Dietary synbiotics reduce cancer risk factors in polypectomized and colon cancer patients.

BACKGROUND: Animal studies suggest that prebiotics and probiotics exert protective effects against tumor development in the colon, but human data supporting this suggestion are weak. OBJECTIVE: The objective was to verify whether the prebiotic concept (selective interaction with colonic flora of nondigested carbohydrates) as induced by a synbiotic preparation-oligofructose-enriched inulin (SYN1) + Lactobacillus rhamnosus GG (LGG) and Bifidobacterium lactis Bb12 (BB12)-is able to reduce the risk of colon cancer in humans. DESIGN: The 12-wk randomized, double-blind, placebo-controlled trial of a synbiotic food composed of the prebiotic SYN1 and probiotics LGG and BB12 was conducted in 37 colon cancer patients and 43 polypectomized patients. Fecal and blood samples were obtained before, during, and after the intervention, and colorectal biopsy samples were obtained before and after the intervention. The effect of synbiotic consumption on a battery of intermediate bio-markers for colon cancer was examined. RESULTS: Synbiotic intervention resulted in significant changes in fecal flora: Bifidobacterium and Lactobacillus increased and Clostridium perfringens decreased. The intervention significantly reduced colorectal proliferation and the capacity of fecal water to induce necrosis in colonic cells and improve epithelial barrier function in polypectomized patients. Genotoxicity assays of colonic biopsy samples indicated a decreased exposure to genotoxins in polypectomized patients at the end of the intervention period. Synbiotic consumption prevented an increased secretion of interleukin 2 by peripheral blood mononuclear cells in the polypectomized patients and increased the production of interferon gamma in the cancer patients. CONCLUSIONS: Several colorectal cancer biomarkers can be altered favorably by synbiotic intervention.

Probiotic and prebiotic influence beyond the intestinal tract.

Probiotics and prebiotics have long been appreciated for their positive influences on gut health. Research on the mechanisms and effects of these agents shows that their impact reaches beyond the intestine. Effects on the microecology and pathology of the oral cavity, stomach, and vaginal tract have been observed. Likely mediated through immune influences, systemic effects such as reduced severity of colds or other respiratory conditions, impact on allergy incidence and symptoms, and reduced absences from work or daycare have also been noted. These observations, among others, suggest a broader spectrum of influence than commonly considered for these unique substances.

The specificity of the interaction with intestinal bacterial fermentation by prebiotics determines their physiological efficacy.

The concept of prebiotic food ingredients is an important recent development in nutrition. The concept has attracted a great deal of attention, and many food ingredients (mainly dietary carbohydrates) have been claimed to be 'prebiotic'. It is emphasised that in order to be called prebiotic, a compound should be: (1) non-digestible; (2) fermentable; (3) fermentable in a selective way. These properties should be demonstrated in human volunteers in at least two independent dietary intervention trials. On the basis of published and unpublished results, it is shown in the present paper that the way in which a prebiotic influences intestinal fermentation is the key to its physiological properties. This statement is illustrated mainly by considering an established group of prebiotics, the beta(2-1) fructans. These linear molecules show a strong discontinuity in physicochemical properties as the chains become longer. The beta(2-1) fructans with a chain length of up to ten monomer units are very soluble and are particularly 'bifidogenic'. Longer chains (ten to sixty-five monomer units) are poorly soluble in water, they have less pronounced bifidogenic properties, and they are fermented more slowly. It was observed that a combination of short-chain and long-chain fructans (Synergy 1) is physiologically (for example, increasing mineral absorption, suppressing carcinogenesis, modulating lipid metabolism, etc) more active than the individual fractions. A possible mechanism is described in the present review. From an in-depth overview of the literature it is confirmed that for prebiotic action, the 'selectivity principle' for intestinal fermentation is determinative for the type and for the efficiency of physiological activity. It is confirmed that prebiotics act through their influence on intestinal fermentation.

Fermentable carbohydrate alters hypothalamic neuronal activity and protects against the obesogenic environment.

Obesity has become a major global health problem. Recently, attention has focused on the benefits of fermentable carbohydrates on modulating metabolism. Here, we take a system approach to investigate the physiological effects of supplementation with oligofructose-enriched inulin (In). We hypothesize that supplementation with this fermentable carbohydrate will not only lead to changes in body weight and composition, but also to modulation in neuronal activation in the hypothalamus. Male C57BL/6 mice were maintained on a normal chow diet (control) or a high fat (HF) diet supplemented with either oligofructose-enriched In or corn starch (Cs) for 9 weeks. Compared to HF+Cs diet, In supplementation led to significant reduction in average daily weight gain (mean ± s.e.m.: 0.19 ± 0.01 g vs. 0.26 ± 0.02 g, P < 0.01), total body adiposity (24.9 ± 1.2% vs. 30.7 ± 1.4%, P < 0.01), and lowered liver fat content (11.7 ± 1.7% vs. 23.8 ± 3.4%, P < 0.01). Significant changes were also observed in fecal bacterial distribution, with increases in both Bifidobacteria and Lactobacillius and a significant increase in short chain fatty acids (SCFA). Using manganese-enhanced MRI (MEMRI), we observed a significant increase in neuronal activation within the arcuate nucleus (ARC) of animals that received In supplementation compared to those fed HF+Cs diet. In conclusion, we have demonstrated for the first time, in the same animal, a wide range of beneficial metabolic effects following supplementation of a HF diet with oligofructose-enriched In, as well as significant changes in hypothalamic neuronal activity.

How chicory fructans contribute to zootechnical performance and well-being in livestock and companion animals.

Animalia typically have a digestive tract for digestion of food and absorption of water. The intestinal tract is a nutrient-rich environment, as the digestive system of the host often lacks enzymes necessary to degrade certain food components. Other sources of nutrients originate from the high turnover of epithelial cells covering the intestinal surface and from the production of mucus. As the lining of the intestine is continuous with the skin, the interior intestinal space (chyme) of the intestine is external environment. There, as a consequence, is a continuous contamination pressure by bacteria that during evolution proved to be useful for further metabolism of nutrients, which the host failed to utilize. Intestinal flora coevolved with its host and the selection was driven by the intestinal architecture (morphology and transit scheme) and dietary habits of the host. Different animal species have different typical profiles of intestinal bacterial populations. The pertinently existing inter-individual differences between members of certain species are a variation on this typical profile. Animals in general seem not to be able to hydrolyze beta-glycoside bonds, such as the chicory inulin beta(2-1) bond. Chicory fructans were shown to be prebiotic (selectively interacting with intestinal bacterial ecosystem) (1) in humans and in animals, including livestock and pets. This article describes how prebiotic feeding contributes to zootechnical performance of livestock (pig, calf, horse, broiler, laying hen, and fish), which is driven by intestinal functioning, and to animal well-being (mainly pets but also livestock,) which has intestinal but also derived systemic origins.

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

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.

Markers to measure immunomodulation in human nutrition intervention studies.

Normal functioning of the immune system is crucial to the health of man, and diet is one of the major exogenous factors modulating individual immunocompetence. Recently, nutrition research has focused on the role of foods or specific food components in enhancing immune system responsiveness to challenges and thereby improving health and reducing disease risks. Assessing diet-induced changes of immune function, however, requires a thorough methodological approach targeting a large spectrum of immune system parameters. Currently, no single marker is available to predict the outcome of a dietary intervention on the resistance to infection or to other immune system-related diseases. The present review summarises the immune function assays commonly used as markers in human intervention studies and evaluates their biological relevance (e.g. known correlation with clinically relevant endpoints), sensitivity (e.g. within- and between-subject variation), and practical feasibility. Based on these criteria markers were classified into three categories with high, medium or low suitability. Vaccine-specific serum antibody production, delayed-type hypersensitivity response, vaccine-specific or total secretory IgA in saliva and the response to attenuated pathogens, were classified as markers with high suitability. Markers with medium suitability include natural killer cell cytotoxicity, oxidative burst of phagocytes, lymphocyte proliferation and the cytokine pattern produced by activated immune cells. Since no single marker allows conclusions to be drawn about the modulation of the whole immune system, except for the clinical outcome of infection itself, combining markers with high and medium suitability is currently the best approach to measure immunomodulation in human nutrition intervention studies. It would be valuable to include several immune markers in addition to clinical outcome in future clinical trials in this area, as there is too little evidence that correlates markers with global health improvement.

Prebiotics promote good health: the basis, the potential, and the emerging evidence.

BACKGROUND: The prebiotics concept, which was launched in 1995, concerns nondigested and selectively fermented carbohydrate food ingredients. It was thought that their effect in the colon could reduce risk for disease. The prebiotic concept is revisited and possible mechanisms are proposed. The physiologic consequences of prebiotic consumption are evaluated in terms of potential to reduce risk for disease. This is a compilation of several research papers, each of which complied with the World Medical Association Declaration of Helsinki. METHODS: For human dietary intervention trials, the aim was to perform double-blind, placebo-controlled, cross-over studies. A parallel design was used only for long-term studies. Most research has been done with beta(2-1) fructans, so they are used as an example of prebiotics here. RESULTS: The results are relevant to the fields of gut function, lipid metabolism, mineral absorption, bone formation, immunology, and cancer. CONCLUSION: It is observed that modification of intestinal flora by inherently selectively fermented prebiotics is central in determining their nutritional properties. They interact positively through the large intestinal surface with various physiologic processes and are thought to improve health status by reducing risk for disease (markers).

Nutritional responses to the presence of inulin and oligofructose in the diets of domesticated animals: a review.

Inulin and oligofructose are prebiotic oligosaccharides fermented in the large intestine. This article provides an extensive review of the effects of these oligosaccharides on gastrointestinal characteristics (microflora, pathogen control, epithelial cell proliferation, putrefactive compound production, fecal characteristics, and nutrient digestibility) and systemic metabolism of carbohydrates, nitrogen, lipids, and minerals in dogs, cats, horses, calves, pigs, poultry, and rabbits. In addition, intake of inulin and oligofructose and considerations in their supplementation to animal diets are discussed. Growth performance and meat production in livestock in response to inulin and oligofructose supplementation are addressed. Finally, the possible substitution of antibiotics with fructans in animal diets and directions for future research are presented.

PASSCLAIM--diet-related cancer.

BACKGROUND: The role of dietary factors in the aetiology of human cancer is an area, which has attracted intense interest in recent years. The suggestion that approximately one third of all cancers may be caused by an 'inappropriate' balance of food components has led to the attractive contention that we can significantly decrease cancer incidence through dietary recommendations and a change in dietary habits in populations. Thus, a key issue must be to establish clear criteria, which must be met in order to be able to make 'cancer risk reduction' claims for food components. In this area, the one true marker is the malignant human tumour, which for practical reasons is usually not accessible to claims. In its absence, we must rely on alternative markers--biomarkers/surrogate endpoints. This paper mainly deals with the link of these biomarkers to the endpoint tumour and their usefulness for making claims. Some claims have been made based on epidemiological studies. AIM: Can we identify targets/ biomarkers in the chain of events from initial 'exposure' to overt malignant tumour, whose modification can be used to make 'anticancer' claims for food components? RESULTS: We identified 18 targets/markers in the above chain of events whose modification 'have the potential' to be used for 'reduction of cancer risk' claims for food components. These targets/markers fall under 5 broad headings: tumours and preneoplastic changes; cellular targets/markers; gut luminal markers; angiogenesis and metastasis; carcinogen metabolising enzymes; genetic events. CONCLUSIONS: The strongest markers presently available are precancerous lesions (e. g. polyps or aberrant crypt foci) in humans and precancerous lesions and tumours in animal models. The only marker that presently can be used for a 'reduction of disease risk' claim (type B) for food components is 'polyp recurrence'. Type B claims cannot be made on the basis of results in animal models. All of the other biomarkers examined presently lack validation against the 'true endpoint', the tumour, and thus cannot be used for type B claims. 'Reduction of disease risk' claims in the area of 'diet-related cancer' should be based primarily on human intervention studies using relevant/acceptable endpoints. An important area for future research will be the validation of these surrogate endpoints.