Hostname: page-component-cd9895bd7-jn8rn Total loading time: 0 Render date: 2024-12-23T11:11:48.988Z Has data issue: false hasContentIssue false

The SYNCAN project: goals, set-up, first results and settings of the human intervention study

Published online by Cambridge University Press:  08 March 2007

Jan Van Loo*
Affiliation:
Orafti, Aandorenstraat 1, B3300, Tienen, Belgium
Yvonne Clune
Affiliation:
Departments of Microbiology and Medicine, Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland
Mary Bennett
Affiliation:
Departments of Microbiology and Medicine, Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland
John Kevin Collins
Affiliation:
Departments of Microbiology and Medicine, Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland
*
*Corresponding author: Dr Jan Van Loo, fax +32 16 801 359, email [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Experimental evidence on the anticancer properties of dietary prebiotics such as chicory inulin and oligofructose and dietary probiotics has accumulated in recent years. Various experimental models ranging from chemoprevention studies, tumour implantation models to genetically modified mice models, etc. have systematically shown the protective effects of these food ingredients. In some studies it appeared that synbiotics (combination of pre- and probiotics) exerted synergistic activity against processes of carcinogenesis. The logical next step in research was to find out if these observations also would be valid for human volunteers. This was the principal goal of the EU-sponsored SYNCAN project (QLK1-1999-346) which involved the integration of an in vitro study to select the most suitable synbiotic preparation, the application of this synbiotic in an in vivo rat model of chemically induced colon cancer, and, as the heart of the project, the investigation of the synbiotic effects in a human intervention study. The in vitro tests consisted of fermentation studies where the interaction of pre- and probiotics was studied. Cell-free supernatants were generated from various synbiotic combinations fermented by faecal slurry, which were then used to optimise a series of bioassays. In the rat study the anticarcinogenic effect of prebiotics and synbiotics but not of probiotics was demonstrated. Using tissue samples generated in this model, attempts were made to gain a better insight into the mechanisms underlying cancer development. The human intervention study consisted of two groups of volunteers. One group was composed of people at high risk (polypectomised subjects) for colon cancer and the other of volunteers (colon cancer subjects) who had previously undergone ‘curative resection‘ for colon cancer but were not currently receiving treatment. The present paper describes the experimental design of the SYNCAN study, and demonstrates a functional effect of the synbiotic preparation (probiotic survival during gastrointestinal transit and modification of the intestinal flora). Detailed experimental outcome of the human intervention study will be reported elsewhere.

Type
Research Article
Copyright
Copyright © The Nutrition Society 2005

References

Bolognani, F, Rumney, CJ, Pool-Zobel, BL & Rowland, IR (2001) Effect of lactobacilli, bifidobacteria and inulin on the formation of aberrant crypt foci in rats. Eur J Nutr 40, 293300.CrossRefGoogle ScholarPubMed
Dunne, C, Murphy, L & Flynn, S (1999) Probiotics: from myth to reality. Demonstration of functionality in animal models of disease and in human clinical trials. Antonie Van Leeuwenhoek 76, 279292.CrossRefGoogle ScholarPubMed
Dunne, C, O'Mahony, L & Murphy, L (2001) In vitro selection criteria for probiotic bacteria of human origin: correlation with in vivo findings. Am J Clin Nutr 73, Suppl.386S392S.CrossRefGoogle ScholarPubMed
Femia, AP, Luceri, C, Dolara, P, Giannini, A, Biggeri, A, Salvadori, M, Clune, Y, Collins, KJ, Paglierani, M & Caderni, G (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.CrossRefGoogle ScholarPubMed
Gallaher, DD, Stallings, WH, Blessing, LL, Busta, FF & Brady, LJ (1996) Probiotics, cecal microflora, and aberrant crypts in the rat colon. J Nutr 126, 13621371.CrossRefGoogle ScholarPubMed
Hartemink, R, Kok, BJ, Weenk, GH & Rombouts, FM (1996) Raffinose-Bifidobacterium (RB) agar, a new selective medium for bifidobacteria. J Microbiol Methods 27, 3343.CrossRefGoogle Scholar
Klinder, A, Förster, 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, 144155.CrossRefGoogle ScholarPubMed
Klinder, A, Gietl, E, Hughes, R, Jonkers, N, Pistoli, S, Gibson, G, Rowland, I, Van Loo, J, Pool-Zobel, B (2003) Gut fermentation products of inulin-derived prebiotics inhibit markers of tumor progression in human colon tumor cells. J Cancer Prev 1, 1932.Google Scholar
Kruse, HP, Kleessen, B & Blaut, M (1999) Effects of inulin on faecal bifidobacteria in human subjects. Br J Nutr 82, 375382.CrossRefGoogle ScholarPubMed
Kulkarni, N & Reddy, BS (1994) Inhibitory effect of Bifidobacterium longum cultures on the azoxymethane-induced aberrant crypt foci formation and fecal bacterial beta-glucuronidase. Proc Soc Exp Biol Med 207, 278283.CrossRefGoogle ScholarPubMed
McBain, AJ & Macfarlane, GT (1997) Investigations of bifidobacterial ecology and oligosaccharide metabolism in a three-stage compound continuous culture system. Scand J Gastroenterol Suppl 22, 232240.Google Scholar
O'Mahony, L, Feeney, M, O'Halloran, S, Murphy, L, Kiely, B, Fitzgibbon, J, Lee, G, O'Sullivan, G, Shanahan, F & Collins, JK (2001) Probiotic impact on microbial flora, inflammation and tumour development in IL-10 knockout mice. Aliment Pharmacol Ther 15, 219225.CrossRefGoogle ScholarPubMed
Pierre, F, Perrin, P, Champ, M, Bornet, F, Meflah, K & Menanteau, J (1997) Short-chain fructo-oligosaccharides reduce the occurrence of colon tumors and develop gut-associated lymphoid tissue in Min mice. Cancer Res 57, 225228.Google ScholarPubMed
Rao, VA (2001) The prebiotic properties of oligofructose at low intake levels. Nutr Res 21, 843848.CrossRefGoogle Scholar
Reddy, BS, Hamid, R & Rao, CV (1997) Effect of dietary oligofructose and inulin on colonic preneoplastic aberrant crypt foci inhibition. Carcinogenesis 18, 13711374.CrossRefGoogle ScholarPubMed
Roller, M, Rechkemmer, G & Watzl, B (2004a) 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.CrossRefGoogle ScholarPubMed
Roller, M, Femia, AP, Caderni, G, Rechkemmer, G & Watzl, B (2004b) 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.CrossRefGoogle ScholarPubMed
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, 281285.CrossRefGoogle ScholarPubMed
Salminen, S, Bouley, C, Boutron-Ruault, MC, Cummings, JH, Franck, A, Gibson, GR, Isolauri, E, Moreau, MC, Roberfroid, M & Rowland, I (1998) Functional food science and gastrointestinal physiology and fucntion. Br J Nutr 80, S147S171Suppl. 1CrossRefGoogle Scholar
Taper, HS, Lemort, C & Roberfroid, MB (1998) Inhibition effect of dietary inulin and oligofructose on the growth of transplantable mouse tumor. Anticancer Res 18, 41234126.Google ScholarPubMed
Taper, HS & Roberfroid, M (1999) Influence of inulin and oligofructose on breast cancer and tumor growth. J Nutr 129, Suppl.1488S1491S.CrossRefGoogle ScholarPubMed
Taper, HS & Roberfroid, MB (2000) Inhibitory effect of dietary inulin or oligofructose on the development of cancer metastases. Anticancer Res 20, 42914294.Google ScholarPubMed
Van Loo, J (2004) The specificity of the interaction with intestinal fermentation by prebiotics determines their physiological efficacy. Nutr Res Rev 17, 8998.CrossRefGoogle ScholarPubMed
Van Loo, J & Jonkers, N (2001) Evaluation in human volunteers of the potential anticarcinogenic activities of novel nutritional concepts: prebiotics, probiotics and synbiotics (the SYNCAN project QLK1-1999-00346). Nutr Metab Cardiovasc Dis 11, 8793.Google ScholarPubMed
Verghese, M, Rao, DR, Chawan, CB, Williams, LL & Shackelford, LA (2002) Dietary inulin suppresses azoxymethane-induced aberrant crypt foci and colon tumors at the promotion stage in young Fisher 344 rats. J Nutr 132, 28092813.CrossRefGoogle ScholarPubMed
Verghese, M, Walker, LT, Shackelford, LA, Chawan, CB, Van Loo, J (2003) Inhibitory effects of non-digestible carbohydrates of different chain lengths on AOM induced aberrant crypt foci in Fisher 344 rats. In Proccedings of the Second Annual AACR International Conference. Frontiers in Cancer Prevention Research, Phoenix, AZR, 2630 October 2003. Poster B186 Abstr.Google Scholar