of magnesium in postmenopausal women. J Bone Miner Res 16, 21522160.
284Tahiri M, Tressol JC, Arnaud J, et al. (2003) Effect of short-chain fructooligosaccharides on intestinal calcium absorption and calcium status in postmenopausal women: a stable-isotope study. Am J Clin Nutr 77, 449457.
285van den Heuvel EG, Muijs T, van Dokkum W, et al. (1999) Lactulose stimulates calcium absorption in postmenopausal women. J Bone Miner Res 14, 12111216.
286van den Heuvel EG, Schoterman MH & Muijs T (2000) Transgalactooligosaccharides stimulate calcium absorption in postmenopausal women. J Nutr 130, 29382942.
287Adolphi B, Scholz-Ahrens KE, de Vrese M, et al. (2009) Short-term effect of bedtime consumption of fermented milk supplemented with calcium, inulin-type fructans and caseinphosphopeptides on bone metabolism in healthy, postmenopausal women. Eur J Nutr 48, 4553.
288Kim YY, Jang KH, Lee EY, et al. (2004) The effect of chicory fructan fiber on calcium absorption and bone metabolism in Korean postmenopausal women. Nutr Sci 7, 151157.
289Holloway L, Moynihan S, Abrams SA, et al. (2007) Effects of oligofructose-enriched inulin on intestinal absorption of calcium and magnesium and bone turnover markers in postmenopausal women. Br J Nutr 97, 365372.
290Dahl WJ, Whiting SJ, Isaac TM, et al. (2005) Effects of thickened beverages fortified with inulin on beverage acceptance, gastrointestinal function, and bone resorption in institutionalized adults. Nutrition 21, 308311.
291Levrat MA, Remesy C & Demigne C (1991) High propionic acid fermentations and mineral accumulation in the cecum of rats adapted to different levels of inulin. J Nutr 121, 17301737.
292Ohta A, Ohtuki M, Takizawa T, et al. (1994) Effects of fructooligosaccharides on the absorption of magnesium and calcium by cecectomized rats. Int J Vitam Nutr Res 64, 316323.
293Ellegard L, Andersson H & Bosaeus I (1997) Inulin and oligofructose do not influence the absorption of cholesterol, or the excretion of cholesterol, Ca, Mg, Zn, Fe, or bile acids but increases energy excretion in ileostomy subjects. Eur J Clin Nutr 51, 15.
294Scholz-Ahrens KE, Schaafsma G, van den Heuvel EG, et al. (2001) Effects of prebiotics on mineral metabolism. Am J Clin Nutr 73, 459S464S.
295Brommage R, Binacua C, Antille S, et al. (1993) Intestinal calcium absorption in rats is stimulated by dietary lactulose and other resistant sugars. J Nutr 123, 21862194.
296Scholz-Ahrens KE, Acil Y & Schrezenmeir J (2002) Effect of oligofructose or dietary calcium on repeated calcium and phosphorus balances, bone mineralization and trabecular structure in ovariectomized rats*. Br J Nutr 88, 365377.
297Kruger MC, Brown KE, Collett G, et al. (2003) The effect of fructooligosaccharides with various degrees of polymerization on calcium bioavailability in the growing rat. Exp Biol Med (Maywood) 228, 683688.
298Coudray C, Tressol JC, Gueux E, et al. (2003) Effects of inulin-type fructans of different chain length and type of branching on intestinal absorption and balance of calcium and magnesium in rats. Eur J Nutr 42, 9198.
299Coxam V (2005) Inulin-type fructans and bone health: state of the art and perspectives in the management of osteoporosis. Br J Nutr 93, Suppl. 1, S111S123.
300Setchell KD, Brown NM & Lydeking-Olsen E (2002) The clinical importance of the metabolite equol–a clue to the effectiveness of soy and its isoflavones. J Nutr 132, 35773584.
301Uehara M, Ohta A, Sakai K, et al. (2001) Dietary fructooligosaccharides modify intestinal bioavailability of a single dose of genistein and daidzein and affect their urinary excretion and kinetics in blood of rats. J Nutr 131, 787795.
302Ohta A, Uehara M, Sakai K, et al. (2002) A combination of dietary fructooligosaccharides and isoflavone conjugates increases femoral bone mineral density and equol production in ovariectomized mice. J Nutr 132, 20482054.
303Mathey J, Puel C, Kati-Coulibaly S, et al. (2004) Fructooligosaccharides maximize bone-sparing effects of soy isoflavone-enriched diet in the ovariectomized rat. Calcif Tissue Int 75, 169179.
304Devareddy L, Khalil DA, Korlagunta K, et al. (2006) The effects of fructo-oligosaccharides in combination with soy protein on bone in osteopenic ovariectomized rats. Menopause 13, 692699.
305Zafar TA, Weaver CM, Jones K, et al. (2004) Inulin effects on bioavailability of soy isoflavones and their calcium absorption enhancing ability. J Agric Food Chem 52, 28272831.
306Piazza C, Privitera MG, Melilli B, et al. (2007) Influence of inulin on plasma isoflavone concentrations in healthy postmenopausal women. Am J Clin Nutr 86, 775780.
307Ohta A, Baba S, Takizawa T, et al. (1994) Effects of fructooligosaccharides on the absorption of magnesium in the magnesium-deficient rat model. J Nutr Sci Vitaminol (Tokyo) 40, 171180.
308Ohta A, Ohtsuki M, Baba S, et al. (1995) Effects of fructooligosaccharides on the absorption of iron, calcium and magnesium in iron-deficient anemic rats. J Nutr Sci Vitaminol (Tokyo) 41, 281291.
309Kobayashi M, Nagatani Y, Magishi N, et al. (2006) Promotive effect of Shoyu polysaccharides from soy sauce on iron absorption in animals and humans. Int J Mol Med 18, 11591163.
310Cani PD & Delzenne NM (2009) The role of the gut microbiota in energy metabolism and metabolic disease. Curr Pharm Des 15, 15461558.
311Daubioul C, Rousseau N, Demeure R, et al. (2002) Dietary fructans, but not cellulose, decrease triglyceride accumulation in the liver of obese Zucker fa/fa rats. J Nutr 132, 967973.
312Cani PD, Possemiers S, van de WT, et al. (2009) Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut 58, 10911103.
313Chaudhri OB, Salem V, Murphy KG, et al. (2008) Gastrointestinal satiety signals. Annu Rev Physiol 70, 239255.
314Druce MR, Small CJ & Bloom SR (2004) Minireview: gut peptides regulating satiety. Endocrinology 145, 26602665.
315Wynne K, Stanley S, McGowan B, et al. (2005) Appetite control. J Endocrinol 184, 291318.
316Knauf C, Cani PD, Perrin C, et al. (2005) Brain glucagon-like peptide-1 increases insulin secretion and muscle insulin resistance to favor hepatic glycogen storage. J Clin Invest 115, 35543563.
317Cani PD, Dewever C & Delzenne NM (2004) Inulin-type fructans modulate gastrointestinal peptides involved in appetite regulation (glucagon-like peptide-1 and ghrelin) in rats. Br J Nutr 92, 521526.
318Delzenne NM, Cani PD, Daubioul C, et al. (2005) Impact of inulin and oligofructose on gastrointestinal peptides. Br J Nutr 93, Suppl. 1, S157S161.
319Urias-Silvas JE, Cani PD, Delmee E, et al. (2008) Physiological effects of dietary fructans extracted from Agave tequilana Gto. and Dasylirion spp. Br J Nutr 99, 254261.
320Cani PD, Knauf C, Iglesias MA, et al. (2006) Improvement of glucose tolerance and hepatic insulin sensitivity by oligofructose requires a functional glucagon-like peptide 1 receptor. Diabetes 55, 14841490.
321Reimer RA & Russell JC (2008) Glucose tolerance, lipids, and GLP-1 secretion in JCR:LA-cp rats fed a high protein fiber diet. Obesity (Silver Spring) 16, 4046.
322Maurer AD, Chen Q, McPherson C, et al. (2009) Changes in satiety hormones and expression of genes involved in glucose and lipid metabolism in rats weaned onto diets high in fibre or protein reflect susceptibility to increased fat mass in adulthood. J Physiol 587, 679691.
323Cani PD, Hoste S, Guiot Y, et al. (2007) Dietary non-digestible carbohydrates promote L-cell differentiation in the proximal colon of rats. Br J Nutr 98, 3237.
324Cani PD, Joly E, Horsmans Y, et al. (2006) Oligofructose promotes satiety in healthy human: a pilot study. Eur J Clin Nutr 60, 567572.
325Archer BJ, Johnson SK, Devereux HM, et al. (2004) Effect of fat replacement by inulin or lupin-kernel fibre on sausage patty acceptability, post-meal perceptions of satiety and food intake in men. Br J Nutr 91, 591599.
326Piche T, des Varannes SB, Sacher-Huvelin S, et al. (2003) Colonic fermentation influences lower esophageal sphincter function in gastroesophageal reflux disease. Gastroenterology 124, 894902.
327Cani PD, Lecourt E, Dewulf EM, et al. (2009) Gut microbiota fermentation of prebiotics increases satietogenic and incretin gut peptide production with consequences for appetite sensation and glucose response after a meal. Am J Clin Nutr 90, 12361243.
328Abrams SA, Griffin IJ, Hawthorne KM, et al. (2007) Effect of prebiotic supplementation and calcium intake on body mass index. J Pediatr 151, 293298.
329Genta S, Cabrera W, Habib N, et al. (2009) Yacon syrup: beneficial effects on obesity and insulin resistance in humans. Clin Nutr 28, 182187.
330Parnell JA & Reimer RA (2009) Weight loss during oligofructose supplementation is associated with decreased ghrelin and increased peptide YY in overweight and obese adults. Am J Clin Nutr 89, 17511759.
331Peters HP, Boers HM, Haddeman E, et al. (2009) No effect of added beta-glucan or of fructooligosaccharide on appetite or energy intake. Am J Clin Nutr 89, 5863.
332Busserolles J, Gueux E, Rock E, et al. (2003) Oligofructose protects against the hypertriglyceridemic and pro-oxidative effects of a high fructose diet in rats. J Nutr 133, 19031908.
333Kok NN, Taper HS & Delzenne NM (1998) Oligofructose modulates lipid metabolism alterations induced by a fat-rich diet in rats. J Appl Toxicol 18, 4753.
334Cani PD, Neyrinck AM, Maton N, et al. (2005) Oligofructose promotes satiety in rats fed a high-fat diet: involvement of glucagon-like peptide-1. Obes Res 13, 10001007.
335Delmee E, Cani PD, Gual G, et al. (2006) Relation between colonic proglucagon expression and metabolic response to oligofructose in high fat diet-fed mice. Life Sci 79, 10071013.
336Cani PD, Daubioul CA, Reusens B, et al. (2005) Involvement of endogenous glucagon-like peptide-1(7-36) amide on glycaemia-lowering effect of oligofructose in streptozotocin-treated rats. J Endocrinol 185, 457465.
337Perrin M IV, archesini M, Rochat FC, et al. (2003) Oligofructose does not affect the development of Type 1 diabetes mellitus induced by dietary proteins in the diabetes-prone BB rat model. Diab Nutr Metabol 16, 94101.
338Respondek F, Swanson KS, Belsito KR, et al. (2008) Short-chain fructooligosaccharides influence insulin sensitivity and gene expression of fat tissue in obese dogs. J Nutr 138, 17121718.
339Luo J, Rizkalla SW, Alamowitch C, et al. (1996) Chronic consumption of short-chain fructooligosaccharides by healthy subjects decreased basal hepatic glucose production but had no effect on insulin-stimulated glucose metabolism. Am J Clin Nutr 63, 939945.
340Luo J, Van Yperselle M, Rizkalla SW, et al. (2000) Chronic consumption of short-chain fructooligosaccharides does not affect basal hepatic glucose production or insulin resistance in type 2 diabetics. J Nutr 130, 15721577.
341Giacco R, Clemente G, Luongo D, et al. (2004) Effects of short-chain fructo-oligosaccharides on glucose and lipid metabolism in mild hypercholesterolaemic individuals. Clin Nutr 23, 331340.
342Delzenne NM & Cani PD (2008) Gut microflora is a key player in host energy homeostasis. Med Sci (Paris) 24, 505510.
343Delzenne NM & Williams CM (2002) Prebiotics and lipid metabolism. Curr Opin Lipidol 13, 6167.
344Daubioul CA, Taper HS, De Wispelaere LD, et al. (2000) Dietary oligofructose lessens hepatic steatosis, but does not prevent hypertriglyceridemia in obese zucker rats. J Nutr 130, 13141319.
345Morand C, Remesy C & Demigne C (1993) Fatty acids are potent modulators of lactate utilization in isolated hepatocytes from fed rats. Am J Physiol 264, E816E823.
346Delzenne NM, Daubioul C, Neyrinck A, et al. (2002) Inulin and oligofructose modulate lipid metabolism in animals: review of biochemical events and future prospects. Br J Nutr 87, S255S259.
347Sakakibara S, Yamauchi T, Oshima Y, et al. (2006) Acetic acid activates hepatic AMPK and reduces hyperglycemia in diabetic KK-A(y) mice. Biochem Biophys Res Commun 344, 597604.
348Levrat MA, Favier ML, Moundras C, et al. (1994) Role of dietary propionic acid and bile acid excretion in the hypocholesterolemic effects of oligosaccharides in rats. J Nutr 124, 531538.
349Fiordaliso M, Kok N, Desager JP, et al. (1995) Dietary oligofructose lowers triglycerides, phospholipids and cholesterol in serum and very low density lipoproteins of rats. Lipids 30, 163167.
350Rault-Nania MH, Gueux E, Demougeot C, et al. (2006) Inulin attenuates atherosclerosis in apolipoprotein E-deficient mice. Br J Nutr 96, 840844.
351Fava F, Lovegrove JA, Gitau R, et al. (2006) The gut microbiota and lipid metabolism: implications for human health and coronary heart disease. Curr Med Chem 13, 30053021.
352Trautwein EA, Forgbert K, Rieckhoff D, et al. (1999) Impact of beta-cyclodextrin and resistant starch on bile acid metabolism and fecal steroid excretion in regard to their hypolipidemic action in hamsters. Biochim Biophys Acta Mol Cell Biol Lipids 1437, 112.
353Adam A, Levrat-Verny MA, Lopez HW, et al. (2001) Whole wheat and triticale flours with differing viscosities stimulate cecal fermentations and lower plasma and hepatic lipids in rats. J Nutr 131, 17701776.
354van Meer H, Boehm G, Stellaard F, et al. (2008) Prebiotic oligosaccharides and the enterohepatic circulation of bile salts in rats. Am J Physiol Gastrointest Liver Physiol 294, G540G547.
355Brighenti F (2007) Dietary fructans and serum triacylglycerols: a meta-analysis of randomized controlled trials. J Nutr 137, 2552S2556S.
356Diraison F, Moulin P & Beylot M (2003) Contribution of hepatic de novo lipogenesis and reesterification of plasma non esterified fatty acids to plasma triglyceride synthesis during non-alcoholic fatty liver disease. Diabet Metab 29, 478485.
357Daubioul CA, Horsmans Y, Lambert P, et al. (2005) Effects of oligofructose on glucose and lipid metabolism in patients with nonalcoholic steatohepatitis: results of a pilot study. Eur J Clin Nutr 59, 723726.
358Cani PD & Delzenne NM (2009) Interplay between obesity and associated metabolic disorders: new insights into the gut microbiota. Curr Opin Pharmacol 9, 737743.
359Cani PD, Amar J, Iglesias MA, et al. (2007) Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 56, 17611772.
360Turnbaugh PJ, Backhed F, Fulton L, et al. (2008) Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe 3, 213223.
361Cani PD, Neyrinck AM, Fava F, et al. (2007) Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia 50, 23742383.
362Cani PD, Bibiloni R, Knauf C, et al. (2008) Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 57, 14701481.
363Waldram A, Holmes E, Wang Y, et al. (2009) Top-down systems biology modeling of host metabotype-microbiome associations in obese rodents. J Proteome Res 8, 23612375.
364Wang Z, Xiao G, Yao Y, et al. (2006) The role of bifidobacteria in gut barrier function after thermal injury in rats. J Trauma 61, 650657.
365Griffiths EA, Duffy LC, Schanbacher FL, et al. (2004) In vivo effects of bifidobacteria and lactoferrin on gut endotoxin concentration and mucosal immunity in Balb/c mice. Dig Dis Sci 49, 579589.
366Wang ZT, Yao YM, Xiao GX, et al. (2004) Risk factors of development of gut-derived bacterial translocation in thermally injured rats. World J Gastroenterol 10, 16191624.
367Ruan X, Shi H, Xia G, et al. (2007) Encapsulated bifidobacteria reduced bacterial translocation in rats following hemorrhagic shock and resuscitation. Nutrition 23, 754761.
368Keenan MJ, Zhou J, McCutcheon KL, et al. (2006) Effects of resistant starch, a non-digestible fermentable fiber, on reducing body fat. Obesity (Silver Spring) 14, 15231534.
369Zhou J, Martin RJ, Tulley RT, et al. (2008) Dietary resistant starch upregulates total GLP-1 and PYY in a sustained day-long manner through fermentation in rodents. Am J Physiol Endocrinol Metab 295, E1160E1166.
370Juntunen KS, Niskanen LK, Liukkonen KH, et al. (2002) Postprandial glucose, insulin, and incretin responses to grain products in healthy subjects. Am J Clin Nutr 75, 254262.
371Adam TC & Westerterp-Plantenga MS (2005) Nutrient-stimulated GLP-1 release in normal-weight men and women. Horm Metab Res 37, 111117.
372Nilsson AC, Ostman EM, Holst JJ, et al. (2008) Including indigestible carbohydrates in the evening meal of healthy subjects improves glucose tolerance, lowers inflammatory markers, and increases satiety after a subsequent standardized breakfast. J Nutr 138, 732739.
373Gao Z, Yin J, Zhang J, et al. (2009) Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes 58, 15091517.
374Kalliomaki M, Collado MC, Salminen S, et al. (2008) Early differences in fecal microbiota composition in children may predict overweight. Am J Clin Nutr 87, 534538.
375Lundell AC, Adlerberth I, Lindberg E, et al. (2007) Increased levels of circulating soluble CD14 but not CD83 in infants are associated with early intestinal colonization with Staphylococcus aureus. Clin Exp Allergy 37, 6271.
376Gronlund MM, Gueimonde M, Laitinen K, et al. (2007) Maternal breast-milk and intestinal bifidobacteria guide the compositional development of the Bifidobacterium microbiota in infants at risk of allergic disease. Clin Exp Allergy 37, 17641772.
377Salminen S, Bouley C, Boutron-Ruault MC, et al. (1998) Functional food science and gastrointestinal physiology and function. Br J Nutr 80, Suppl. 1, S147S171.
378Salminen S, Gibson GR, McCartney AL, et al. (2004) Influence of mode of delivery on gut microbiota composition in seven year old children. Gut 53, 13881389.
379Salminen S & Isolauri E (2008) Opportunities for improving the health and nutrition of the human infant by probiotics. Nestle Nutr Workshop Ser Pediatr Program 62, 223233.
380Salminen S, Collado MC, Isolauri E, et al. (2009) Microbial-host interactions: selecting the right probiotics and prebiotics for infants. Nestle Nutr Workshop Ser Pediatr Program 64, 201213.
381Bellisle F, Diplock AT, Hornstra G, et al. (1998) Functional food science in Europe. Br J Nutr 80, S1193.
382Walter J, Tannock GW, Tilsala-Timisjarvi A, et al. (2000) Detection and identification of gastrointestinal Lactobacillus species by using denaturing gradient gel electrophoresis and species-specific PCR primers. Appl Environ Microbiol 66, 297303.
383Satokari RM, Vaughan EE, Akkermans AD, et al. (2001) Bifidobacterial diversity in human feces detected by genus-specific PCR and denaturing gradient gel electrophoresis. Appl Environ Microbiol 67, 504513.
384Heilig HG, Zoetendal EG, Vaughan EE, et al. (2002) Molecular diversity of Lactobacillus spp. and other lactic acid bacteria in the human intestine as determined by specific amplification of 16S ribosomal DNA. Appl Environ Microbiol 68, 114123.
385Shen J, Zhang B, Wei G, et al. (2006) Molecular profiling of the Clostridium leptum subgroup in human fecal microflora by PCR-denaturing gradient gel electrophoresis and clone library analysis. Appl Environ Microbiol 72, 52325238.
386Vanhoutte T, de Preter V, De Brandt E, et al. (2006) Molecular monitoring of the fecal microbiota of healthy human subjects during administration of lactulose and Saccharomyces boulardii. Appl Environ Microbiol 72, 59905997.
387Kruse HP, Kleessen B & Blaut M (1999) Effects of inulin on faecal bifidobacteria in human subjects. Br J Nutr 82, 375382.
388Bouhnik Y, Vahedi K, Achour L, et al. (1999) Short-chain fructo-oligosaccharide administration dose–dependently increases fecal bifidobacteria in healthy humans. J Nutr 129, 113116.
389Gibson GR, Beatty ER, Wang X, et al. (1995) Selective stimulation of bifidobacteria in the human colon by oligofructose and inulin. Gastroenterology 108, 975982.
390Kleessen B, Sykura B, Zunft HJ, et al. (1997) The effects of inulin and lactose on fecal microflora, microbial activity, and bowel habit in elderly constipated persons. Am J Clin Nutr 65, 13971402.
391Tuohy KM, Kolida S, Lustenberger AM, et al. (2001) The prebiotic effects of biscuits containing partially hydrolysed guar gum and fructo-oligosaccharides – a human volunteer study. Br J Nutr 86, 341348.
392Buddington RK, Williams CH, Chen SC, et al. (1996) Dietary supplement of neosugar alters the fecal flora and decreases activities of some reductive enzymes in human subjects. Am J Clin Nutr 63, 709716.
393Menne E, Guggenbuhl N & Roberfroid M (2000) Fn-type chicory inulin hydrolysate has a prebiotic effect in humans. J Nutr 130, 11971199.
394Teuri U, Korpela R, Saxelin M, et al. (1998) Increased fecal frequency and gastrointestinal symptoms following ingestion of galacto-oligosaccharide-containing yogurt. J Nutr Sci Vitaminol (Tokyo) 44, 465471.
395Moro G, Minoli I, Mosca M, et al. (2002) Dosage-related bifidogenic effects of galacto- and fructooligosaccharides in formula-fed term infants. J Pediatr Gastroenterol Nutr 34, 291295.
396Bouhnik Y, Raskine L, Simoneau G, et al. (2004) The capacity of nondigestible carbohydrates to stimulate fecal bifidobacteria in healthy humans: a double-blind, randomized, placebo-controlled, parallel-group, dose-response relation study. Am J Clin Nutr 80, 1658.
397Bouhnik Y, Achour L, Paineau D, et al. (2007) Four-week short chain fructo-oligosaccharides ingestion leads to increasing fecal bifidobacteria and cholesterol excretion in healthy elderly volunteers. Nutrition 6, 4246.
398Kleessen B, Schwarz S, Boehm A, et al. (2007) Jerusalem artichoke and chicory inulin in bakery products affect faecal microbiota of healthy volunteers 2. Br J Nutr 98, 540549.
399Tuohy KM, Finlay RK, Wynne AG, et al. (2001) A human volunteer study on the prebiotic effects of HP-inulin – Faecal bacteria enumerated using fluorescent in situ hybridisation (FISH). Anaerobe 7, 113118.
400Williams CH, Witherly SA & Buddington RK (1994) Influence of dietary neosugar on selected bacterial groups of the human fecal microbiota. Microbial Ecol Health Dis 7, 9197.
401Depeint F, Tzortzis G, Vulevic J, et al. (2008) Prebiotic evaluation of a novel galactooligosaccharide mixture produced by the enzymatic activity of Bifidobacterium bifidum NCIMB 41171, in healthy humans: a randomized, double-blind, crossover, placebo-controlled intervention study. Am J Clin Nutr 87, 785791.
402Bakker-Zierikzee AM, Alles MS, Knol J, et al. (2005) Effects of infant formula containing a mixture of galacto- and fructo-oligosaccharides or viable Bifidobacterium animalis on the intestinal microflora during the first 4 months of life. Br J Nutr 94, 783790.
403Mattö J, Maunuksela L, Kajander K, et al. (2005) Composition and temporal stability of gastrointestinal microbiota in irritable bowel syndrome – a longitudinal study in IBS and control subjects. FEMS Immunol Med Microbiol 43, 213222.
404Walker AR (1987) Dietary fibre, minerals and vitamins. Int J Obes 11, Suppl. 1, 4556.
405Roberfroid M (1997) Dietary Fiber in Health and Disease. New York: Plenum Press.
406Coudray C & Fairweather-Tait SJ (1998) Do oligosaccharides affect the intestinal absorption of calcium in humans? Am J Clin Nutr 68, 921923.
407Schaafsma G (1997) Bioavailability of calcium and magnesium. Eur J Clin Nutr 51, Suppl. 1, S13S16.
408Fairweather-Tait SJ & Johnson IT (1999) Bioavailability of minerals. In Colonic Microbiota, Nutrition and Health, pp. 233244 [Gibson GR and Roberfroid MB, editors]. Dordrecht: Kluwer Academic Publishers.
409Carabin IG & Flamm WG (1999) Evaluation of safety of inulin and oligofructose as dietary fiber. Regul Toxicol Pharmacol 30, 268282.
410Franck A (2000) Prebiotics and calcium absorption. In Functional Foods, pp. 108113 [Angus F and Miller C, editors]. Surrey: Leatherhead Publishing.
411van Dokkum W & van den Heuvel E (2001) Non digestible oligosaccharides and mineral absorption. In Handbook of Dietary Fiber, pp. 259267 [Cho S and Dreher ML, editors]. New York: CRC Press.
412Roberfroid M (2002) Functional foods: concepts and application to inulin and oligofructose. Br J Nutr 87, S139S143.
413Cashman KD (2002) Calcium intake, calcium bioavailability and bone health. Br J Nutr 87, Suppl. 2, S169S177.
414Kaur N & Gupta AK (2002) Applications of inulin and oligofructose in health and nutrition. J Biosci 27, 703714.
415Cashman KD (2002) Prebiotics and calcium bioavailability. In Probiotics and Prebiotics: Where Are We going?, pp. 149171 [Tannock GW, editor]. Wymondham: Caister Academic Press.
416Bongers A & van den Heuvel EGHM (2003) Prebiotics and the bioavailability of minerals and trace elements. Food Rev Int 19, 397422.
417Cashman KD (2003) Prebiotics and calcium bioavailability. Curr Issues Intest Microbiol 4, 2132.
418Caers W (2003) The role of prebiotic fibres in the process of calcium absorption. Dietary Fibre Congress – Conference Proceedings 46, .
419Coudray C, Demigne C & Rayssiguier Y (2003) Effects of dietary fibers on magnesium absorption in animals and humans. J Nutr 133, 14.
420Coudray C (2004) Dietary fibers and mineral absorption: the case of magnesium. Agro Food Industry Hi-Tech 15, 4041, Special highlight: Prebiotics & Probiotics.
421Weaver CM (2005) Inulin, oligofructose and bone health: experimental approaches and mechanisms. Br J Nutr 93, Suppl. 1, S99103.
422Franck A (2006) Oligofructose-enriched inulin stimulates calcium absorption and bone mineralisation. Nutr Bull 31, 341345.
423Bosscher D, Loo JV & Franck A (2006) Inulin and oligofructose as functional ingredients to improve bone mineralization. Int Dairy J 10921097.
424Coxam V (2007) Current data with inulin-type fructans and calcium, targeting bone health in adults. J Nutr 137, 2527S2533S.
425Scholz-Ahrens KE & Schrezenmeir J (2007) Inulin and oligofructose and mineral metabolism: the evidence from animal trials. J Nutr 137, 2513S2523S.
426Scholz-Ahrens KE, Ade P, Marten B, et al. (2007) Prebiotics, probiotics, and synbiotics affect mineral absorption, bone mineral content, and bone structure. J Nutr 137, 838S846S.
427Alexiou H & Franck A (2008) Prebiotic inulin-type fructans: nutritional benefits beyond dietary fibre source. Beneo-Orafti Nutr Bull 33, 227233.
428Gibson GR & Delzenne NM (2008) Inulin and oligofructose. Nutr Today 43, 5459.
429de Vrese M & Schrezenmeir J (2008) Probiotics, prebiotics, and synbiotics. Adv Biochem Eng Biotechnol 111, 166.
430Griffin IJ & Abrams SA (2007) Effects of prebiotics on mineral absorption: mechanisms of action. In Handbook of Prebiotics, pp. 93103 [Gibson GR and Roberfroid M, editors]. London: CRC Press.
431Hawthorne KM & Abrams SA (2007) Prebiotics and the absorption of minerals:a review of experimental and human data. In Handbook of Prebiotics, pp. 105113 [Gibson GR and Roberfroid M, editors]. London: CRC Press.
432Kelly G (2009) Inulin-type prebiotics: a review (Part 2). Altern Med Rev 14, 3655.
433de Vrese M (2009) Health benefits of probiotics and prebiotics in women. Menopause Int 15, 3540.
434Chonan O, Matsumoto K & Watanuki M (1995) Effect of galactooligosaccharides on calcium absorption and preventing bone loss in ovariectomized rats. Biosci Biotechnol Biochem 59, 236239.
435Takahara S, Morohashi T, Sano T, et al. (2000) Fructooligosaccharide consumption enhances femoral bone volume and mineral concentrations in rats. J Nutr 130, 17921795.
436Richardson JE, Verghese M, Walker LT, et al. (2002) Effects of prebiotics on bone mineralisation in Fisher 344 male weabing rats. IFT USA.
437Zafar TA, Weaver CM, Zhao Y, et al. (2004) Nondigestible oligosaccharides increase calcium absorption and suppress bone resorption in ovariectomized rats. J Nutr 134, 399402.
438Mitamura R & Hara H (2005) Prolonged feeding of difructose anhydride III increases strength and mineral concentrations of the femur in ovariectomized rats. Br J Nutr 94, 268274.
439Mitamura R & Hara H (2006) Ingestion of difructose anhydride III partially restores calcium absorption impaired by vitamin D and estrogen deficiency in rats. Eur J Nutr 45, 242249.
440Nzeusseu A, Dienst D, Haufroid V, et al. (2006) Inulin and fructo-oligosaccharides differ in their ability to enhance the density of cancellous and cortical bone in the axial and peripheral skeleton of growing rats. Bone 38, 394399.
441Lobo AR, Colli C & Filisetti TMCC (2006) Fructooligosaccharides improve bone mass and biomechanical properties in rats. Nutr Res 26, 413420.
442Jamieson JA, Ryz NR, Taylor CG, et al. (2008) Dietary long-chain inulin reduces abdominal fat but has no effect on bone density in growing female rats. Br J Nutr 100, 451459.
443Demigne C, Jacobs H, Moundras C, et al. (2008) Comparison of native or reformulated chicory fructans, or non-purified chicory, on rat cecal fermentation and mineral metabolism. Eur J Nutr 47, 366374.
444Lobo AR, Filho JM, Alvares EP, et al. (2009) Effects of dietary lipid composition and inulin-type fructans on mineral bioavailability in growing rats. Nutrition 25, 216225.
445Rondon LJ, Rayssiguier Y & Mazur A (2008) Dietary inulin in mice stimulates Mg2+ absorption and modulates TRPM6 and TRPM7 expression in large intestine and kidney. Magnes Res 21, 224231.
446Chonan O & Watanuki M (1995) Effect of galactooligosaccharides on calcium absorption in rats. J Nutr Sci Vitaminol (Tokyo) 41, 95104.
447Yanahira S, Morita M, Aoe S, et al. (1997) Effects of lactitol-oligosaccharides on calcium and magnesium absorption in rats. J Nutr Sci Vitaminol (Tokyo) 43, 123132.
448Morohashi T, Sano T, Ohta A, et al. (1998) True calcium absorption in the intestine is enhanced by fructooligosaccharide feeding in rats. J Nutr 128, 18151818.
449Younes H, Coudray C, Bellanger J, et al. (2001) Effects of two fermentable carbohydrates (inulin and resistant starch) and their combination on calcium and magnesium balance in rats. Br J Nutr 86, 479485.
450Mitamura R, Hara H, Aoyama Y, et al. (2002) Supplemental feeding of difructose anhydride III restores calcium absorption impaired by ovariectomy in rats. J Nutr 132, 33873393.
451Asvarujanon P, Ishizuka S & Hara H (2005) Promotive effects of non-digestible disaccharides on rat mineral absorption depend on the type of saccharide. Nutrition 21, 10251035.
452Coudray C, Feillet-Coudray C, Tressol JC, et al. (2005) Stimulatory effect of inulin on intestinal absorption of calcium and magnesium in rats is modulated by dietary calcium intakes short- and long-term balance studies. Eur J Nutr 44, 293302.
453Coudray C, Rambeau M, Feillet-Coudray C, et al. (2005) Dietary inulin intake and age can significantly affect intestinal absorption of calcium and magnesium in rats: a stable isotope approach. Nutr J 4, 29.
454Shiga K, Nishimukai M, Tomita F, et al. (2006) Ingestion of difructose anhydride III, a non-digestible disaccharide, prevents gastrectomy-induced iron malabsorption and anemia in rats. Nutrition 22, 786793.
455Coudray C, Feillet-Coudray C, Gueux E, et al. (2006) Dietary inulin intake and age can affect intestinal absorption of zinc and copper in rats. J Nutr 136, 117122.
456Azorin-Ortuno M, Urban C, Ceron JJ, et al. (2009) Effect of low inulin doses with different polymerisation degree on lipid metabolism, mineral absorption, and intestinal microbiota in rats with fat-supplemented diet. Food Chem 113, 10581065.
457Klobukowski J, Modzelewska-Kapitula M & Kornacki K (2009) Calcium bioavailability from diets based on white cheese containing probiotics or synbiotics in short-time study in rats. Pakistan J Nutr 8, 933936.
458Wang Y, Zeng T, Wang SE, et al. (2010) Fructo-oligosaccharides enhance the mineral absorption and counteract the adverse effects of phytic acid in mice. Nutrition 26, 305311.
459Mathey J, Lamothe V, Benneteau-Pelissero C, et al. (2008) Improvement of bone-sparing effect of soy isoflavones by pre-and probiotics in postmenopausal women. Clinl Med Women's Health 1, 1523.
460Sakaguchi E, Sakoda C & Toramaru Y (1998) Caecal fermentation and energy accumulation in the rat fed on indigestible oligosaccharides. Br J Nutr 80, 469476.
461Juskiewicz J, Jankowski J, Zdunczyk Z, et al. (2006) Performance and gastrointestinal tract metabolism of turkeys fed diets with different contents of fructooligosaccharides. Poult Sci 85, 886.
462Zdunczyk Z, Juskiewicz J & Estrella I (2006) Cecal parameters of rats fed diets containing grapefruit polyphenols and inulin as single supplements or in a combination. Nutrition 22, 898.
463Sugatani J, Wada T, Osabe M, et al. (2006) Dietary inulin alleviates hepatic steatosis and xenobiotics-induced liver injury in rats fed a high-fat and high-sucrose diet: association with the suppression of hepatic cytochrome P450 and hepatocyte nuclear factor 4alpha expression. Drug Metab Dispos 34, 16771687.