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Xylitol, an Emerging Prebiotic: A Review

 


Yogita Lugani, Balwinder Singh Sooch*
 Enzyme Biotechnology Laboratory, Department of Biotechnology, Punjabi University, Patiala-147002, Punjab, India

ABSTRACT

 Prebiotics are non-digestible food supplements which continue to gain interest due to various health promising benefits. They change the gut microbiota and prevent common disorders such as obesity, cancer, hypertension, inflammatory bowel disease, diarrhea, constipation, osteoporosis, cardiovascular disorders, diabetes, hypertension, hypercholesterolemia and various allergies. The life style and food habits of humans have been changed with the advancement of technology in this era which cause various gut related disorders. Hence, there is need of fibers enriched diet to regulate the healthy gut microbiota. The focus of scientists is now towards the use of symbiotic (combination of prebiotics and probiotics) to regulate the healthy gut microbiota. Many food industries have focused on discovering new prebiotics along with nutraceutical and pharmaceutical properties. The relationship between gut microbiota, health status and effect of drugs and antibiotics in humans can be explored by understanding the genomics, metabolomics and system biology. The use of in silico tools further improves the understanding of effect of these prebiotics in maintaining the healthier microbiota and for developing new prebiotics. This review paper discusses the types of prebiotics, their mode of action, applications, safety issues and potential of xylitol as emerging prebiotic.

Keywords: Prebiotic, Xylitol, Application, Safety issues, Microbiota.

INTRODUCTION

 The term prebiotic was firstly introduced by Gibson and Roberfroid in 1995 1 and it is defined as “a non-digestible food ingredient which beneficially affects the host by selectively simulating the growth and/or activity of one or a limited number of bacteria in the colon and thus improving host health”. The food ingredient is classified as prebiotic when it is not absorbed or hydrolyzed in the stomach or small intestine, promotes the growth of beneficial micro flora and alter the micro flora to a healthy composition with beneficial systemic effects within the host 2. The food ingredient is classified as prebiotic by many criteria such as safety, stability, organoleptic property, resistance to digestion in the upper bowel, fermentability in the colon and ability to improve the growth of useful bacteria in the gut 3. Prebiotics when combined with probiotics have additive and synergistic effect in providing better healthy condition 4-5. Prebiotics, probiotics and symbiotic are active components of functional foods with significant positive influences on human and animal well beings. The term functional food was defined in 1984 by researchers of Japan and it is defined as foods which improve the overall condition of body and reduce the chances of infection 6-7. There are many unique features of a functional food like normally consumed as a part of human diet with positive effects beyond the basic nutrition, improve physical, psychological and behavioral performances and have authorized scientific based claims. The action mechanism of prebiotics include selective increase/decrease in specific intestinal bacteria that modulate local cytokine and antibody production, increase in short chain fatty acids production and enhanced binding of these fatty acids to G-coupled protein receptors on leucocytes, interaction with carbohydrate receptors on intestinal epithelium and immune cells, partial absorption resulting in local and systemic contact with immune system 8. The existing prebiotics are classified as emerging prebiotics, established prebiotics, prebiotics with health promoting applications and valuable prebiotics. There are different modes of production for different prebiotics like enzymatic hydrolysis, alkali isomerization and solid liquid extraction. A large number of prebiotic products have been produced by various countries and many of these products have been currently commercialized. However, it is very important to confirm their safety levels by conducting studies on animal models followed by clinical trials on human beings. There are variety of prebiotics in the market including various oligosachharides, inulin, sorbitol, mannitol and oligofructans. The present review aims on classification of prebiotics, their mode of action, production and applications with special emphasis on use of xylitol as prebiotic.

Classification of Prebiotics

The existing prebiotics are classified based on their origin and chemical properties. Stowell 9 classified prebiotics as established prebiotics, emerging prebiotics, prebiotics with health promoting applications and valuable prebiotics. Inulin, fructooligosaccharides (FOS), galactologisaccharides (GOS), lactulose and polydextrose are classified as established prebiotics, however, isomaltoligosaccharides (IMO), xylooligosaccharides (XOS) and lactitol are recognized as emerging prebiotics. Chicory root inulin derived (FOS), wheat bran derived arabinoxylooligosaccharide (AXOS) and xyloologosaccharides (XOS) showed huge applications 10. The health promoting applications of mannitol, maltodextrin, raffinose, lactulose and sorbitol have also been shown by many previous authors 11-12. Another prebiotic i.e. resistant starch rich whole grains are not absorbed in the small intestine of healthy individual and later fermented by natural microflora of colon to produce short chain fatty acids (SCFA) 13. The list of non-digestible prebiotics is given in Table 1.

 Table 1: List of Non Digestible Prebiotics

Inulin Starch rich whole grains
Lactulose Fructoligosaccharide (FOS)
Xylitol Galactooligosaccharide (GOS)
Mannitol Xylooligosaccharide (XOS)
Sorbitol Isomaltooligosaccharide (IMO)
Mannitol Arabinoxylooligosaccharide (AXOS)
Raffinose Mannanoligosaccharide (MOS)
Polydextrose Oligofructans

Mode of Action and Production of Prebiotics

Prebiotics reach the large intestine in intact form and hence modulate the gut microbiota by stimulating indigenous beneficial flora and inhibit the growth of pathogenic organisms. Supplementation of prebiotics in the diet influences volatile fatty acid content(VFA), branched chain proportion, ammonia and lactic acid concentration in the gut 14. They also modulate the immune response, metabolism of xenobiotic enzymes and modify the gene expression in cecum, colon and feces. The nutraceutical and pharmaceutical importance of prebiotics have also been shown in many previous studies by various authors. The anti-tumorigenic effect of arabinoxylan rice bran by enhancing the activity of natural killer cells (NK cells) has been reported by Ghoneum and Abedi 15. MOS prevent the colonization of pathogenic bacteria in the intestinal epithelium by modifying the microbial gut ecosystem 16. The reduction in the incidence of colon carcinogenesis has been reported in rats via induction of apoptosis due to increased production of butyrate from prebiotic resistant starch type-3 Novelose 330 17. The prebiotic effect of blueberry for promoting the growth of beneficial bacteria i.e. Bifidobacterium breve and Lactibacillus rhamnosus and thus improving gut health has been reported by Molan et al. 18. Administration of synbiotics (sorbitol and Pediococcus acidolactici LAB 5) for one month lowers the cholesterol level of Swiss albino mice 11. The administration of prebiotics along with probiotics manipulates the intestinal microflora by accelerating the growth of commensal microorganisms and hence preventing Necrotizing enterocolitis (NEC) 19. The composition of oligosaccharide in human milk is similar to a mixture of prebiotics (short chain GOS, long chain FOS and pectin derived acidic oiligosaccharide), which shows immunopotential effect by promoting T helper cells (TH 1 cells) and regulatory T-cells (Treg) and downregulate IgE-mediated allergic response 20. The addition of FOS and inulin (50:50) in cheese enhances conjugated linoleic acid content during ripening and resulting in better quality product with lower atherogenicity index 21. FOS and GOS stimulate the growth of Bifidobacteria and hence improves gut microbiota 22-23.

Table 2: Modes of Production Of Prebiotics

Prebiotic Mode of Production
Inulin Isolation from chicory root
Lactulose Alkali isomerization of lactose
Pectin Enzymatic hydrolysis of lemon peels
Xylitol Solid-Liquid extraction from Lignocellulosic waste materials
Xylooligosaccharides Enzymatic hydrolysis of xylan
Mannanoligosaccharides Enzymatic hydrolysis of mannose
Galactooligosaccharides Trans galactosylation of lactose with Aspergillus oryzae β-galactosidase
Fructooligosaccharides Partial enzymatic hydrolysis of inulin
Isomaltooligosaccharides Enzymatic hydrolysis of starch/Transglucosylation of maltose
Soyabeanoligosaccharides Extraction from soyabean whey
Oligofructans Microwave hydrolysis of levan from Zymomonas mobilis

 FOS and GOS are classified as GRAS (Generally Recognized as Safe) and commonly used prebiotics to develop foodstuffs 24. The species of Lactobacillus and Bifidobacterium are preferred target organisms for prebiotics. Inulin and trans-oligosaccharised are found in many naturally foods like garlic, onions, leeks, shallots, Asparagus, spinach, chicory, peas, beans, lentils, oats and bananas 2. Xylitol is another emerging prebiotic which is found naturally in many fruits and vegetables like lettuce, cauliflower, yellow plums, strawberry, grapes, banana, meshrooms etc. 25. These prebiotics are produced from different sources through different modes (Table 2).

Applications of Prebiotics

Various food applications of prebiotics include their use in infant formulas 26, cheese 27, fermented milk 28, dairy fruit beverages 29, cereals 30, salad dressing 31, thermo protectant 32, edible coating 33, and custard 34.  Health benefits of prebiotics are given in Table 3 include their role in prevention of diseases like gastroenteritis, inflammatory bowel disease, allergies, cancer risk and cardiovascular disorders 35-39.

Table 3: Health Benefits of Prebiotics

Cancer prevention Bacteriocin production
Cholesterol removal Poultry, fishery, pig and cattle feed
Immumopotentiation Prevention and treatment of allergy
Gut health maintenance Treatment of inflammatory bowel disease
Food additive and starter culture Cardioprotective effects
Bone mineralization Improves renal health
Gastroenteritis prevention Improves gut microbiota

 Xylitol, an Emerging Prebiotic

Xylitol is an emerging prebiotic found naturally in many fruits and vegetables. It has received significant focus by various researchers due to its unique properties, which make this polyol sugar industrially important. This pentose alcoholic sugar is also classified under GRAS (Generally Recognized as Safe) status by FDA (Food and Drug Administration). The sweetening power of this alcoholic sugar, xylitol is similar to sucrose but with low calorie content. This non-digestible pentose sugar passes through upper gastrointestinal tract and reaches the caecum, where it is fermented by inhabitant saccharolytic microorganisms to produce by-products such as short chain fatty acids (acetate, propionate and butyrate), gases (hydrogen, methane and carbon dioxide), organic acids and ethanol. Short chain fatty acids (SCFA) enhance the immune response, regulate gut integrity, maintain cholesterol levels, calcium absorption and reduce the chances of irritable bowel syndrome (IBS) 40. Xylitol promotes the growth of health promoting probiotics like Lactobacilli and Bifidobacteria by altering the colonic microflora 41. It also reduces the chances of intestinal infection by reducing the growth of putrefactive bacteria (Clostridium perfringens) and pathogenic bacteria (Salmonells, Shigella, Listeria, Escherichia coli, Clostridium difficile) through secretion of bifidobacteria bacteriocin like materials against these pathogenic organisms 42-43. Xylitol is also considered as preferable fermentable carbohydrate for several important strains of bacteria, which reduces the growth of opportunistic pathogens (Escherichia coli, Candia albicans) through competition for growth medium and adhesive area. Xylitol reduces the chances of cancer and it also improves the metabolism of glucose, lipid and cholesterol. The inhibitory effect of xylitol on the growth of Candida albicans has been reported by Vargas et al. 44. The fiber like properties of xylitol reduces the excretion of nitrogen and thereby decreases the formation of ammonia and other end products of protein catabolism. These attributes may contribute to reduction in the risk of colon carcinogenesis. It also improves the availability of essential minerals and production of vitamin (B1, B6, B12 and folic acid) 45. The addition of 5% oligosaccharide in the diet of rats enhanced absorption of calcium (15-30%) and magnesium (20-40%) due to lowering of pH and production of short chain fatty acids for enhancing the solubility of minerals 46. Xylitol also reduces the levels of nitrogen excretion, ulcerative colitis, cancer and glucose tolerance. It maintains normal stool consistency and thereby reduces the chances of diarrhea and constipation 47-48.

Along with prebiotic potential, xylitol has many other promising applications in food, pharmaceutical, odontological and medical sectors due to its unique properties like insulin independent metabolism, absence of maillard reaction, negative heat of dissolution, anticariogenic and antiketogenic properties. Very little toxicity has been found with xylitol through various routes of administration. It has shown negative results for tetrogenicity, embryogenicity and reproductive toxicity for mutagenicity and clastogenicity through in vivo and in vitro studies 49-51. GRAS status has been given to this polyol sugar by FDA in 1986 and it is declared as safe for human consumption. The joint FAO/WHO Experts Committee on Food Additives recommended xylitol as safe for human consumption and it is also suggested that there is no requirement of additional toxicological studies for this sugar. The global demand of xylitol is increasing at a very fast rate and its market is expected to be USD 15.4 billion by 2021 52. The current conventional costlier chemical methods are unable to fulfill the needs. Therefore, biotechnological methods should be adapted by utilization of agrowaste materials through utilization of microbial cells and enzymes using purified xylose reductase to reduce the cost of this industrially important polyol sugar. Further, modern technologies like in silico characterization of enzyme, recombinant DNA technology should also be adapted to enhance the yield and to fulfill industrial demand of xylitol.

CONCLUSION AND FUTURE PROSPECTS

 The present study concludes the beneficial health effects of prebiotics through various modes of action. In the past, extensive research has been conducted on prebiotics and many prebiotic products have already be used commercially in different countries of the world. The species of Lactobacillus and Bifidobacterium are the main target for prebiotics. Stability, safety and resistance to digestion are the main criteria for an efficient prebiotic. Hence, xylitol is emerging as a good prebiotic due to its unique properties and health benefits. The previous clinical studies on xylitol already proves its safety concerns. However, its commercial production is limited due to high cost, which limits its use for industrial purpose. Therefore, there is an urgent need to explore new methods for the production of this naturally occurring polyol prebiotic which can lower its production cost. New fermentation methods involving recombinant microorganisms and enzymes should also be used to increase the product yield. The combination of prebiotics along with omics studies (genomics, metabolomics) and system biology will further help to understand the relationship between gut microbiota, health status and effect of drugs and antibiotics in the individual. Thereafter, in silico computational tools and softwares should also be used to understand their anti-inflamatory effects, mode of action and risks.

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