Fructooligosaccharides are widely used as a health food ingredient with a new concept of “prebiotics” in many countries. So far, many extensive studies on these unique oligosaccharides have been made since the author found the usefulness of fructooligosaccharides as a bifidus-promoting factor 20 years ago. Japan is considered the most-developed country concerning the application of and studies on functional foods. The studies on fructooligosaccharides have played the role of an engine for the development of functional foods and have been accompanied with the widespread use of Foods for Specified Health Use in Japan. The International Symposium on Fructooligosaccharides was held at Keidanren Kaikan in Tokyo on July 3, 2001. The object of this meeting was to review and to summarize the updated scientific findings on fructooligosaccharides and related matters. Ten speakers, including overseas scientists, were invited to present lectures on topics related to fructooligosaccharides from various aspects. They were aided by two cochairpersons, Professor Hidemasa Hidaka, Tokiwa Junior College, and Professor Takashi Sakata, Ishinomaki Senshu University. The symposium was sponsored by Meiji Seika Kaisha, Ltd., Tokyo. A total of 450 participants attended. This issue of Bioscience and Microflora provides all papers presented at the symposium. I believe this proceeding will be valuable to those who are interested in the functions and health benefits of prebiotics and intestinal microflora.
During the past 5 decades, research in intestinal flora has made rapid progress, which includes the following: (1) development of a comprehensive culture method; (2) establishment of the classification and identification of intestinal anaerobic bacteria; (3) accumulation of microecological evidence and the beneficial and harmful functions of intestinal flora in human health. Thus it is of great importance to promote beneficial bacteria such as bifidobacteria and to suppress harmful bacteria such as clostridia among the intestinal flora. These advances in intestinal flora research are the background for the appearance of functional foods, which are classified into 3 groups based on their mechanisms of action: probiotics, prebiotics, and biogenics. Prebiotics are nondigestible food ingredients, which beneficially affect the host by selectively stimulating the growth of beneficial bacteria in the colon and/or by suppressing the growth of harmful bacteria there. The prebiotics have the potential to improve host health: The candidates are nondigestible oligosaccharides such as lactulose, stachyose, raffinose, fructo-oligosaccharides, soybean oligosaccharides, lactosucrose, galactooligosaccharides, isomalto-oligosaccharides, xylo-oligosaccharides, and palatinose. Most oligosaccharides are fermented in vitro by Bifidobacterium species (though not by B. bifidum) and to a limited degree by the Bacteroides fragilis group and Enterococcus, but they are not fermented by C. perfringens or Escherichia coli. The oral administration of oligosaccharides enhances the proliferation of intestinal bifidobacteria, improving the properties of the host's stool and scavenging the intestine, thereby altering host lipid metabolism in a beneficial way.
Previous reports have demonstrated through the use of animal models that dietary fructooligosaccharides (FOS) exert stimulatory effects on the absorption of the minerals; calcium, magnesium, and iron. Recently, these effects were also clinically confirmed in humans. This paper reviews studies that used the techniques of molecular biology to elucidate the mechanisms by which FOS stimulates calcium absorption for which the small intestine has long been considered a primary site. However, Ohta et al. reported that the large intestine, and the cecum in particular, has an important role.This conclusion was based on the observation that the stimulatory effect of FOS on calcium absorption was not observed in cecectomized rats. The contribution of paracellular and transcellular paths was suggested for the stimulation caused by FOS. Transcellular transport is a multistep process comprising several components and is under the regulation of vitamin D. One component is calbindin-D9k (CaBP), a calcium binding protein. The upstream region of the CaBP gene was analyzed, and a responsive sequence for vitamin D receptor was identified. Mucosal cells were then obtained from FOS-fed rats, and the expression of CaBP protein and mRNA were determined. Dietary FOS decreased the expression of CaBP in the small intestine, but resulted in increased levels in the cecum and colorectum. Since protein and mRNA both demonstrated similar patterns of expression, the effects of FOS can be seen to affect CaBP at the transcription level. Furthermore, the changes in CaBP expression were proportional to both the level of apparent calcium absorption and the amount of FOS ingested. This means that the increase of calcium absorption induced by FOS comprises paracellular and CaBP-mediated transcellular transport. In a hypothetical model, short-chain organic acids produced from FOS by fermentation were proposed as key elements to regulate both the paracellular and the transcellular transport of calcium. However, the molecular mechanisms of this regulation have not yet been clarified.
Several studies have been carried out to establish the role of calcium and magnesium in bone. These minerals may play an important role in bone structure or strength. Fructooligosaccharides (FOS) are known to be stimulators of intestinal mineral absorption. In intact rats, bone volume and the mineral content (Ca, and Mg) of the bone surface are greater in FOS-fed rats. Moreover, a significant relationship exists between the absorption of these minerals and their content in bone. Osteopenia is known to follow total gastrectomy in animals, leading to the severe concordant loss of both cortical and cancellous bone. These findings are similar to senile osteoporosis in humans. Dietary FOS completely prevents the gastrectomy-induced osteopenia in rats. If similar effects are found in humans, an increase in mineral deposition in bone during growth may contribute to the prevention of bone disease with age. Thus FOS might be a promising prebiotic for bone.
This paper briefly reviews the general process through which GTC Nutrition Company was able to demonstrate through scientific procedures the safety and naturalness of short-chain fructooligosaccharides (scFOS ®) to the U.S. Food and Drug Administration (FDA). The result of the successful regulatory petition was an FDA “generally recognized as safe (GRAS) ” status of fructooligosaccharides as a food ingredient and consequently a broader market recognition and acceptance of our short-chain fructooligosaccharides as a functional food ingredient.
The outstanding of fructooligosaccharide as a nondigestible dietary fiber has been proved for the prevention of hypercholesterolemia, overgrowth of pathogen bacteria, colon cancer, and enhancement of mucosal immune response.The primary function of beneficial intestinal microflora is to protect the intestinal tract from the proliferation of infection or harmful bacteria. Bifidobacterium bifidum produces volatile fatty acids, which provide important metabolic energy, and acidifies the bowel, which inhibits the growth of harmful bacteria, including Salmonella, Shigella, Clostridium, Campilobacter jejuni, and Escherichia coli. When the population of beneficial microflora decreases the gastrointestinal environment makes a subtle chemical shift, which allows harmful bacteria such as Clostridium perfringens and E. coli to proliferate. One clinical manifestation of this imbalance is diarrhea. In developing countries, diarrhea is still the most important cause of child morbidity and mortality with an estimation of 1.3 billion episodes each year in children under 5 years old. FOS acts like an efficient intestinal “fertilizer” by feeding beneficial intestinal microflora and helping them to reproduce. The improvement in the intestinal microflora was followed by a relief of constipation, or loose stool;decreased formation of putrefactive products in the large intestine, improved serum lipids in hyperlipidemia; and reduced total cholesterol, triglycerides, blood glucose, and blood pressure. Studies show that the duration of diarrhea in children who ingested FOS were shorter than in those who ingested a placebos (2.62 days versus 4.24 days). The pH of stool in children who ingested FOS was significantly lower than in children who did not.
Short-chain fatty acids are products of nondigestible oligo- and poly-saccharides fermented by vast numbers of colonic microorganisms called microbial flora. Produced in the colon they are readily absorbed and are metabolized in the liver and muscle tissues providing energy to the human body. The colonic mucosal cells consume butyric acid, a kind of short-chain fatty acid, as a main and indispensable energy source. A deficiency in butyric acid leads to a malfunction of the colon. This means that nondigestible sugars, including prebiotics, are essential for human health. Short-chain fatty acids are not merely sources of energy; they provide beneficial physiological actions. These include improving the absorption of water and several minerals, especially calcium, magnesium, and iron, and suppressing the synthesis of liver cholesterol. Butyric acid is marked as a suppressor of colon cancer, a lifestyle-related disease. This fermentation product reduces cell proliferation and induces apoptosis in the mutated cells. Butyric acid is very likely to be effective for the prevention of this fatal disease. How do short-chain fatty acids work in various cells? This has not been revealed.The research into short-chain fatty acids may clarify the physiological implications of the colonic fermentation and prebiotics.
Fructooligosaccharides are an ideal source of fermentable fiber for medical foods. Typically, medical foods are liquid, many of which are fed to patients through a tube. Liquid medical foods that are fed through a tube must be low in viscosity. Fructooligosaccharides are soluble and will not clog feeding tubes and do not significantly increase the viscosity of the product. Rationale for the use of fructooligosaccharides in medical foods includes: normalization of bowel function, maintenance of large bowel integrity, restoration of colonization resistance, alteration in route of nitrogen excretion, and improvement in calcium absorption. Normalization of bowel function refers to the treatment or prevention of constipation or diarrhea in patients receiving a medical food. Fructooligosaccharides, through anaerobic fermentation by colonic bacteria and the production of short chain fatty acids, may be useful in preventing large bowel atrophy or treating distal ulcerative colitis. Fructooligosaccharides, by selectively supporting the growth of bifidobacteria or producing an environment in the colon (e.g., increased short chain fatty acid concentration or decreased pH) that is not conducive to the growth of certain pathogenic organisms, may help restore colonization resistance. Anaerobic fermentation of fructooligosaccharides, leading to the bacterial cell growth and a reduction is colonic pH, may shift nitrogen excretion from the urinary to the fecal route. Improvements in calcium absorption may occur through mechanisms involving short chain fatty acid absorption and a reduction in large bowel pH. Overall, compatibility with liquid products and numerous physiological benefits to the patient justify the use of fructooligosaccharides in medical foods.
Short-chain fructooligosaccharides occur in a number of edible plants, such as chicory, onions, asparagus, wheat. They are produced industrially from sucrose. They are a group of linear fructose oligomers with a degree of polymerisation ranging from 1 up to 5 (oligosaccharides). Short-chain fructooligosaccharides to a large extent escape digestion in the human upper intestine and reach the colon where they are totally fermented mostly to lactate, short chain fatty acids (acetate, propionate and butyrate), and gas. Butyrate is the most interesting of the short chain fatty acids (SCFA) since, it regulates cell growth and differentiation of colonocyte. In addition to this trophic effect, butyrate stimulates the immunogenicity of the cancerous cells. Short-chain fructooligosaccharides also stimulate bifidobacterial growth. The colonic microflora has a considerable influence on the immune system of the host. The intestinal mucosa, play an important role in the immune system too, it is the largest immunological organ of the body containing. The gutassociated lymphoid tissue (GALT) plays a key role according to its singular interface situation in the body and constitutes an important line of defence which is confronted with a large range of antigenic or immunomodulating substances.Recent founding in animal models clearly demonstrate that pre and probiotic may exert beneficial effects on gut health by enhancing GALT responses directly or indirectly by the mediation of butyrate and lactic bacteria. GALT may play a pivotal role in the rejection of nascent colon tumours. Intestinal microflora modulates the GALT responses and recent founding in animal models clearly demonstrate that pre and probiotic may exert beneficial effects on gut health by enhancing GALT responses directly or indirectly by the mediation of butyrate. The demonstration of the potential health benefits of sc-FOS on reduction risk of colon cancer is an active field of research in human nutrition. The sc-FOS, in animal models, reduce colon tumour development by enhancing both colon butyrate concentrations and local immune system effectors. The objective of this review is to discuss the critical role of GALT and its effectors, associated to butyrate, on colorectal cancer prevention. Both target functions have shown to be enhanced by sc-FOS.
The intestinal immune system is an extremely elaborate biological defense system. It has characteristic immunological organs and cells for protecting against pathogenic bacteria and the suppression of the onset of food allergy.Immunoglobulin A is generated to prevent the invasion of pathogenic bacteria, and oral tolerance is induced to inhibit food allergy. Intestinal bacteria strongly influence the activation and modulation of the intestinal immune system.Moreover, prebiotics contribute to the stimulation of specific bacteria in the large intestine. Raffinose, a typical prebiotic, is found to inhibit the production of immunoglobulin E, which is associated with the onset of allergy.
[Background] Food allergies cause damage not only to the intestines of patients but to their livers as well, making it all the more important to discover what drugs are effective in preventing that damage. Accordingly, we studied the effectiveness of Chinese traditional medicine and FOS in helping to prevent damage caused by food allergies. [Methods] (1) 13C-methacetine was used to study the relationship between liver damage and cases of food allergy presentation.(2) Chinese traditional medicine (Hochu-Ekito = TJ-41) was administered orally to mice twice a day for 2 weeks in a drug study of the food allergy model.(3) The effect of FOS on fecal organic acid production was observed in a study of FOS-treated mice. [Results] (1) As a result of the 13CO2 excretion pattern, the relationship between liver function and food allergies was confirmed.(2) The serum ALT levels decreased in mice treated with TJ-41.(3) Short-chain fatty acids such as butyrate were significantly higher in the FOS-treated group than in the control group. [Conclusion] Damage not only to the intestines but also the liver of food allergy patients was confirmed. TJ-41 and FOS were found to prevent this allergy-related damage, showing that FOS is very useful for allergic patients.