Prebiotics: future trends in health care Rupali Singh ...

28 downloads 0 Views 380KB Size Report
Dietary Supplement Health and Education Act of. 1994. Available at: http://vm.cfsan.fda.gov/dietsupp.html. 19. DeFelice SL (2002) FIM Rationale and Proposed ...
Prebiotics: future trends in health care

Rupali Singh, Pramod Kumar Sharma & Rishabha Malviya

Mediterranean Journal of Nutrition and Metabolism Official Journal of the Italian Association for Dietetics and Clinical Nutrition (ADI) a member of the Italian Federation of Nutritional Societies (FeSIN) ISSN 1973-798X Mediterr J Nutr Metab DOI 10.1007/ s12349-011-0065-8

1 23

Your article is protected by copyright and all rights are held exclusively by SpringerVerlag. This e-offprint is for personal use only and shall not be self-archived in electronic repositories. If you wish to self-archive your work, please use the accepted author’s version for posting to your own website or your institution’s repository. You may further deposit the accepted author’s version on a funder’s repository at a funder’s request, provided it is not made publicly available until 12 months after publication.

1 23

Author's personal copy Mediterr J Nutr Metab DOI 10.1007/s12349-011-0065-8

REVIEW

Prebiotics: future trends in health care Rupali Singh • Pramod Kumar Sharma Rishabha Malviya



Received: 28 January 2011 / Accepted: 20 May 2011  Springer-Verlag 2011

Abstract Prebiotics are the non-digestible food ingredients, which help in the successful digestion of the food components in the gut and lower intestine. They play an important role in the promotion of the growth of ‘‘good’’ bacteria in the intestine and gut of humans. In other words, nutraceuticals are beneficial for the maintenance of gut microbiota, microflora, and human health. This study specially reviewed different articles on the role of prebiotics in hepatic encephalopathy, cardiovascular diseases, constipation, diarrhea, hypotriglyceridemia, and type 2 diabetes. In conclusion, prebiotics are supplements to improve health and can favorably treat biological disorders. Keywords

Prebiotics  Gut microflora  Nutraceuticals

Introduction There is an environmental, health and social impacts on the eating habits and trends in food production and consumption. The diet-related problems such as gut complications, ulcerative colitis, irritable bowel syndrome, which result owing to overgrowth and imbalance of intestinal microbial flora, have significant impact on present scenario of health. At birth, the gastrointestinal tract is sterile and after birth when the colonization of the microflora begins in the gastrointestinal tract, its condition depends on the mode of birth, infant nutrition, use of antibiotics, diet, and age. Initially individual’s overall health was determined through

R. Singh (&)  P. K. Sharma  R. Malviya Department of Pharmaceutical Technology, Meerut Institute of Engineering and Technology, Bypass Road, Baghpat Crossing, Meerut 250005, Uttar Pradesh, India e-mail: [email protected]

the gut health. The human gut has following functions: (a) it breaks food particles into useful nutrients (b) it facilitates absorption of nutrients into the blood through intestinal walls and (c) it prevents foreign and toxic molecules from entering into the bloodstream. Therefore, the malfunctioning of gut has a direct and negative impact on human health. Human health depends upon the consumption patterns vary significantly from healthy diets which are rich in fruits and vegetables than rich in animal fat and animal food products. The major difference in European countries is an individual affair, while in continental and southern countries the consumers gave more importance to the social dimension of food and meal sharing [1]. The nutritional consumption is maintained among countries that contributed greatly due to the differences in the health of populations. Mostly the population of most countries is still fighting with the severe diseases of a modern age such as obesity, osteoporosis, cancer, diabetes, allergies, stress, and dental problems. It has been found that aging populations require different types of healthy food products [2]. Therefore, the increased energy uptake, unbalanced diets, and highly processed foods used in fast food product are a huge problem in the population of the different countries [3–6]. Economic crises and high food price tends to favor the unbalanced and ‘‘cheap’’ food intakes which lead health related problems such as obesity in the different countries [7]. It has been observed that diet of an individual in the USA has the highest amount of calories than other countries and the lowest calories around worldwide with the low cost [8] because the USA has the highest availability of large-scale agricultural commodities for refined and processed food products. The recent advancements in the nutritional sciences and natural products like prebiotics have received high attention towards the common population. These functional and medicinal food components

123

Author's personal copy Mediterr J Nutr Metab

play an important role in maintaining the human immune system from specific diseases [9–11]. These functional or medicinal foods hold a great promise in clinical therapy due to their potential to reduce side effects associated with chemotherapy and significant advantages in reducing the health care cost [12]. Nutraceuticals In 1989, Stephen DeFelice, founder and chairman, Foundation for Innovations in Medicine (FIM), Cranford, NJ, coined the term ‘‘nutraceuticals’’, which is a combination of the words, ‘‘nutrition’’ and ‘‘pharmaceutical’’. According to DeFelice, it can be defined as, ‘‘a part of a food that provides medical or health benefits which includes the prevention and/or treatment of a disease’’ [13]. Nutraceuticals are the health promoting, naturally derived bioactive food components containing proteins, lipids, carbohydrates, and other necessary minerals [14, 15]. This term is interchangeable and distinguished by their different points of view due to the specific or strong purposes [11, 16] because these are the dietary substances which are intended to act as a supplement by increasing the total dietary intake of the common ingredients [17]. The nutraceuticals is more well defined dietary supplements such as vitamins, minerals and herbs which are used for the disease prevention and curing [18–20]. According to the scientific term, the vital nutrients are necessary for human body under certain conditions like drug-drug interactions, nutraceuticals-drug interactions, which shows the direct effect on the individual’s health [13, 21]. Nowadays, the nutraceuticals give the benefit or even harmful for health because excess intake of any nutrient may not be benefitted for the human health. This advanced knowledge of nutraceuticals is required to maintain the health of the human body and further providing the standardization of the manufacturing processes and clinical practices adds the more value to the nutraceuticals market [22]. Health benefits of nutraceuticals as functional foods The functional food for first consumer can act as a nutraceuticals for the other consumers. There is a slight difference between functional foods and nutraceuticals [23]. Functional foods are prepared by using ‘‘scientific intelligence’’ with or without the knowledge as to why or how it is being used, whereas nutraceuticals act as functional and health-benefitting food items in several areas like cancer, cardiovascular diseases, atherosclerosis, diabetes, mental health, aging, and immunity response [24]. Thus, functional food provides the required amount of vitamins, fats, proteins, carbohydrates, etc., needed for health and survival [13]. Dietary supplements contain one or more dietary

123

ingredients like vitamins, minerals, herbs or other botanicals [14]. However, nutraceuticals are the active ingredients that are supplied through the diet and aid in the prevention and/or treatment of diseases and disorders [23, 25]. Some phenolic compounds function as antibiotics, natural pesticides, coumarins, carotenoids and enzyme inhibitors are used for the establishment of symbiosis with pollinator attractants, protective agents and plants stabilizer [26]. The anti-carcinogenic effects of phytochemicals in plant foods are varied with a combination of possibilities like anti oxidants effects, cell differentiation, increased activity of enzymes, detoxification of carcinogens, estrogen metabolism change, decreasing cell proliferation and effect on DNA methylation. Nutraceuticals continuously provide the way to reduce the increasing burden on the human health by the continuous preventive measures. The nutraceuticals mainly consists of the plant as well as seafoods as the functional foods because the complementary nature of phytochemical are considered in the formulation of the functional foods and as a choice for the healthy diet. Examples of nutraceuticals are the fortified dairy products like milk, citrus fruits like orange juices [27] nutraceuticals also play significant role in different types of therapies Nutraceuticals have been used for the different therapies of various disorders such as green tea, lycopene, soya, vitamin D and vitamin E [13]. Future scope of these products have high therapeutic potential and well designed clinical trials assessing the combinations of these compounds results in the synergism into human health.

Prebiotics Prebiotics are the low digestible food, fermented ingredient, or a fiber that affect the health of the host beneficially by stimulating the growth and activity of the gastrointestinal microflora and species of bacteria in the colon. It also changes the composition and/or activity of the gastrointestinal microflora resulting in the benefits on the human health and host health [28, 29]. Prebiotics adds the nutritional and nutraceuticals values to the normal food because it forms a group of diverse carbohydrate ingredients that is originated by fermentation process and having direct effect on the health. The bifidogenic oligosaccharides (nondigestible in nature) and galacto-oligosaccharides fulfill the criteria according to the prebiotics classification. These are the non-fermentable carbohydrates, which are poorly digested in the small intestine and stimulate the growth of Bifidobacterium and some Gram-positive bacteria. The major prebiotics which are used as human nutrition are inulin, galacto-oligosaccharides, fructo-oligosaccharides, lactulose, malto-oligosaccharides and resin starch. The

Author's personal copy Mediterr J Nutr Metab

major energy sources are butyrate, propionate, fatty acids, acetate all are the end products of the carbohydrates metabolism. Inulin and oligofructans are found in the chicory, tomatoes, bananas, asparagus, garlic, onion, and many other plant-derived compounds. The naturally occurred prebiotics are chicory, barley, bananas, onion, garlic, berries, honey, artichokes, dairy product, legumes, oatmeal, whole grains, and wheat. The prebiotics is an ingredient that acts as a ‘‘good bacteria’’ in the digestive tract and that help in nourishing an inhospitable environment mainly for the pathogens that may attack the immune system. The best way to keep the immune system strong is to eat the foods that may enhance with the prebiotics especially during winters. Some examples of prebiotics available in the market that helps to improve immune efficiency include Nutra Flora and Nu Vim. Both of these products are the great source of minerals, vitamins, proteins that help in the maintenance of the good health and high energy. Modified prebiotics of the colon causes the predominance of the colonic microflora like lactobacilli and bifidobacteria [30]. A limited number of body functions can causes the positive and psychological effect on the human health [31] through the use of the traditional nutrients [32]. The dietary carbohydrates that escape digestion in the small intestine can undergo bacterial fermentation in the colon. Therefore, during this process the microbial ecology of the gastrointestinal tract has a great influence on the functioning of the gut metabolism. The most promising targets for food functionality are gastrointestinal functions, transit time, bowel activity, mucosal motility, and epithelial cell proliferation but these are associated with the balanced colonic microflora. The nutrient bioavailability mediated gastrointestinal system and systemic activity of lipid homeostasis indirectly affected by nutrient digestion and fermentation [33, 34]. To quantify the inulin and oligofructose in plants and food products the analytical method has been developed by the Association of Official Analytical Chemists like fructans are tested by the ion exchange chromatography method [35, 36]. The natural food ingredients like chicory, inulin, and oligofructans are officially recognized as safe status in the United States. The synthetic inulin type fructans are obtained in presence of enzymes and catalyzed in the presence of fructosyl molecules. The inulin type of fructans are used as sugar substitutes, as a fat replacer, providing texture, stabilizing foam and for improving the mouth feel. It has been used in dairy products; desserts such as jellies, ice creams; bakery products like cookies, breads, pastries, spreads, infant fed and classified as non digestible oligosaccharides [37]. The modulation of microbial community through prebiotics gave a great opportunity to support the human health and well-being [38].

Functional improvements Fate of prebiotics in the gastrointestinal tract Prebiotics are the non-digestible fermentable fibers that are easily fermented by the colonic microflora. The b-configuration of the C-2 in anomeric fructose monomers and inulin type fructans will produce the resistance against the digestion in the upper part of the gastrointestinal tract. Bifidobacteria are the main targetable organism in the prebiotics [39]. Whenever any food ingredient entered into the gastrointestinal tract (git) it is selectively fermented into the mixed culture environment of the git. In most cases prebiotics are directed towards the lactic acid producing micro organism [40]. Prebiotics shown an increase in the numbers of Bifidobacterium but at lesser extent within the gut microflora. Among colonic microflora Bifidobacterium and lactobacilli are the main species which contributed towards the human health [41]. There is evidence that the fructose monomers of inulin type fructans are digested in the upper part of the gastrointestinal tract. These are known as colonic food that enters into the colon and serve to endogenous bacterium that provides the energy. The inulin type of fructans is fermented by the bacteria that help in the colonization in the large bowel. This evidence is supported through in vitro and in vivo correlation which confirms the production of the lactic and short chain carboxylic acids is an end product of fermentation. This fermentation results in the simulative growth of Bifidobacterium population and the prototypes of inulin type of fructans [30]. Effect of prebiotics on mineral absorption The mineral absorption is mainly occurring in small intestine which linked through improvement in the large bowel [42]. Prebiotics has shown its major effects on the bones with bone relevant minerals such as Calcium, magnesium and zinc [43–46]. The impairment of the small intestinal absorption of minerals and non digestible carbohydrates is due to their binding and sequestering action. The sequestered and bounded minerals are not directly absorbed in the small intestine and colon because they directly release and absorbed from the carbohydrate matrix. A high concentration of short chain carboxylic acids results in the colonic fermentation of the non digestible carbohydrates those results in the colonic absorption of minerals particularly Ca2? and Mg2?. The binding or sequestering of minerals and some non digestible carbohydrates improves the mineral absorption and maintains the balance the effect of osmotic pressure into the large bowel thus increase the volume of the fluid in which these minerals can dissolve. Furthermore fermented carbohydrates acidify

123

Author's personal copy Mediterr J Nutr Metab

the colonic content and raise the concentration of the ionized minerals that favors the passive diffusion.

the gastrointestinal tract is due to the altered microbial exposure and allergic diseases are become more prompt [57].

Effect on the metabolism of lipids In triglyceridemia the inulin type of fructans decrease the serum level of lipids in the healthy humans [47]. In hypotriglyceridemic patients the concentration of plasma very low density lipoproteins (VLDL) is mostly decreased due to the modifications in the free fatty acids concentrations in the serum level of the humans resulting in the decrease of the hepatic synthesis of the triacylglycerol containing lipoproteins [48]. The lipogenesis in the liver causes the reduction in the lipogenic enzyme activity which reduces the VLDL triacylglycerol secretion in the fructan fed organisms. The effect of inulin type fructans causes the modulation in the triacylglycerol metabolism which shows two effects: (1) Modification in the concentration of glucose or insulin and (2) effect is the production of short chain carboxylic acids in large bowel. These effects are due to the increased gene transcription and the dietary modulation which are linked to the physiologic changes [49]. The long term administration of the oligofructans decreases the total cholesterol concentrations and bile acids in the hypotriglyceridemic patients [50]. Reduction in the disease risk The prebiotics are reduces the risk of diseases such as: • • •



Constipation relief that results due to the fecal bulking and intestinal motility. Suppression of diarrhea associated with intestinal infections. Reduction of risk of osteoporosis results in the improvement of bioavailability of calcium and minerals. Reduction in the risk of cardiovascular disease associated with dyslipidemia.

The hypertriglyceridemic effects show the insulin resistance which is associated with the hyper energetic and high carbohydrates feeding in humans resulting in the reduction in the risk of obesity and type 2 diabetes. Researches have been carried out on the inulin and oligofructans to reduce the risk of carcinogenic activity of azoxymethane and dimethylhydrazine [51, 52]. Prebiotics are act as functional food which shows the cancer inhibitory effects in identifying the potential implications for the human health [33]. Food hypersensitivity and allergic diseases may be increasing in the developed countries day by day [53–56]. Asthma and rhinoconjunctivitis are becoming prevalent more in childhood. The prebiotics should escape digestion and absorption in the upper part of

123

Effects of prebiotics on intestinal microflora The microflora of a gastrointestinal tract acts as a natural resistance factor. Prebiotics are also fermentable oligosaccharides that are designed to change the composition activity for the promotion of the host health. The acidification of the colonic contents forms the short chain fatty acids which play an important role in cellular process regulation [58]. The certain products of bacterial metabolism (e.g. butyrate) could provide the further therapeutic tools in a sector of the treatment which has long proved difficulties [59]. The prebiotics modulate both the immunity and intestinal systems through the association of gut microflora. In the gut the prebiotics improves resistance in colonization and risk of pathogen translocation. Both gastrointestinal tract and systemic immunity helps in the enhancement of the pathogenic resistance in the git and this will reduce the risk of infections throughout the body [60]. It has been found that administration of the non digestible food stimulate the growth or the activity of the limited kind of bacteria in the colon. The natural example of the infant nutrition is the breast feeding. The prebiotics approach is an important physiologic approach which influences the intestinal microflora in several ways. Several evidences demonstrate the administration of the different prebiotics like inulin, fructo-oligosaccharides that induces a modification in intestinal microflora resulting in improvement in the number of Bifidobacterium and lactic acid bacteria. The primary effect of the prebiotics in the gastrointestinal tract is to modify the fermentative capacity of the intestinal flora. For example constipation relief was obtained in chronically constipated condition in the intestinal flora when individuals are treated with inulin. Prebiotics play an important role in increasing the mineral absorption like calcium and magnesium as observed in the many animal models [61, 62] but not studied with iron and zinc. In human diet the short chain fructans increase the absorption of magnesium and less effect on calcium [63]. Oligofructase, oligofructose and inulin are well tolerated and enhanced effect of absorption of calcium [64, 65]. The administration of prebiotics showed an effect on cholesterol level in adults and on clinical endpoints of infectious episodes or allergy. The dietary supplementation with a specific mixture of oligosaccharides modulated during the early phase of an immune response during the vaccination. This is due to an increase in the vaccine-specific DTH responses (delayed type hypersensitivity) which comes

Author's personal copy Mediterr J Nutr Metab

after continuous supplementation from 14 to 30 days of the dietary foods with the oligosaccharide mixture. This prolonged effect on the microbiota caused the effect on the DTH response and partial overlap with a developing immune modulatory effect during these studies [66]. Relations between prebiotics, microflora and health The human activities are suppressed or enhanced by the activity of the intestinal microflora. The health promoting bacterial groups are lactobacilli and bifidobacteria they increase the beneficial bacterial activities in the human intestine. The term prebiotics was coined in the presence of inulin and oligofructase due to the stimulation of the Bifidobacterium in the colon [67]. The features of prebiotics are as: (a) it is neither hydrolyzed nor absorbed in the upper part of the intestinal tract, (b) it favors small number of the endogenous micro biota, (c) induce the luminal or systemic effects that are beneficial to the health of the host [68].The stimulation of these bacterias are advantageous because it inhibits the growth of the pathogens, reduces formation of ammonia, lower the blood cholesterol levels and the restore the normal flora during the antibiotics therapy [69]. The non-digestible oligosaccharides or lactulose stimulate bacterial fermentation in the proximal colon resulting in the formation of the short chain fatty acids resulting in decreases the luminal pH [70]. The low pH stimulates the growth of the lactobacilli and Bifidobacterium which is well adapted to this pH. The randomized trials with the prebiotics not only modify the intestinal flora but also show its beneficial effects. The breast-fed infant has complex microbiota which is mainly dominated by Bifidobacterium. The primary source of the micro-organisms in the breastfed infant had comes from the maternal vaginal and fecal flora. The intestinal microflora modifications include age, type of delivery, diet, immune system, gastric pH and use of antibiotics. In human number of intestinal microflora depends upon various factors like development of intestinal barrier, short chain fatty acid bile acid transformation and synthesis of vitamins. The germ free animals lack the normal and infiltrate sub mucosal layers because their lymphoid structures are not well developed and serum immunoglobulin is low. The suppressor cell activity is also absent and animals are not well tolerated to antigens which is given through the parental route. The microbiotic disruption due to the antibiotic administration in the animals shows an alteration in the immune regulation in the airways leading to the up-regulation in response to the different antigens [71]. Fewer Bifidobacterium, clostridia and lactobacillium eventually develop the microbiological imprinting and the risk of immune related diseases [72]. When prebiotics were administered in neonates and allergic adults, the little aggregated effects were shown by the

intestinal bacteria and the immune system [73, 74]. This process occurs in the age frame system and shows the imprinting effects on the immune system in the early stages of life and after delivery [75]. Results also showed that prebiotics provide protection against colorectal cancer (CRC) [76]. From some studies it has been postulated that prebiotics and probiotics reduce the toxic effect in the gut and give protection against colonic tumor development [77, 78]. Prebiotics used in the treatment of hepatic encephalopathy Hepatic encephalopathy is a group of complications in a central nerve system function due to hepatic insufficiency [79]. It is a multifactorial design even after minimal impact on the patient’s life [80, 81]. Our intestinal flora contains the ammonia and several urease positive bacterial species [82]. In humans, urea is the mainly produced from the ammonia and carbon dioxide through the urea cycle [83, 84]. Lactulose, a non-absorbable, synthetic disaccharide, has multiple effects on gut microflora. Fermentation of lactulose yields lactic acid and butyric acid and some gasses specially H2. Following the production of H2 in the colon, the colonic stasis increases due to the ammonia uptake. Therefore, the lactulose shows its main effect in the rapid stool transit due to the activation of the gas-mediated bacteria of intestinal peristalsis [85, 86]. In liver encephalopathy, the intestine plays an important role to reduce colonic bacteria. For bowel cleansing, the following principles are: 1. 2. 3.

Use a variety of laxatives, non-absorbed disaccharides. Be aware of disabilities and observe enemas. Isotonic mannitol, for oral git bleeding, is effective in hepatic encephalopathy.

The non-disaccharides drugs are commonly used for reducing the blood-ammonia levels in hepatic encephalopathy patients. The treatment of lactilol is better in hepatic encephalopathy and non-absorbed antibiotic is neomycin (3–6 g/day, three times/day) for long time use in patients having persistent hepatic encephalopathy. Prebiotics are useful in promoting active ingredients, which help in reducing the nitrogen load. The prebiotics reduce the growth of bacteria and absorb the toxins produced by harmful bacteria leading to health improvement in hepatic encephalopathy. The benzodiazepines receptor antagonists, flumazenil and naloxone, as well as semi-synthetic ergot alkaloid derivatives, are the drugs for treatment. Currently, there is no effective treatment for hepatic encephalopathy, but drug therapy is one of the most important treatments (http://www.healthwritings.com). The lactulose shows the multiple effects on the gut flora and intestine because it is a

123

Author's personal copy Mediterr J Nutr Metab

non-digestible food supplement required in the small bowel that affects beneficially due to its fermentation in the colonic bacteria on the health of the host. In the same way glucose, sucrose and lactose easily fermented in the small bowel especially Bacteroides species in the colon. The fermentation of lactulose yields lactic acids, acetic acid, butyric acids, and molecular hydrogen. The molecular hydrogen which is obtained through the fermentation of lactulose is excellent substrates for the colonocytes and for the fecal flora. This hydrogen molecule produced from single monosaccharides moiety and used in the removal of the unusual colonic bacteria [87]. The ammonia-producing bacteria and urease positive bacteria are lost due to the synthesis of this hydrogen molecule and resulting in reduction of ammonia uptake in the intestine. The main effect of the lactulose is the rapid transit of the stool due to the rapid action of bacteria and intestinal. Prebiotics and gut microbiota Prebiotics are the non-digestible food ingredients mostly oligosaccharides which affect the host beneficially by stimulating growth, activity or both of intestinal bacteria. The criteria to fulfill the needs of the prebiotics include the resistance against gastric acidity and specific mammalian enzymes, susceptibility against fermented gut bacteria and stimulate the growth of beneficial intestinal bacteria. The beneficial effect of prebiotics include the control of intestinal transit time and bowel habits, reduction of risk of arthrosclerosis, osteoporosis, obesity, type 2 diabetes,

Table 1 Dose of some prebiotics

123

S. No.

cancer, and allergies [88]. The intestinal microflora and gut microflora plays an important role in the development of local and systemic immune response during the early stages of life. The nutritional ingredients related to the prebiotics have been added to infant formula is an attempt to make its composition similar to that of human milk. Through these studies has been concluded that use of prebiotics may increase the resistance to intestinal and extra intestinal pathogens through the modulation of the immune system and causes the reduction in allergic diseases [89]. When galacto-oligosaccharides and fructo-oligosaccharides are combined with each other they promote the growth of the intestinal microbiota, e.g., bifidobacteria. They also promote the microbiota composition and increase the amount of the fecal bifidobacteria which favor the Bifidobacterium composition that is similar to breast feeding infant [90, 91]. The GOS bind the pathogenic sites that coat the surface of gastrointestinal epithelial cells which inhibit the enteric pathogen adhesion [92]. The mammalian digestive enzymes and their ability to stimulate the growth of colonic bacteria are increase with their biological diversity and structural resistance [61, 68, 69, 93, 94]. The prebiotics effects on the immune system are due to the induction in the gut microbiota and the generation of the short chain fatty acid (SCFA) receptors on leucocytes [70]. The long chain inulin shows their effects on the bowel inflammation which reduce the pro-inflammatory markers, along with an increase in the intestinal bifidobacteria and lactobacilli [71, 72]. The SCFA receptors include the regulation of the intestinal fat absorption which impairs the lipid transport along the cells

Ingredients

Dose

1.

Galacto-oligosaccharides (GOS) [101]

2–3 g/day

2.

Inulin [102]

2–12 g/day (European diet), 5–8 g/ day (Belgium), 7–12 g/day (Spain)

3.

Xylo-oligosaccharides (XOS) [103, 104]

4 g in a 3-week period, 0.7 g

4.

Lactulose [105]

0.5% in infants formulation

5.

Fructo-oligosaccharides (FOS) [106, 107]

2–12 g/day

6.

Inulin type fructans [108]

8–10 g/day

7.

Oligosaccharides [109, 110]

10 g/L (acidic) 1 g/L(acidic)

8.

GOS/FOS mixture [111]

0.4 g/100 mL or 0.8 g/100 mL

9.

Polydextrose (http://www.scientistlive.com)

4–12 g/day

10.

Dietary fibers [112]

25–30 g in adults

11.

Dietary carbohydrates [74]

10–60 g/day

12.

Inulin type fructans (Crohn’s disease patients) [113]

15 g/day

13.

Inulin type fructans (pubertal males and females) [114, 115]

8 g/day

14.

Lactulose (postmenopausal women) [116]

10 g/day

15.

Xylo-oligosaccharides (pregnant women) [117]

4.2 g/day

Author's personal copy Mediterr J Nutr Metab

[73, 74]. Inulin type fructans and soluble dietary fibers are directly modulated in the bowel that slows down the gastric emptying, transit time and absorption of glucose [75]. Inulin type of fructans and dietary fibers like cellulose, dextrins, chitins, pectins, and waxes can modulate the transit time through the gut. The bacterial fermentation may induce the changes in bacterial populations and shows the improvements in the gut function through in vitro and in vivo correlation [92, 95–97]. The microbial colonization of human intestine begins at birth. The kind of delivery has a great impact on the composition of the intestinal flora in the first days of life. Therefore, the microflora is mainly influenced by the type of feeding mainly breast-fed infants show predominance against bifidobacteria and lactobacilli, whereas the bottle-fed infants develop predominance against mixed flora with a lower number of bifidobacteria. The ‘‘bifidogenic effect’’ of human milk is not related to a single growthpromoting substance. The prebiotics effect has been described at low concentration of proteins and phosphates this show the presence of lactoferrin, lactose, nucleotides and oligosaccharide [98].

Dose of prebiotics Prebiotics are used in food industries as functional ingredients in beverages, milk products, yogurts, and symbiotic products [99]. The recommended daily dose of the prebiotics depends upon pathologic indication at every level that does not cause any side effect [100]. The major prebiotics inulin, galacto-oligosaccharides, lactulose, and fructo-oligosaccharides, play significant roles in functional foods and nutritional supplement. The dose of some recommended prebiotics is shown in Table 1.

Conclusion The whole study shows that there is a strong relationship between gut microflora and colonic bacteria in the human intestine. Prebiotics have been used as health promoters for a long time. One of the important properties of nutraceuticals is their non-toxic effect. They are cheap and effective. The future trends in prebiotics will lead to the development of the healthy individual and lifestyle. Directly and indirectly, prebiotics promote health. In future, nutraceuticals can provide cheap, effective, less harmful disease modifiers in the health profession. Acknowledgments Authors are highly thanks full to Department of Pharmaceutical Technology, Meerut Institute of Engineering and Technology for providing necessary guidance and facilities. Authors would like to thanks NISCAIR (National Library) New Delhi for providing library facilities.

Conflict of interest

None.

References 1. Bronzwaer S (2008) EFSA scientific forum ‘‘from safe food to healthy diets’’. EU risk assessment—past present and future. Trends Food Sci Technol 19:S2–S8 2. Roberts SB, Rosenberg I (2006) Nutrition and aging: changes in the regulation of energy metabolism with aging. Physiol Rev 86:651–667 3. Perez-Cueto FJ, Verbeke W, de Barcellos MD, Grunert KG et al (2009) Food-related lifestyles and their association to obesity in five European countries. Appetite 54:156–562 4. Gilbert RL, Mielke JH (eds) (1985) The analysis of prehistoric diets. Academic Press, Orlando, pp 622 5. Eaton SB, Eaton SB III, Konner MJ, Shostak M (1996) An evolutionary perspective enhances understanding of human nutritional requirements. J Nutr 126:1732–1740 6. Eaton SB, Eaton SB III, Konner MJ (1997) Paleolithic nutrition revisited: a twelve-year retrospective on its nature and implications. Eur J Clin Nutr 51:207–216 7. Roskam AJ, Kunst AE, Van Oyen H et al (2009) Comparative appraisal of educational inequalities in overweight and obesity among adults in 19 European countries. Int J Epidemiol (Epub ahead of print) 8. Crawford MA, Marsh D (1995) Nutrition and evolution. Keats Publishing, New Canaan 9. Bland JS (1996) Phytonutrition, phytotherapy, and phytopharmacology. Altern Ther Health Med 2:73–76 10. Berger MM, Shenkin A (2006) Vitamins and trace elements: practical aspects of supplementation. Nutrition 22:952–955 11. Bagchi D (2006) Nutraceuticals and functional foods regulations in the United States and around the world. Toxicol 221:1–3 12. Ramaa CS, Shirode AR, Mundada AS, Kadam VJ (2006) Nutraceuticals—an emerging era in the treatment and prevention of cardiovascular diseases. Curr Pharm Biotechnol 7:15–23 13. Brower V (1998) Nutraceuticals: poised for a healthy slice of the healthcare market? Nat Biotechnol 16:728–731 14. Zeisel SH (1999) Regulation of ‘‘Nutraceuticals’’. Science 285:185–186 15. Whitman M (2001) Understanding the perceived need for complementary and alternative nutraceuticals: lifestyle issues. Clin J Oncol Nurs 5:190–194 16. Koletzko B, Aggett PJ, Bindels JG et al (1998) Growth, development and differentiation: a functional food science approach. Br J Nutr 80(Suppl):5–45 17. Halsted CH (2003) Dietary supplements and functional foods: 2 sides of a coin? Am J Clin Nutr 77:1001S–1007S 18. FDA/CFSAN resources page. Food and Drug Administration Web site. Dietary Supplement Health and Education Act of 1994. Available at: http://vm.cfsan.fda.gov/dietsupp.html 19. DeFelice SL (2002) FIM Rationale and Proposed Guidelines for the Nutraceutical Research & Education Act (NREA), November 10. Foundation for Innovation in Medicine. Available at: http://www.fimdefelice.org/archives/arc.researchact.html 20. Ross S (2000) Functional foods: the Food and Drug Administration perspective. Am J Clin Nutr (Suppl) 71:1735–1738 21. Iriti M, Vitatini S, Fico G et al (2010) Neureoprotective herbs and foods from different traditional medicines and diets. Molecules 15:3517–3555 22. Gidley MJ (2004) Naturally functional foods—challenges and opportunities. Asia Pac J Clin Nutr 13(Suppl):31 23. Kalra EK (2003) Nutraceuticals—definition introduction. AAPS Pharm Sci 5:2–3

123

Author's personal copy Mediterr J Nutr Metab 24. Food and Agriculture Organisation of the United States (FAO). Report on Functional Foods, Food Quality and Standard Service (AGNS), 2007. Available online: http://www.fao.org/ag/agn/ agns/files/Functional_Foods_Report_Nov2007.pdf (accessed on February 2010) 25. FDA/CFSAN resources page. Food and Drug Administration. Dietary Supplement Health and Education Act of 1994. Available from: http://www.consumermanitoba.ca/resources.html 26. Shahidi F, Naczk M (2004) Phenolics in food and nutraceuticals. CRC Press, Boca Raton 27. Kalra EK (2003) Nutraceuticals—definition and introduction. AAPS Pharm Sci 5:25. Available online: http://www.aapsj. org/view.asp. (accessed on 25 February 2010) 28. De Vrese M, Schrezenmeir J (2008) Probiotics, prebiotics, and synbiotics. Adv Biochem Eng Biotechnol 111:1–66 29. Douglas LC, Sanders ME (2008) Probiotics and prebiotics in dietetics practice. J Am Diet Assoc 108:510–552 30. Gibson GR, Roberfroid MB (1995) Dietary modulation of the human colonic microflora: introducing the concept of prebiotics. J Nutr 125:1401–1412 31. Bellisle F, Diplock AT, Hornstra G et al (1998) Functional food science in Europe. Br J Nutr 80(Suppl):S3–S4 32. Clydesdale F (1997) A proposal for the establishment of scientific criteria for health claims for functional foods. Nutr Rev 55:413–422 33. Roberfroid MB (2000) Concepts and strategy of functional food science: the European perspective. Am J Clin Nutr 71(Suppl):1660S–1664S 34. Roberfroid MB (1996) Functional effects of food components and the gastrointestinal system: chicory fructooligosaccharides. Nutr Rev 54:S38–S42 35. Hoebregs H (1997) Fructans in foods and food products, ionexchange chromatographic method: collaborative study. J Assoc Off Anal Chem Int 80:1029–1037 36. Van Loo J, Coussement P, De Leenheer L et al (1995) On the presence of inulin and oligofructose as natural ingredients in the western diet. Crit Rev Food Sci Nutr 35:525–552 37. Cummings JH, Roberfroid MB (1997) A new look at dietary carbohydrate: chemistry, physiology and health. Eur J Clin Nutr 51:417–442 38. Blaut M (2002) Relationship of prebiotics and food to intestinal microflora—an introduction. Eur J Nutr 41. doi:10.1007/s00394002-1102-7 39. Drasar BS, Roberts AK (1990) Control of the large bowel microflora. In: Hill MJ, Marsh PD (eds) Human microbial ecology. CRC Press, Boca Raton, pp 87–111 40. Park SF, Kroll RG (1993) Expression of listeriolysin and phosphatidylinositol-specific phopholipase C is repressed by the plant derived molecule cellebiose Listeria monocytogenes. Mol Microbiol 86:53–61 41. Tannock GW (2002) Probiotics and prebiotics: where we are going? In: Tannock GW (ed) Probiotics and prebiotics: where we are going? Caister Academic Press, Wymondham, pp 1–20 42. Roberfroid MB (2000) Prebiotics and probiotics: are they functional foods? Am J Clin Nutr 71:1682S–1687S 43. Scholz-Arhens KE, Schaafsma G, Schrezenmeir J et al (2001) Effects of prebiotics on mineral metabolism. Am. J Clin Nutr 73:2(Suppl4):59S–64S 44. Scholz Ahrens KE, Schrezenmeir J (2002) Inulin, oligofructose and mineral metabolism-experimental data and mechanism. Br J Nutr, 87(Suppl2):S179–S186 45. Coudary C, Demigne C, Rayssiguier Y (2003) Effects of dietary fibres on magnmesium absorption in animals and humans. J Nutr 133:1–4 46. Cashman K (2003) Prebiotics and calcium bioavailability. Curr Issues Intest Microbiol 4:21–32

123

47. Reddy BS, Rivenson A (1993) Inhibitory effect of Bifidobacterium longum on colon, mammary and liver carcinogenesis induced by 2-amino-3 methylimidazol[4, 5-f]quinoline, a food mutagen. Cancer Res 53:3914–3918 48. Fiordaliso M, Kok N, Desager JP et al (1995) Dietary oligofructose lowers triglycerides, phospholipids and cholesterol in serum and very low density lipoproteins of rats. Lipids 30:163–167 49. Takase S, Goda T, Watanabe M (1994) Mono stearyl glycerolstarch complex: its digestibility and effects on glycemic and lipogenic responses. J Nutr 40:23–36 50. Davidson MH, Maki KC, Synecki C et al (1998) Evaluation of the influence of dietary inulin on serum lipids in adults with hypercholesterolemia. Nutrition 18:503–517 51. Reddy DS, Hamid R, Rao CV (1997) Effect of dietary oligofructose and inulin on colonic preneoplastic aberrant crypt foci inhibition. Carcinogenesis 18:1371–1374 52. Rowland IR, Rumney CJ, Coutts JT, Lievense LC (1997) Effect of Bifidobacterium longum and inulin on gut bacterial metabolism and carcinogen-induced crypt foci in rats. Carcinogenesis 19:281–285 53. Burr ML, Butland BK, King S, Vaughan Williams E (1989) Changes in asthma prevalence: two surveys 15 years. Arch Dis Child 64:1452–1456 54. Halken S (2004) Prevention of allergic disease in childhood and epidermiological aspects of primary and secondary allergy prevention. Pediatr Allergy Immunol 15(Suppl 16):4–5 55. Presscott HM, Apajalahati JH, Rautonen N, Stowell J et al (2004) Polydextrose, lactitol and fructo oligosaccharides fermentation by colonic bacteria in a three stage continuous culture system. Appl Environ Microbiol 70:4505–4511 56. Schultz Larsen F (1996) Atopic dermatitis: an increasing problem. Pediatr Allergy Immunol 7:51–53 57. Holt PG, Sly PD, Bjorksten B (1997) Atopic versus infectious diseases in childhood: a question of balance? Pediatr Allergy Immunol 8:53–58 58. Blaut M (2002) Eur J Nutr 41(Suppl1):111–116 59. Gasbarrini G, Montaltoa M, Assisi R (1999) The role of bacterial flora and its products in the functioning of the small Intestine Digestive and Liver Disease Supplements 1 (translation). Ital J Gastroenterol Hepatol 31:481–488 60. Kleessen B, Blaut M (2005) Modulation of gut mucosal biofilms. Br J Nutr 93(Suppl 1):S35–S40 61. Roberfroid MB (2007) Prebiotics: the concept revisited. J Nutr 137:830S–837S 62. Haarman M, Knol J (2005) Quantitative real-time PCR assays to identify and quantify fecal Bifidobacterium species in infants receiving a prebiotic infant formula. Appl Environ Microbiol 71:2318–2324 63. Scholtens PA, Alles MS, Bindels JG, Knol J et al (2006) Bifidogenic effects of solid weaning foods with added prebiotic oligosaccharides: a randomised controlled clinical trial. J Pediatr Gastroenterol Nutr 42:553–559 64. Shoaf K, Mulvey GL, Armstrong GD, Hutkins RW (2006) Prebiotics galactooligosaccharides reduce adherence of enteropathogenic Escherichia coli to tissue culture cells. Infect Immun 74:6920–6928 65. Gibson GR, Wills CL, Van Loo J (1994) Non-digestible oligosaccharides and bifidobacteria implication for health. Int Sugar J 96:381–387 66. Arjan PV, Jan K, Bernd S et al (2010) Specific prebiotic oligosaccharides modulate the early phase of a murine vaccination response. Int Immunopharmacol 10:619–625 67. Mizota T (1996) Functional and nutritional foods containing bifidogenic factors. Bull Int Dairy Found 313:31–35

Author's personal copy Mediterr J Nutr Metab 68. Gibson GR, Wang X (1994) Regulatory effect of bifidobacteria on the growth of other colonic bacteria. J Appl Bacteriol 77:412–420 69. Kleessen B, Hartman L, Blaut M (2001) Oligofructose and long chain inulin influence the gut microbial ecology of rats associated with a human faecal flora. Br J Nutr 86:291–300 70. Watzl B, Girrbach S, Roller M (2005) Inulin, oligofructose and immunomodulation. Br J Nutr 93:S49–S55 71. Videla S, Vilaseca J, Antolin M et al (2001) Dietary inulin improves distal colitis induced by dextran sodium sulfate in the rat. Am J Gastroenterol 96:1486–1493 72. Welters CF, Heineman E, Thunnissen FB et al (2002) Effect of dietary inulin supplementation on inflammation of pouch mucosa in patients with an ileal pouch-anal anastomosis. Dis Colon Rectum 45:621–627 73. Hoentjen F, Welling G, Harmsen H et al (2005) Reduction of colitis in HLA-B27 transgenic rats is associated with microflora changes and immunomodulation. Inflamm Bowel Dis 11:977–985 74. Lindsay JO, Whelan K, Stragg AJ et al (2006) Clinical, microbiological, and immunological effects of fructo-oligosaccharide in patients with Crohn’s disease. Gut 55:348–355 75. Leenen CHM, Dieleman L (2007) Inulin and oligofructose in chronic inflammatory bowel disease. J Nutr 137:2572S– 2575S 76. Burns AJ, Rowland IR (2000) Anti carcinogenicity of prebiotics and probiotics. Curr Issues Intest Microbiol 1:13–24 77. Gallahar DD, Khil J (1999) The effect of synbiotics on colon carcinogenesis in rats. J Nutr 129:1483S–1487S 78. Reddy BS (1999) Possible mechanisms by which pro and prebiotics influence colon carcinogenesis and tumor growth. J Nutr 129:1478S–1482S 79. Blei A, Cordoba J (2001) Hepatic encephalopathy. Am J Gastroenterol 96:1968–1976 80. Groenweg M, Quero JC, De Bruijn I et al (1998) Subclinical hepatic encephalopathy impairs daily functioning. Hepatology 28:45–49 81. Weissenborn K, Ennen JC, Schomerus H, Ruckery N, Hecker H (2001) Neuropsychological characterization of hepatic encephalopathy. J Hepatol 34:768–773 82. Solga SF (2001) Probiotics can treat hepatic encephalopathy. Med Hypotheses 61:307–313 83. Vogels GD, Van der Drift C (1977) Degradation of purines and pyrimidines. Bacteriol Rev 40:403–468 84. Bongaerts GPA, Vogels GD (1976) Uric acid degradation by Bacillus fastidiosus strains. J Bacteriol 125:689–697 85. Cherbut C (2003) Motor effects of short-chain fatty acids and lactate in the gastrointestinal tract. Proc Nutr Soc 62:95–99 86. Bongaerts G, Severijnen R, Timmerman H (2005) Effects of antibiotics, probiotics and prebiotics in the treatment of hepatic encephalopathy. Med Hypotrheses 64:64–68 87. Marcil V, Delvin E, Garofalo C, Levy E (2003) Butyrate impairs lipid transport by inhibiting microsomal triglyceride transfer protein in Caco-2 cells. J Nutr 133:2180–2183 88. Borthakur A, Saksena S, Gill RK et al (2008) Regulation of monocarboxylate transporter 1 (MCT1) promoter by butyrate in human intestinal epithelial cells: involvement of NF-kappa pathway. J Cell Biochem 103:1452–1463 89. Bruzzese E, Volpicelli M, Squaglia M, Tartaglione A et al (2006) Impact of prebiotics on human health digestive and liver disease 38(Suppl):S283–S287 90. Roberfroid MB (2005) Introducing inulin-type fructans. Br J Nutr 93:S13–S25 91. Napolitano A, Costabile A, Martin-Pelaez S et al (2009) Potential prebiotics activity of oligosaccharides obtained by enzymatic conversion of durum wheat insoluble dietary fibre

92.

93.

94.

95.

96.

97.

98.

99.

100.

101.

102. 103.

104.

105.

106.

107.

108.

109.

110.

into soluble dietary fiber. Nutr Metab Cardiovasc Dis 19:283– 290 Howard MD, Gordon DT, Garleb KA, Kerley MS (1995) Dietary fructooligosaccharide, xylooligosaccharide and gum arabic have variable effects on cecal and colonic microbiota and epithelial cell proliferation in mice and rats. J Nutr 125:2604–2609 Roberfroid MB, Van Loo JAE, Gibson GR (1998) The bifidogenic nature of chicory inulin and its hydrolysis products. J Nutr 128:11–19 Levrat MA, Re´me´sy C, Demigne´ C (1991) High propionic-acid fermentations and mineral accumulation in the cecum of rats adapted to different levels of inulin. J Nutr 121:1730–1737 Napolitano A, Costabile A, Martin-Pelaez S et al (2009) Potential prebiotic activity of oligosaccharides obtained by enzymatic conversion of durum wheat insoluble dietary fibre into soluble dietary fibre. Nutr Metab Cardiovasc Dis 19:283– 290 Durmic Z, Pethic DW, Pluske JR, Hampson DJ (1998) Changes in bacterial populations in the colon of pigs fed different sources of dietary fibre, and the development of swine dysentery after experimental infection. J Appl Microbiol 85:574–582 Go´mez-Conde MS, Garcia J, Chamorro S, Eiras P et al (2007) Neutral detergent-soluble fiber improves gut barrier function in twenty five-day-old weaned rabbits. J Anim Sci 85:3313–3321 Coppa GV, Zampini L, Galeazzi T, Gabrielli O (2006) Prebiotics in human milk: a review digestive and liver disease 38(Suppl):S291–S294 Gibson GR, Roberfroid MB (1995) Dietary modulation of the human colonic microbiota—introducing the concept of prebiotics. J Nutr 125(6):1401–1412 De Souza VMC, Santos SF, Sgarbieri C (2011) The importance of prebiotics in functional foods and clinical practice. Food Nutr Sci 2:133–144 Carabin IG, Flamm WG (1999) Evaluation of safety of inulin and oligofructoseas. Dietary fibre. Regul Toxicol Pharmacol 30(3):268–282 Modler HW (1994) Bifidogenic factors—sources, metabolism and applications. Int Dairy J 4(5):383–407 Chung Y, Hsu C, Ko C, Chan Y (2007) Dietary Intake of Xylooligosaccharides improves the intestinal microbiota, Feed moisture and pH value in the elderly. Nutr Res 27(12):756–761 Nagendra R, Vishwanathan S, KumarS A, MurthyB K, Rao SV (1995) Effects of feeding milk formula containing lactulose to infants on fecal bifidobacterialflora. Nutr Res 15(1):15–24 Passos LML, Park YK (2003) Fructooligosaccharides: implications in human health being and use in foods. Ciencia Rural 33(2):385–390 Tuohy KM, Rouzaud GCM, Bruck WM, Gibson GR (2005) Modulation of the human gut microflora towards improved health using prebiotics—assessment of efficacy. Curr Pharm Des 11(1):75–90 Tahiri M, Tressol JC, Arnaud J et al (2001) Five-week intake of short-chain fructooligosaccharides increases intestinal absorption and status of magnesium in postmenopausal women. J Bone Miner Res 16:2152–2160 Boehm G. Stahl B, Oligosaccharides (2003) In: Mttila-Sandhlm T (ed) Functional dairy products. Woodhead Publ., Cambridge, pp 203–243 Moro G, Minoli I, Mosca M et al (2002) Dosage related bifidogenic effects lof galactooligosaccharides and fructo oligosaccharides in formula fed ferm infants. J Pediatr Gastroenterol Nutr 34:291–295 Jie Z, Bang-Yao L, Ming-Jie X, Hai-Wei L, Zu-Kang Z, TingSong W et al (2000) Studies on then Effects of polydextrose intake on physiologic functions in Chinese people. Am J Clin Nutr 72(6):1503–1509

123

Author's personal copy Mediterr J Nutr Metab 111. H. Tomomatsu (1994) Health effects of oligosaccharides. Food Technol 48(10):61–65 112. Englyst HN, Cummings JH (1987) Digestion of polysaccharides of potato in the small intestine of man. Am J Clin Nutr 45:423–431 113. Griffin IJ, Davila PM, Abrams SA (2002) Non-digestible oligosaccharides and calcium absorption in girls with adequate calcium intakes. Br J Nutr 87(Suppl 2):S187–S191 114. Abrams SA, Griffin IJ, Hawthorne KM (2005) A combination of prebiotic short- and long-chain inulin-type fructans enhances calcium absorption and bone mineralization in young adolescents. Am J Clin Nutr 82:471–476

123

115. Van den Heuvel EG, Muijs T, Van Dokkum W, Schaafsma G (1999) Lactulose stimulates calcium absorption in postmenopausal women. J Bone Miner Res 14:1211–1216 116. Tateyama I, Hashii K, Johno I (2005) Effect of xylooligosaccharide intake on severe constipation in pregnant women. J Nutr Sci Vitaminol 51:445–448 117. Livesey G (2003) Health potential of polyol as sugar replacers, with emphasis on low glycaemic properties. Nutr Res Rev 16:163–191