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Prebiotic fibres: a natural source of cancer prevention.

With more than 11 million people being diagnosed every year, cancer is a leading cause of death worldwide. According to the World Health Organization, however, this disease is largely preventable. For example, it is well known that a change in dietary behaviour can contribute to a reduced exposure to cancer risk. Scientists and researchers are already dealing with the identification of carcinogens and their decreased presence in our diets. Yet, by contrast, other substances could also be used as dietary supplements to benefit from their protective functions. One such candidate is the family of short-chain fructo-oligosaccharides, soluble dietary fibres that can be added to food to enhance and provide prebiotic activity.

Colorectal Cancer

According to the World Cancer Research Fund, only 5% of deaths by cancer are caused by hereditary, genetic factors, underlying the great impact of our environment and nutrition on the development of such pathologies. In the case of colorectal cancer, which presents the highest incidence when we consider both sexes, scientific evidence has pointed out that a high intake of cooked red meat is positively correlated with a high risk of colorectal cancer--whereas the consumption of fruit and vegetables, when associated with physical activity, can probably decrease this risk. Based on an epidemiological study of rural Africans consuming a high-fibre based diet, Burkitt first developed the "dietary fibre hypothesis" as a protective factor of colorectal cancer in 1969. However, other studies provided conflicting results--potentially related to the heterogeneity of the tested fibres and of the basal diet. It has also been suggested that a consumption of more than 30 g per day of fibre would be needed to afford protection against colorectal cancer. (1)

Prebiotic Fibres

Short-chain fructo-oligosaccharides (scFOS) are soluble fibres that are already used for food supplementation because of their nutritional and health benefits. They occur naturally in many vegetables, such as onions, garlic and wheat, but can also be produced from sucrose. The B1-2 link between the different molecules of glucose and fructose (Figure 1) is not hydrolysed by digestive enzymes and can only be fermented by certain strains of bifidobacteria and lactobacilli. Thus, scFOS belong to the family of prebiotic ingredients that are selectively fermented ingredients that allow specific changes in the composition and/or activity in the gastrointestinal microflora that confer well-being and health benefits to the host. (2) ScFOS are one of the most efficient prebiotic ingredients to stimulate the growth of bifidobacteria within the colon. Their bifidogenic effect starts at 2.5 g and proportionally increases according to the dose up to 10 g/day. (3) The modification of the colonic microflora with the consumption of scFOS leads to higher concentrations of short-chain fatty acids such as butyrate and maintains a slightly acidic pH in the lumen. By stimulating the growth and increasing the fermentative activities of bifidobacteria, scFOS have demonstrated their efficiency to beneficially improve the colonic environment and improve digestive comfort. (4) Furthermore, prebiotic ingredients are known to act at different levels to reduce the exposure of the colon to carcinogens and modulate cellular events that are important for cancer prevention.

[FIGURE 1 OMITTED]

[FIGURE 3 OMITTED]

Mechanism of Action:

The Butyrate Effect

Epithelial cells are normally renewed every 5 to 7 days. This is a process in which butyrate plays an important role by directly affecting the level of gene expression, which is involved at different steps of the cell cycle. Butyrate stimulates the proliferation of stem cells near the base of the crypt in the mucosa, and enhances the differentiation of the epithelial cells when they migrate up the crypt. (5) Any disturbance of this cycle may lead to aberrant epithelial cells, which are associated with the onset of carcinogenesis. (6,7)

The development of a cancerous tumour is initiated by a hyperproliferation of the intestinal mucosa cells at the level of the villi. Normally, cells should already be differentiated when they migrate from the crypt to the villi. This hyperproliferation of the cell mucosa leads to the development of an early adenoma, which further evolves into an advanced adenoma and carcinoma, which is able to trigger metastatic disease. According to in vitro experiments, butyrate seems to have a protective effect by inhibiting the hyperproliferation of cells along the villi and by inducing the apoptosis (programmed cell death) of the adenomic and carcinomic cells. (7)

Reduced Carcinogen Exposure

In addition to the beneficial impact of higher butyrate concentrations in the colon, scFOS can also affect carcinogenic exposure levels of the epithelial mucosa. In animals, scFOS have been shown to reduce the faecal concentration of polyamines (such as putrescine). (8) These polyamines can be provided by the diet or produced by bacterial fermentation occurring in the distal part of the colon, and have been recognized as potential carcinogens for the colon.

The bacterial metabolism of bile acids is of great importance when considering colorectal cancer. The bacterial degradation of primary bile acids leads to the accumulation of secondary bile acids (such as lithocholic acid) that have demonstrated capacities to induce cell necrosis or to promote tumour activity during in vitro studies with animal models. By maintaining slightly acidic pH conditions, scFOS consumption may limit the production of secondary bile acids and reduce colonic exposure to these toxic compounds.

Prevention of Tumours in Animals

The effect of scFOS to stimulate the production of butyrate has been clearly demonstrated in several animal studies investigating the effect of scFOS on colorectal carcinogenesis. A comparison of the capacity of different fibres to increase butyrate production confirmed that only fibres promoting stable butyrate production in the colon, such as scFOS, are likely to have an effect on the development of colorectal cancer in rats--by reducing the number of aberrant crypt foci, considered as precancerous lesions of the colonic epithelium. (9) Another study confirmed the effect of scFOS to reduce the number of colon tumours.

[FIGURE 2 OMITTED]

It was observed in Min mice (genetically predisposed to adenomatous polyposis and sporadic colon cancer) that were supplemented with scFOS instead of receiving either a wheat bran-enriched or control diet (Figure 2). (10) This effect seemed to be linked to the interaction between the digestive flora modified by scFOS and the intestinal immune system. Indeed, after receiving scFOS, the mice also showed an increased number of lymphoid nodules along their intestine.

In Humans

Patients with adenomatous polyps or colon cancer present a modified pattern of colonic fermentation, illustrated by lower butyrate concentrations than in healthy subjects. (11) The daily consumption of scFOS modifies the profile of the colonic microflora as well as its fermentative activities. In patients with small adenomas, the consumption of 10 g of scFOS per day can help to enhance the production of butyrate and increase its concentration until it reaches values observed in healthy patients. (12)

As mentioned above, a wide range of bacterial enzymatic activities is able to generate potentially carcinogenic metabolites. For example, B-glucuronidase is an important enzyme that releases toxic aglycones in the colon. In humans, probably as a result of an increased proportion of bifidobacteria and lactobacilli, scFOS have been shown to significantly reduce the activity of B-glucuronidase after 8 days of supplementation at 10 g per day, whereas high-risk diets for colorectal cancer have generally shown an increase of this activity compared with low-risk diets. (13)

Considering this effect, scFOS have also been shown to influence the metabolism of bile acids in the colon. Furthermore, epidemiological studies have highlighted elevated concentrations of secondary bile acids in populations at high risk of developing colorectal cancer. In humans, scFOS were shown to increase faecal concentrations of primary bile acids while decreasing the concentration of secondary bile acids (Figure 3). (12)

Through their effect on the gastrointestinal flora, short-chain fructo-oligosaccharides can beneficially alter bacterial metabolism by increasing the population of bifidobacteria and enhancing the production of butyrate in people with a low bifidobacteria count or insufficient butyrate production. They can also reduce the exposure of the colon to carcinogens. Thus, short-chain fructooligosaccharides can stand as candidate fibres to be tested in prevention studies for colorectal cancer or as a nutritional supplement for patients receiving chemicalbased treatments.

References

(1.) L.R. Fergusson and P.J. Harris, "The Dietary Fibre Debate: More Food for Thought--Commentary," Lancet 361, 1487-1488 ( 2003).

(2.) G.R. Gibson, et al., "Dietary Modulation of the Human Colonic Microbiota: Updating the Concept of Prebiotics," Nutrition Research Reviews 17(2), 259-275 (2004).

(3.) Y. Bouhnik, et al., "The Capacity of Short-Chain Fructo-Oligosaccharides to Stimulate Fecal Bifidobacteria: A Dose-Response Relationship Study in Healthy Humans," Nutrition Journal 5(8), Published Online (2006).

(4.) D. Desvignes, et al., "Regular Consumption of Short-Chain Fructo-Oligosaccharides Improves Digestive Comfort of Subjects with Minor Digestive Disorders (FDD)," NAFAS 3(6), 57-58 (2005).

(5.) J.G. Smith, W.H. Yokoyama and J.B. German, "Butyric Acid from the Diet: Actions at the Level of Gene Expression," Critical Reviews in Food Science and Nutrition 38(4), 259-297 (1998).

(6.) S. Salminen, et al., "Functional Food Science and Gastrointestinal Physiology and Function," British Journal of Nutrition 80, S147-S171 (1998).

(7.) W. Scheppach, H. Luehrs and T. Menzel, "Beneficial Health Effects of Low-Digestible Carbohydrate Consumption," British Journal of Nutrition 85(Suppl 1), S23-S30 (2001).

(8.) H. Hussein and G. Sunvold, "Dietary Strategies to Decrease Dog and Cat Fecal Odor Components," in G. Reinhart and D. Carey, Eds, Recent Advances in Canine and Feline Nutrition (Orange Frazer Press, Wilmington, Ohio, USA, 2000) pp 153-168.

(9.) P. Perrin, et al., "Only Fibers Promoting a Stable Butyrate Producing Colonic Ecosystem Decrease the Rate of Aberrrant Crypt Foci in Rats," Gut 48, 53-61 (2001).

(10.) F. Pierre, et al., "Short-Chain Fructoligosaccharides Reduce the Occurence of Colon Tumors and Develop Gut-Associated Lymphoid Tissue in Min Mice," Cancer Research 57, 225-228 (1997).

(11.) G.A. Weaver, et al., "Short Chain Fatty Acid Distribution of Enema Samples from a Sigmoidoscopy Population: An Association of High Acetate and Low Butyrate Ratios with Adenomatous Polyps and Colon Cancer," Gut 29, 1539-1543 (1988).

(12.) M.C. Boutron-Ruault, et al., "Effects of a 3-Month Consumption of Short-Chain Fructo-Oligosaccharides on Parameters of Colorectal Carcinogenesis in Patients with or without Small Large Colorectal Adenomas," Nutrition and Cancer 53(2), 160-168 (2005).

(13.) J. Rafter, et al., "PASSCLAIM: Diet-Related Cancer," European Journal of Nutrition 43(2), ii47-ii84 (2004).

For more information

Frederique Respondek

Beghin Meiji

Z.I. et Portuaire BP 32, F-67390 Marckolsheim, France.

Tel. +33 3 8858 6086

www.beghin-meiji.com
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Title Annotation:prebiotic fibres
Author:Respondek, Frederique
Publication:Nutraceutical Business & Technology
Geographic Code:1USA
Date:Jan 1, 2007
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