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Keywords:

  • colon microbiota;
  • functional food;
  • oligosaccharides;
  • prebiotics;
  • probiotics

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Production, Purification, and Structural Characterization
  5. Latest Validated Benefits
  6. Future Directions
  7. Conclusions
  8. Acknowledgments
  9. References

Functional oligosaccharides have emerged as valuable components of food and dietary supplements. Their resistance to digestion and fermentation by colonic microbes has given them the nutritional edge. Apart from implications as dietary fibers, sweeteners, and humectants, they are hailed as prebiotics. Their beneficial effects extend from antioxidant, anti-inflammatory, immunomodulatory, antiallergic, hypotensive, hyperlipemic, neuroprotective to anticancer. The rising popularity of bioactive oligosaccharides has accelerated the search for their generation from new, sustainable sources. The surfacing crucial role in healthcare and unprecedented demand necessitates deeper investigation. The present review embodies an overview on various aspects of production, properties with emphasis on therapeutic applications of functional oligosaccharides. The biological efficacy and possible mechanisms of action of oligosaccharides have also been discussed.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Production, Purification, and Structural Characterization
  5. Latest Validated Benefits
  6. Future Directions
  7. Conclusions
  8. Acknowledgments
  9. References

Oligosaccharides are low molecular weight carbohydrates, containing sugar moieties with degree of polymerization (DP) between 3 and 10. The nondigestible oligosaccharides are resistant to human digestive enzymes viz., salivary and pancreatic amylases (Weijers and others 2008). Thus, they pass through the upper digestive system intact and get fermented in the lower colon, producing short-chain fatty acids (SCFAs), which, in turn, nourish the resident beneficial microbiota (Mussatto and Mancilha 2007; Morris and Morris 2012). Most of the prebiotics identified till date are nondigestible oligosaccharides (Wang 2009; Saad and others 2013). Since their recognition as important food additives in 1980s, these functional oligosaccharides have gained phenomenal popularity (Saad and others 2013). Their health benefits graduated them to nutraceutical league with ever increasing market share. The U.S. market for prebiotic ingredients is currently estimated at metric tons and million dollars, which is predicted to double in the next 5 y to more than U.S. $220 million, according to market researcher Frost and Sullivan. The Transparency Market Research observes that the prebiotics demand was worth USD 2.3 billion in 2012 and is expected to reach U.S. $4.5 billion by 2018. The stability of oligosaccharides depends on the sugar residue content, anomeric configuration, and linkage types (Raman and others 2005). The functional oligosaccharides include lactulose, fructo-oligosaccharides (FOSs), galacto-oligosaccharides (GOSs), soybean oligosaccharides (SOs), lactosucrose, isomalto-oligosaccharides (IMOs), gluco-oligosaccharides (GLOSs), xylo-oligosaccharides (XOSs), gentio-oligosaccharides (GeOSs) arabinoxylan oligosaccharide (AXOS), mannan oligosaccharides (MOSs), pectin-derived acidic oligosaccharides (pAOSs), chito-oligosaccharide (COS), agaro-oligosaccharide (AOS), human milk oligosaccharide (HMO), cyclodextrins (Patel and Goyal 2011), xanthan-derived oligosaccharides (XDOs) (Wu and others 2013a), and alginate-derived oligosaccharide (ADO) (He and others 2013). Oligosaccharide research is an area of intense investigation, for its multitude of biological potencies. Several reviews have been published in recent times, but they are not holistic, rather they deal with individual oligosaccharides. Sangwan and others (2011) summarized the role of GOS; Costa and others (2012) demonstrated that the importance of FOS and Bertino and others (2012) have reviewed the biological functions of HMO. Raman and others (2013) elaborated the significance of tailor-made prebiotics, probiotics, and synbiotics in colorectal cancer management owing to their antimutagenic activity. On the other hand, this manuscript deals with most of the existing functional oligosaccharides, and their food and pharmaceutical applications. The authors had published a review article on “functional oligosaccharides” in a reputed journal in 2011 (Patel and Goyal 2011). Since then, several key developments have occurred in this area. This manuscript furnishes an account of those key findings. Therefore, an attempt has been made in the following text to dovetail the enormous information available on the various aspects of oligosaccharides as prebiotics.

Production, Purification, and Structural Characterization

  1. Top of page
  2. Abstract
  3. Introduction
  4. Production, Purification, and Structural Characterization
  5. Latest Validated Benefits
  6. Future Directions
  7. Conclusions
  8. Acknowledgments
  9. References

Oligosaccharides can be obtained from natural sources and can also be synthesized (Courtois 2009). Various natural sources of oligosaccharides are milk, honey, sugarcane juice, rye, barley, wheat, soybean, lentils, mustard, fruits, and vegetables such as onion, asparagus, sugar beet, artichoke, chicory, leek, garlic, banana, yacon, tomato, and bamboo shoots. The common manufacturing methods are hydrolysis of polysaccharides, chemical, and enzymatic polymerization from disaccharide substrates (Mussatto and Mancilha 2007). Acid, alkali, and enzymatic hydrolysis of polysaccharides generates oligosaccharides of desired structure and functional properties. In general, enzymatic methods are preferred for oligosaccharide synthesis due to their high selectivity and yields (Moracci and others 2001; Saad and others 2013), and environmental-friendly nature (Hongzhi and Zuyi 2002). Radiolysis has been found effective in few instances (Jalan and others 2013). Recombination and immobilization technology have also been employed for oligosaccharide production (Kothari and others 2012; Wu and others 2013a). Delattre and Vijayalakshmi (2009) have reviewed a host of methods for preparation of bioactive oligosaccharides. Enzymatic reactor with monolith technology (macroporous matrices) for immobilization of glycosyltransferases has been suggested promising for the automated and efficient synthesis of oligosaccharides. The acidic oligosaccharides from various plant pectins were produced by treatment with mixtures of protease and cellulose (Zykwinska and others 2008). Enzymatic degradation (mostly by glucuronan lyases) of polyglucuronic acid (β-(1, 4)-linked glucuronic acid) and subsequent generation of acidic oligosaccharides (oligoglucuronans) with biological activities has been reviewed by Elboutachfaiti and others (2011). Acidic oligosaccharides were also generated from apple pectin by dynamic high-pressure microfluidization (Chen and others 2013). Fang and others (2012) derived feruloylated oligosaccharides by hydrolysis of arabinoxylans in cereal bran. Jian and others (2013) conducted enzymatic hydrolysis of Gleditsia sinensis (a locust tree) gum to obtain MOS. Using response surface methodology, they determined the optimum hydrolysis conditions to be 8.1 U/g enzyme loading, 57.4 °C temperature, and 34.1 h reaction time. Yamada and others (2013) conducted hydrolytic depolymerization of chondroitin sulfate and obtained oligosaccharides containing N-acetyl-D-galactosamine residue at their reducing ends. de Araujo and others (2013) produced functional COS using chitosanases from Paenibacillus chitinolyticus and Paenibacillus ehimensis. Maximum conversion of 99.2% was achieved after 12 h incubation of chitosan with enzymes produced by P. ehimensis. Xiao and others (2013) obtained XOS by hydrolyzing bamboo culm. They achieved maximum yield of 47.49% at 180 °C after 30 min. Majumder and others (2009) subjected glucan elaborated by Leuconostoc mesenteroides NRRL B-742 to microwave-assisted acid hydrolysis for the production of GLOS. A reaction time of 2 min resulted in 2.5% yield of GLOS. Wang and Lu (2013) investigated the production of XOS by microwave-assisted enzymatic hydrolysis of wheat bran and obtained 3.2 g dry XOS from 50 g dry bran powder. Jalan and others (2013) generated 63.0% FOS from 250 kGy γ-irradiated 10% levan from Bacillus megaterium. Wu and others (2013b) expressed mutated recombinant β-galactosidase from Sulfolobus solfataricus P2 in Escherichia coli BL21 (DE3) and obtained GOS. Diez-Municio and others (2013) produced FOS by using inulosucrase from Lactobacillus gasseri DSM 20604. Kothari and others (2012) used sodium-alginate-immobilized glucansucrase from L. mesenteroides in the acceptor reaction with maltose to produce GLOS.

Purification of oligosaccharide to homogeneity is an indispensable step. Several methods like use of high-shear rotating disk filtration module (Mellal and others 2008), ion exchange resins (Hernandez and others 2009), size exclusion chromatography (SEC) (Ballance and others 2009), activated charcoal (Nobre and others 2012), immobilized yeast cells (Lu and others 2013), ultrafiltration, and nanofiltration (Akin and others 2012) have been employed to purify oligosaccharides from sugar mixtures. The purified and homogenized oligosaccharides are subjected to structural elucidation based on tools like high-performance anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD) (Ammeraal and others 1991), gas chromatography (GC) with flame ionization detection (FID) (Low 1996), high-performance liquid chromatography (HPLC) with evaporative light scattering detection (ELSD) or refractive index (RI) detection (Hernandez and others 1998), fluorophore-assisted carbohydrate electrophoresis (FACE) (O'Shea and others 1998), thin layer chromatography (TLC) (Reiffova and Nemcova 2006), capillary electrophoresis with a UV-diode array detector (Wahlstrom and others 2013), electrospray ionization mass spectrometry (ESI-MS), nuclear magnetic resonance (NMR) and Fourier transform infrared (FTIR) spectroscopy, and X-ray diffraction (Zhao and others 2013). The schematic illustration of the oligosaccharide research for prebiotics has been presented in Figure 1.

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Figure 1. A general strategy for the prebiotic oligosaccharide research.

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Latest Validated Benefits

  1. Top of page
  2. Abstract
  3. Introduction
  4. Production, Purification, and Structural Characterization
  5. Latest Validated Benefits
  6. Future Directions
  7. Conclusions
  8. Acknowledgments
  9. References

The benefits of consuming foods containing prebiotic oligosaccharides have been demonstrated by a number of in vitro and in vivo (animal and human) studies. The majority of the effects claimed by the prebiotics are associated with optimized colonic function and metabolism (Saad and others 2013), as shown in Figure 2. Among the numerous benefits conferred by the oligosaccharides, only a few recently validated ones are summarized here.

image

Figure 2. Health benefits of prebiotic oligosaccharides.

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Gut health restoration and probiotics induction

Enteritis, inflammatory bowel disease, and constipation are gut-associated ailments, which respond well to oligosaccharides. The oligosaccharides have often proved suitable substitute to antibiotics. In an in vitro study, pAOS at a dose of 2.5 mg/mL was shown to inhibit the adherence and invasion of Caco-2 cells by Campylobacter jejuni (Ganan and others 2010). Yen and others (2011) conducted a placebocontrolled, diet-controlled trial to determine the effect of IMO supplementation on fecal microflora and bowel function in constipated elderly subjects after 8 wk ingestion. They observed that the bifidobacteria, lactobacilli, and bacteroides counts significantly increased and clostridia count decreased. Daily fecal excretion of acetate and propionate, the frequency of spontaneous defecation and wet fecal mass were increased. They also found that plasma total low-density lipoprotein and cholesterol levels were lower. The IMO supplementation of a low-fiber diet improved colonic microflora pattern and bowel movement in a time-dependent fashion. Manisseri and Gudipati (2012) reported an in vitro prebiotic action of ragi bran-derived crude XOS on Bifidobacterium and Lactobacillus sp. Zhou and others (2012) determined the fermentation characteristics of soybean meal oligosaccharide through an in vitro system. Incubation of colon-derived digesta with this oligosaccharide increased the microbial diversity and population of bifidobacteria and lactobacilli, while decreasing the escherichia and streptococci counts. Feasibility of employment of this oligosaccharide for gut microbiota balance in colon and metabolism modulation came forth. Higashimura and others (2012) investigated the therapeutic effect of AOS on intestinal inflammation in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model of mice. The oligosaccharide administration induced hemeoxygenase-1 (HO-1) expression in colonic mucosa. The induction was observed mainly in F4/80 positive macrophages. Increased colonic damage and myeloperoxidase activity induced by TNBS treatment were inhibited by the AOS administration. In RAW264 cells (mouse leukemic monocyte-macrophage), AOS enhanced HO-1 expression in time- and concentration-dependent manner, suppressing lipopolysaccharide (LPS)–induced tumor necrosis factor-alpha (TNF-α) expression. Garcia-Peris and others (2012) conducted a randomized double-blind, placebocontrolled study to find the effect of prebiotic mixture on depleted lactobacilli and bifidobacteria post radiotherapy. A mixture of fiber (inulin and FOS, 1 : 1) was administered twice a day from 1 wk before to 3 wk after irradiation regime. Cultural analysis revealed significant increase in probiotic count, 3 wk after the fiber intake. Functional oligosaccharides exert synergistic effect along with probiotic strains of lactic acid bacteria. Chaluvadi and others (2012) reported higher levels of Bifidobacterium breve, Lactobacillus acidophilus, and Lactobacillus reuteri from the synbiotic matrices supplemented with FOS, inulin, and pAOS compared to alginate alone. These results suggested that synbiotics protected probiotic bacteria and extended their shelf-life under refrigerated aerobic conditions. Coencapsulation of L. acidophilus in an alginate-xanthan mixture with inulin was also reported to increase the effectiveness of functional foods (Nazzaro and others 2009). Peng and others (2013) inferred from a 4-wk feeding in vivo study on mice that FOS was an important component in the mixture of dietary fiber both in maintaining the balance of gut microbiota and production of SCFAs. Hansen and others (2013) fed 10% (w/v) XOS-supplemented diet to mice for 10 wk from weaning. The diet significantly increased bifidobacterium colonies throughout the intestine. Increased production of SCFAs in the gut occurred which resulted in downregulation of low-grade inflammatory cytokines (interleukin 1β [IL-1β] and interferon γ [IFN-γ]). Chen and others reported that acidic oligosaccharides from apple pectin increased the number of bifidobacteria and lactobacilli, and produced a higher concentration of acetic, lactic, and propionic acid in vitro. This was associated with decrease in the number of bacteroides and clostridia. D-lactic acidosis (also referred to as D-lactate encephalopathy) is a syndrome affecting individuals with short bowel syndrome or following jejuno-ileal bypass surgery. Intake of high-carbohydrate foods leads to elevation of plasma D-lactate concentration, manifests into neurologic symptoms like altered mental status, slurred speech, and loss of physical coordination. Takahashi and others (2013) studied the therapeutic effect of synbiotic (B. breve Yakult and Lactobacillus casei Shirota as probiotics + GOS as a prebiotic) treatment in a patient with recurrent D-lactic acidosis. They recorded reduction in the serum D-lactate levels and the patient did not have the recurrence for 3 y even without dietary restriction. Synbiotics attenuated the colonic absorption of D-lactate by prevention of causative bacterial proliferation as well as stimulation of intestinal motility.

Immunomodulation

The immunomodulatory effects of oligosaccharides have gained significant credence. Delgado and others (2012) studied the in vivo effects of FOS-rich yacon tuber intake on the immune system of mice for 30 consecutive days. Results showed that daily consumption of yacon did not exert a negative effect on the immune system, rather helped to retain an anti-inflammatory state in phagocytic cells, and improved mucosal immunity, possibly by annulling the risks associated with autoimmune and metabolic diseases. Jiao and others (2012) investigated the activation effect of oligosaccharide extract from the roots of Panax ginseng on murine peritoneal macrophages. Immunological tests showed that the treatment significantly increased phagocytosis of macrophages and promoted the production of nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), and reactive oxygen species (ROS). Dose-dependent stimulation of NO formation through the upregulation of inducible nitric oxide synthase (iNOS) activity was also observed. Fang and others (2012) elucidated in vitro immunomodulatory effects of feruloylated oligosaccharides through the variations of proinflammatory mediators. It induced TNF-α, IL-1β, IL-6, NO, and prostaglandin E2 (PGE2) production in unstimulated as well as LPS stimulated RAW264.7 cells (mouse leukemic monocyte macrophage) (Figure 3). PGE2 production was significantly suppressed at an oligosaccharide level of 100 μg/mL. Lane and others (2013) investigated immunomodulatory role of bovine colostrum in an in vitro study in colonic epithelial cells (HT-29) and reported that the milk oligosaccharide contributed to the intestinal immune response.

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Figure 3. Schematic representation of oligosaccharide induced anti-inflammatory effect (Higashimura and others 2012).

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Cancer prevention

Despite impressive developments in chemotherapy, the existing drugs fall short of eradicating cancer. Oligosaccharides are being probed for their anticancer potential eradication. Munjal and others (2012) investigated if the expression of genes related to biotransformation is modulated by fermented dietary fibers. They found that the fermentation supernatant of inulin incubated with oligofructose resulted in a significant increase in glutathione S-transferase A4 (GSTA4) mRNA expression enhanced catalase activity and reduction in the amount of H2O2-induced DNA damage in human colonic carcinoma HT29 cells. This finding endorses the role of dietary fibers in primary chemoprevention. Gao and others (2012) investigated the in vitro effect and mechanism of inhibition and apoptosis of human ovarian cancer SKOV-3 cells by COS and reported efficient inhibition of cell proliferation and apoptosis induction in a dose-dependent manner. Enoki and others (2012) observed that AOS feeding led to delayed appearance and decreased number of tumors in 2-stage mouse skin carcinogenesis model. The production of PGE2 (a key player in carcinogenesis) was suppressed by AOS intake in 12-O-tetradecanoylphorbol-13-acetate (TPA) induced ear edema model. Also, cyclooxygenase-2 and microsomal PGE synthase-1, the rate-limiting enzymes in PGE2 production in human monocytes, were downregulated by the oligosaccharide. Kim and others (2012a) investigated anticancer properties of hetero-chito-oligosaccharides (derived from chitosans with various degree of deacetylation) on human promyelocytic HL-60 cells using flow cytometry and morphological analysis. The results indicated that 90-COS III (with a relatively higher degree of deacetylation and lower molecular weight) possessed the highest anticancer activity. Fernandes and others (2012) evaluated the efficacy of COS (in orange juice) in N-butyl-N-(4-hydroxybutyl) nitrosamine-induced rat bladder cancer chemoprevention and therapy. Results revealed preventive effect on bladder cancer development and a curative effect on established bladder tumors, regulated by the concentration of COS ingested. Lower doses of COS (50 and 250 mg/kg) had only therapeutic effects. Li and others (2013) studied the effect of apple-derived acidic oligosaccharides on the cellular viability of human colon carcinoma HT29 cells and underlying mechanism and reported that it decreased the cellular viability in dose-dependent manner. Enhanced expression of Bax and decreased levels of Bcl-2 and Bcl-xl was measured. It induced cell cycle arrest in S phase, which was correlated with the decreased expression of Cdk 2 and cyclin B1. In a comparative in vivo study, inulin was reported to be a better prebiotic than lactulose in reducing the initiation of colon cancer in male Sprague Dawley (SD) rats. The proposed protection against cancer may be either due to better ability of inulin to reach distal colon, bifidogenic property, or ability to reduce the activity of bacterial enzymes (β-glucuronidase and β-glucosidase) (Verma and Shukla 2013).

Antihypertensive effects

A growing body of evidences suggests that oligosaccharides from various sources can lower high blood pressure. Ueno and others (2012) investigated the effects of sodium alginate oligosaccharide on the development of spontaneous hypertension in rats, in an in vivo study. Treatment with the oligosaccharide for 7 wk significantly attenuated the systolic blood pressure in spontaneous hypertensive rats (SHRs). Also, the morphologic glomerular damage was lowered reducing the early-stage kidney injury risk. Moriya and others (2013) investigated the mechanism of the antihypertensive effect of sodium alginate oligosaccharide using another model of hypertensive rats, Dahl salt-sensitive rats. The rats fed with high-salt (4% NaCl) diet were subcutaneously administered with the oligosaccharide at 60 mg/d for 14 d. The systolic blood pressure as quantified by tail cutoff method was decreased. Also, the level of urinary protein excretion was lower in the treated rats. Dahl salt-sensitive rats showed suppression of elevation in blood pressure in vivo by MOS (Hoshino-Takao and others 2008).

Hepatic protection

Convincing numbers of findings supporting the liver protective potential of oligosaccharides have accumulated in recent times. Malaguarnera and others (2010) conducted a double-blind, randomized study to investigate the effect of a blend of bifidobacteria and FOS in ameliorating hepatic encephalopathy (a reversible neuropsychiatric syndrome) in cirrhosis patients. After 30 and 60 d, the patients treated with the symbiotic mix had lower blood ammonia levels and showed improvement in psychometric tests. Chronic subcutaneous administration of D-galactose induced oxidative stress. Chen and others (2011) determined if FOS attenuated oxidative stress and hepatopathy in Balb/c mice. When administered along with D-galactose at a dose of 5% for 52 d, the oligosaccharide restored the normal level of hepatic superoxide dismutase (SOD), glutathione peroxidase (GPx), triacylglycerols, and plasma alanine aminotransferase (ALT) levels. Pachikian and others (2013) reported that fermentable dietary FOS could also control hepatic steatosis induced by omega-3 fatty acids (ω-3 PUFA) exhaustion. Mice fed a ω-3 PUFA-depleted diet for 3 mo were given with FOS during the last 10 d of treatment. These mice exhibited higher cecal bifidobacterium and lower roseburia population (Firmicute belonging to the Clostridium coccoides cluster). Microarray analysis of hepatic mRNA revealed that FOS supplementation reduced hepatic triglyceride accumulation through a proliferator-activated receptor α-stimulation of fatty acid oxidation and lessened cholesterol accumulation by inhibiting sterol regulatory element binding protein 2-dependent cholesterol synthesis. Tissue analysis confirmed the inhibition of fatty acid oxidation.

Allergic inflammation mitigation

Both animal studies and human clinical trials showed that dietary intervention with several oligosaccharides such as HMO, GOS, FOS, and pAOS in early life could lead to the prevention of allergic reactions (Jeurink and others 2013). Yasuda and others (2012) checked the preventive and therapeutic effects of dietary supplementation with FOS in an in vivo study in murine model of allergic peritonitis. Test mice were fed a FOS fortified diet (0% or 2.5%) ad libitum and killed on the 43rd day. Results of parameter analysis showed that FOS alleviated the peritoneal inflammation characterized by trafficking of eosinophils and neutrophils in the peritoneal cavity. Also, it significantly suppressed the levels of IL-5 and eotaxin in the peritoneal lavage fluid. Further, the supplemented diet significantly reduced the serum allergen-specific IgG1 level, while increasing the total immunoglobulin A (IgA) levels in the cecal contents. Arslanoglu and others (2012) conducted a double blind, placebo-controlled study to investigate the protective effect of a mixture of oligosaccharides on atopic dermatitis. A significant reduction in 5 y cumulative incidence of any allergic manifestation was observed lower in the short-chain GOS and long-chain FOS group. Children fed with food supplemented with this oligosaccharide mix were less prone to allergic rhinoconjunctivitis (runny nose and inflammation of conjunctiva) and urticaria (hives). This oligosaccharide blend, when started early in life conferred a protective effect against allergic manifestations in high-risk infants and the protection lasted beyond infancy up to 5 y. Weise and others (2013) observed that dietary arachidonic acid/docosahexaenoic acid and GOS/polydextrose significantly ameliorated the severity of ovalbumin-induced dermatitis in an in vivo study in mice. Lowered lesional CD8(+) and mast cells were most pronounced in the combinatory-treatment group. Moreover, in GOS/polydextrose treated mice, IFN-γ and transforming growth factor beta (TGFβ) expression was increased in skin lesions. This supplementation might be beneficial in the dietary management of human atopic eczema.

Oxidative stress lowering and neuroprotection

Oxidative stress triggers neurodegenerative disorders and oligosaccharides have a repressive effect on these degenerative actions. Wang and others (2007) investigated in vitro potential of acidic oligosaccharide sugar chain, derived from brown alga Echlonia kurome Okam, on β-amyloid plaques-induced inflammatory response and cytotoxicity. The oligosaccharide inhibited the reactive phenotype of astrocytes (those surround the β-amyloid plaques), blocked cellular oxidative stress, reduced the production of TNF-α and IL-6, and prevented the influx of Ca2+. Tusi and others (2011) studied the effects of alginate oligosaccharide on rat adrenal pheochromocytoma PC12 cells and Aß-injected rats. The oligosaccharide treatment protected against endoplasmic reticulum and mitochondrial-dependent apoptotic cell death and protected the hippocampus from Alzheimer's disease. In both in vitro and in vivo tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), AOS promoted Bcl-2 expression while preventing Bax expression, and inhibited caspase-3 activation. N-acetyl chito-oligosaccharides have also been reported to exhibit an inhibitory effect against DNA and protein oxidation with increased intracellular glutathione (GSH) level and direct intracellular radical scavenging effect in mouse macrophages (RAW 264.7) (Ngo and others 2009). Hsia and others (2012) explored the effects of FOS on subcutaneous D-galactose induced oxidative damage of lipids, proteins, and mitochondrial DNA and erythrocyte antioxidant enzyme activities in mice. Oligosaccharide supplementation normalized the abnormal rise in the malonaldehyde dimethyl acetal (MDA) level in the plasma, liver and cerebral cortex and protein carbonyl levels in liver and hippocampus. Attenuation of the oxidative stress was attributed to the prebiotic effect of FOS, generating fermentation products. Potential therapeutic implications of oligosaccharides in treatment of neurodegenerative diseases like Alzheimer's certainly deserve further assessment.

Dermal safety

Oligosaccharides are appreciated for improvement of the skin barrier function and hydration. The mechanism is governed by amelioration of keratinocytes resulting in homeostasis and skin regeneration. Kim and others (2012b) studied the effect of a 3 to 5 kDa COS on establishing equilibrium between the expression of collagen degrading matrix metalloproteinases (MMPs) and collagen synthesis using ultraviolet light on dermal fibroblasts. The oligosaccharide inhibited collagenase and gelatinase MMP expression by promoting the expression of their inhibitors. Further, it enhanced collagen synthetic markers procollagen, type I, III, and IV collagens. Miyazaki and others (2013) conducted a double-blind, placebo-controlled trial on healthy women and found that daily intake of fermented milk containing the probiotic B. breve strain Yakult and GOS reduced serum total phenol levels, preventing skin dryness. Dermal protection was correlated to a decrease in phenol production by gut microbiota.

Moreover, some of the recent relevant clinical trials of different oligosaccharides on the different clinical issues have been summarized in Table 1.

Table 1. Relevant human clinical trials of some potential prebiotic oligosaccharides
OligosaccharidesDose and durationHealth benefitsReferences
FOS15 g/d for 4 wkIncrease fecal bifidobacteria, induce immunoregulatory dendritic cell (DC) responses and reduce Crohn's disease activity.Benjamin and others (2011)
Synbiotic containing FOS200 mL/d synbiotic shake with 2 g FOS for 30 d.Significant increase in high-density lipoprotein (HDL) and a significant decrease of glycemia in elderly people aged 50 to 60 yMoroti and others (2012)
GOS2·5 or 5 g for 3-wk periods in a random orderIncrease calcium absorption and gut bifidobacteriaWhisner and others (2013)
XOS4 g/d (n = 12) or a placebo (n = 14) for 8 wkEffective in improving the blood sugar and lipids in type 2 diabetesSheu and others (2008)
COS500 mg twice daily before meal for 6 wkDecreases plasma lipid levels in healthy menChoi and others (2012)
IMO mixture and its hydrogenated derivative (IMO-H)3 to 4 g/dLow acidogenicity in oral cavityKaneko and others (1995)
IMO15g/d for 7 dImprove the intestinal flora in human intestineGu and others (2003)
AXOSApproximately 2.14 g/d for 3 wkAlter gastrointestinal fermentation characteristics with higher SCFA concentrationsDamen and others (2012)

Future Directions

  1. Top of page
  2. Abstract
  3. Introduction
  4. Production, Purification, and Structural Characterization
  5. Latest Validated Benefits
  6. Future Directions
  7. Conclusions
  8. Acknowledgments
  9. References

Oligosaccharide research has become a major area of food and nutraceutical research and development. Efforts are continuously being made to use them as a cure for various human ailments like obesity, diabetes, and cancer. The hunt for new, novel sources of oligosaccharides seems to be an interesting quest. A plethora of natural and industrial by-products are available, which need to be explored as potential sources of functional oligosaccharides. Marine algae, mushrooms, wild tubers, and crop wastes, seem to hold enormous prospect. Patel (2012) reviewed the physiological importance of cereal brans and projected them as a promising source of nondigestible oligosaccharides viz., XOS and AXOS. Batra and others (2013) identified oligosaccharide to be an active component of medicinal mushroom Ganoderma lucidum (Lingzhi or Reishi). HMO is increasingly being validated for their prebiotic and anti-infective activities. Taking cue from it, milk from bovine and other farm animals is being studied for the possibility of harvesting oligosaccharides with biological properties similar to human milk (Urashima and others 2013). Chemical modifications, such as sulfation, acylation, and epimerization, are expected to result in oligosaccharides with better specificity. Sulfated κ-carrageenan oligosaccharides from red alga Kappaphycus striatum showed superior antitumor and immunomodulatory activity than their unmodified forms (Yuan and others 2011). Zhao and others (2013) subjected COS to acylation and found the N-furoyl COS to possess better hydroxyl radical scavenging activity than the unsubstituted form. Tailor-made oligosaccharides with envisaged functional attributes remain the ultimate challenge, requiring interdisciplinary endeavor.

Conclusions

  1. Top of page
  2. Abstract
  3. Introduction
  4. Production, Purification, and Structural Characterization
  5. Latest Validated Benefits
  6. Future Directions
  7. Conclusions
  8. Acknowledgments
  9. References

Nondigestible, low glycaemic oligosaccharides possess a plethora of health benefits. Their incorporation into the regular diet has been an effective remedy for gastric complications, cancer, obesity, allergic inflammation, immune deficiency, and myriad other health problems. Elucidation of the tolerability and effectiveness of the oligosaccharides from various sources for the enrichment of intestinal microflora toward beneficial populations is a thrust area of research. Low cost can make it affordable to the mass consumers, for which cheap sources and large-scale production technology will be required. An array of sustainable resources with promising oligosaccharide cache exists for possible exploitation. In a nutshell, this review reflects on the above-mentioned facets, providing a vision for future research paths. It is expected to be a catalyst in adoption of oligosaccharide-based nutraceuticals.

Acknowledgments

  1. Top of page
  2. Abstract
  3. Introduction
  4. Production, Purification, and Structural Characterization
  5. Latest Validated Benefits
  6. Future Directions
  7. Conclusions
  8. Acknowledgments
  9. References

The authors would like to thank Dept. of Biotechnology, Government of India, for the financial support. The authors have no conflict of interests.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Production, Purification, and Structural Characterization
  5. Latest Validated Benefits
  6. Future Directions
  7. Conclusions
  8. Acknowledgments
  9. References
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