Prebiotic effects: metabolic and health benefits

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

What is beneficial for health? The concept of functional food.

'Functional Food' is now a very popular term. The conceptual approach developed in the EU-founded FUFOSE (Functional Food Science in Europe) project is rather restrictive, making functional food a food product to be part of the usual dietary pattern. Functional food science that supports the development of functional foods is and must remain part of the science of nutrition. Finally, all that exercise, that extended over the last 3 years, was function-driven because the functions and their modulation are universal, as opposed to a food or food component-driven approach,which is likely to be very much influenced by local, traditional or cultural characteristics

Metabolic activation of drugs in mutagenicity tests in vitro.

The metabolic pathways of chemical compounds of pharmaceutical interest are reviewed in relation to the role of activation and detoxification in the process of mutagenicity. The properties and subcellular localization of the enzymes involved are given together with the main reactions they catalyze. The role of metabolism in mutagenicity testing in vitro is discussed with special emphasis on the choice of the enzymatic system. Parameters such as species, strain, sex, diet, and induction are considered. The effect of various enzymatic effectors added in vitro is also discussed. It is concluded that the metabolism of drugs is very complex, involving both activation and detoxification processes catalyzed by a large variety of enzymes. Production of mutations in vitro in prokaryotic or eukaryotic cells is the results of a balance between all those pathways. Metabolic activation thus merits special attention

Functional foods: concepts and application to inulin and oligofructose.

A food can be regarded as functional if it is satisfactorily demonstrated to affect beneficially one or more target functions in the body, beyond adequate nutritional effects, in a way which is relevant to either the state of well-being and health or the reduction of the risk of a disease. Health claims are expected to be authorized for functional foods based either on enhanced function (type A claim) or disease risk reduction (type B claim). Their development is a unique opportunity to contribute to the improvement of the quality of the food offered to consumer's choice for the benefit of his well-being and health. But only a rigorous scientific approach producing sound data will guarantee its success. The functional food components that are discussed in the proceedings of the 3rd ORAFTI Research Conference are the inulin-type fructans, natural food components found in miscellaneous edible plants. They are non-digestible oligosaccharides that are classified as dietary fiber. The targets for their functional effects are the colonic microflora that use them as selective 'fertilizers'; the gastrointestinal physiology; the immune functions; the bioavailability of minerals; and the metabolism of lipids. Potential health benefits may also concern reduction of the risk of some diseases like intestinal infections, constipation, non-insulin dependent diabetes, obesity, osteoporosis or colon cancer. The present proceedings review the scientific data available and, by reference to the concepts in functional food science, they assess the scientific evidence which will be used to substantiate health claims

Functional food concept and its application to prebiotics.

A food can be regarded as functional if it is satisfactorily demonstrated to affect beneficially one or more target functions in the body, beyond adequate nutritional effects, in a way which is relevant to either the state of wellbeing and health or the reduction of the risk of a disease. A food can be made functional by increasing the concentration, adding or improving the bioavailability of a particular component. Functional food science will serve to establish claims based either on enhanced function or disease risk reduction. Inulin and oligofructose are functional food ingredients present in miscellaneous edible plants. They are non-digestible oligosaccharides classified as dietary fibres. The target for their functional effects is the colonic microflora that ferment them and for which they serve as selective "fertilizers"; the gastrointestinal physiology; the immune functions; the bioavailability of minerals; the metabolism of lipids; and colonic carcinogenesis. The scientific data available on the nutritional effects of inulin and oligofructose provide strong evidence for a prebiotic effect (i.e., selective stimulation of growth of bifidobacteria in colonic microbiota), improvement of bowel habit (both stool frequency and stool weight) and improved calcium bioavailability

Introducing inulin-type fructans.

Inulin is a generic term to cover all beta(2-->1) linear fructans. Chicory inulin is a linear beta(2-->1) fructan (degree of polymerisation (DP) 2 to 60; DPav=12), its partial enzymatic hydrolysis product is oligofructose (DP 2 to 8; DPav=4), and by applying specific separation technologies a long-chain inulin known as inulin HP (DP 10 to 60; DPav=25) can be produced. Finally, a specific product known as oligofructose-enriched inulin is obtained by combining chicory long-chain inulin and oligofructose. Because of the beta-configuration of the anomeric C2 in their fructose monomers, inulin-type fructans resist hydrolysis by intestinal digestive enzymes, they classify as 'non-digestible' carbohydrates, and they are dietary fibres. By increasing faecal biomass and water content of the stools, they improve bowel habits, but they have characteristic features different from other fibres. They affect gastrointestinal functions not because of their physico-chemical properties but rather because of their biochemical and physiological attributes. In the colon, they are rapidly fermented to produce SCFA that are good candidates to explain some of the systemic effects of inulin-type fructans. Fermentation of inulin-type fructans in the large bowel is a selective process; bifidobacteria (and possibly a few other genera) are preferentially stimulated to grow, thus causing significant changes in the composition of the gut microflora by increasing the number of potentially health-promoting bacteria and reducing the number of potentially harmful species. Both oligofructose and inulin are prebiotic. They also induce changes in colonic epithelium stimulating proliferation in the crypts, increasing the concentration of polyamines, changing the profile of mucins, and modulating endocrine as well as immune functions. From a nutrition labelling perspective, inulin-type fructans are not only prebiotic dietary fibres; they are also low-calorie carbohydrates [6.3 kJ/g (1.5 kcal/g)]. Supported by the results of a large number of animal studies and human nutrition intervention trials, the claim 'inulin-type fructans enhance calcium and magnesium absorption' is scientifically substantiated, but different inulin-type fructans have probably a different efficacy (in terms of effective daily dose), the most active product being the oligofructose-enriched inulin. A series of animal studies demonstrate that inulin-type fructans affect the metabolism of lipids primarily by decreasing triglyceridaemia because of a reduction in the number of plasma VLDL particles. The human data largely confirm the animal experiments. They demonstrate mainly a reduction in triglyceridaemia and only a relatively slight decrease in cholesterolaemia mostly in (slightly) hypertriglyceridaemic conditions. Inulin appears thus eligible for an enhanced function claim related to normalization of blood triacylglycerols. A large number of animal data convincingly show that inulin-type fructans reduce the risk of colon carcinogenesis and nutrition intervention trials are now performed to test that hypothesis in human subjects known to be at risk for polyps and cancer development in the large bowel

Dietary modulation of experimental neoplastic development: role of fat and fiber content and calorie intake.

Cancer is still one of the major causes of death in the industrialized countries but locally prevailing lifestyles may dictate the kinds of cancer seen among populations of different geographical areas. Dietary habits and, in particular, the nature and/or the amount of fat, calorie and/or vegetable fiber which are consumed in these countries are among the most frequently quoted etiological factors which may account for this situation. Epidemiological and experimental evidence has accumulated which, even though it can be used to support these conclusions, is still a matter of considerable debate. Modulation of neoplastic development is a concept which has been elaborated to overcome the fact that many experimental observations are not really taken into consideration by the classical 2-step theory of carcinogenesis. It is defined as the effect of any treatment which given before, during or after the initiation of a full carcinogenic process modifies the pattern of neoplastic development as evaluated by the kinetics of appearance, the incidence and/or the yield of histologically characterized malignant tumors. It is said to be positive or negative depending on whether it accelerates or slows down the process and increases or decreases the yield of malignant tumors respectively. From a review of the available experimental data, it is concluded that fat per se has, most probably, no modulating effect but that unbalanced diets rich in lipids could act as a positive modulator of chemically induced carcinogenesis by virtue of their capacity to cause a break in metabolic and proliferative homeostasis; that vegetable fibers as well as restriction in calorie intake could act as negative modulators of the same process because they could restore or help restore this homeostasis. It is thus proposed that to maintain dietary balance either by increasing fiber and/or by reducing total calorie intake is the most effective way to negatively modulate chemically induced carcinogenesis in experimental animals. To make the same recommendation to humans could most probably help preventing major cancers like breast and colon cancers