The Scientific World Journal

The Scientific World Journal / 2015 / Article

Review Article | Open Access

Volume 2015 |Article ID 289267 | 15 pages | https://doi.org/10.1155/2015/289267

Implication of Fructans in Health: Immunomodulatory and Antioxidant Mechanisms

Academic Editor: Aida Turrini
Received23 Oct 2014
Revised29 Jan 2015
Accepted06 Mar 2015
Published19 Apr 2015

Abstract

Previous studies have shown that fructans, a soluble dietary fiber, are beneficial to human health and offer a promising approach for the treatment of some diseases. Fructans are nonreducing carbohydrates composed of fructosyl units and terminated by a single glucose molecule. These carbohydrates may be straight or branched with varying degrees of polymerization. Additionally, fructans are resistant to hydrolysis by human digestive enzymes but can be fermented by the colonic microbiota to produce short chain fatty acids (SCFAs), metabolic by-products that possess immunomodulatory activity. The indirect role of fructans in stimulating probiotic growth is one of the mechanisms through which fructans exert their prebiotic activity and improve health or ameliorate disease. However, a more direct mechanism for fructan activity has recently been suggested; fructans may interact with immune cells in the intestinal lumen to modulate immune responses in the body. Fructans are currently being studied for their potential as “ROS scavengers” that benefit intestinal epithelial cells by improving their redox environment. In this review, we discuss recent advances in our understanding of fructans interaction with the intestinal immune system, the gut microbiota, and other components of the intestinal lumen to provide an overview of the mechanisms underlying the effects of fructans on health and disease.

1. Introduction

Fructans are recognized as health-promoting food ingredients. They are found in a small number of mono- and dicotyledonous families of plants, such as Liliaceae, Amaryllidaceae, Gramineae, Compositae, Nolinaceae, and Agavaceae. Various fructan-containing plant species, including asparagus, garlic, leek, onion, Jerusalem artichoke, and chicory roots, are often eaten as vegetables [13]. Substantial variation in chemical and structural conformations makes fructans a flexible and appealing ingredient for different dietary products such as nutraceuticals.

Inulin-type fructans (ITFs) are among the most studied; ITFs are indigestible, fully soluble, fermentable food ingredients with known prebiotic properties. ITFs are linear fructose polymers with β(2→1) linkages found naturally in chicory roots, wheat, onion, garlic, and other foods. In the scientific literature, ITFs are frequently referenced generically but inconsistently as “inulin,” “oligofructose” (OF), and “fructooligosaccharides” (FOS) [4]. Agave fructans have a more complex, highly branched structure, including β(2→1) and β(2→6) linkages. Thus, Agave fructans can contain an external glucose, characteristic of graminans, and an internal glucose, characteristic of neofructans. For this reason, this type of fructans has been called “agavins” [5].

Fructans contribute to host health through multiple mechanisms. Fructans are selective substrates for probiotic bacteria stimulating probiotic bacterial growth, which can confer health benefits to the host through the several mechanisms, including immunomodulation [68]. Fructans may also act as scavengers of reactive oxygen species [9], decreasing inflammation and improving redox status. Fructans are fermented to short chain fatty acids (SCFAs), which have important implications in host health. In addition, direct interaction between fructans and intestinal immune cells has recently been suggested. The aim of this review is to summarize the latest findings on studies investigating fructans as prebiotics and to provide an overall image of the mechanisms underlying the health effects of fructans.

2. Fructans: Structure, Source, and Synthesis

Approximately 15% of flowering plants store fructans as reserve carbohydrates [10]. Worldwide, the most studied and marketed fructan is inulin, which is obtained primarily from chicory roots. However, some candidate fructans, such as galactooligosaccharides (GOS) derived from lactose and lactulose, have also demonstrated potential prebiotic effects [11]. In addition to chicory root, another potential fructan source includes the more recently investigated Agave fructans. The Agave tequilana Weber azul variety is an economically important species of Agave cultivated in Mexico. Because of its high inulin concentration, this variety is the only species in the Agavaceae family that is appropriate for tequila production. The high inulin concentrations, specifically in the head (pine), provide added economic and environmental value to this species of Agave [12].

Fructans have been classified into 4 groups based on their structural bonds: inulin, levans, graminans, and neoseries fructans (inulin neoseries and levan neoseries mixture) [13]. Inulin is the simplest linear fructan, consisting of β(2→1)-linked fructose residues. Inulin is usually found in plants such as Cichorium intybus (15–20% fructans), Jerusalem artichoke (15–20% fructans), Helianthus tuberosus (15–20% fructans), and Dahlia variabilis (15–20% fructans) (Figure 1) [1315]. Levan-type fructans (also called phleins in plants) can be found in grasses (Poaceae). Levan fructans contain a linear β(2→6)-linked fructose polymer and are found in big bluegrass (Poa secunda) [16, 17]. Graminan-type fructans consist of β(2→6)-linked fructose residues with β(2→1) branches or can consist of more complex structures in which neosugars are combined with branched fructan chains. These complex fructans are usually found in plants such as Avena sativa, Lolium sp., and Agave sp. (15–22% fructans) (Figure 1) [5, 1820]. The inulin neoseries are linear (2-1)-linked β-d-fructosyl units linked to both C1 and C6 on the glucose moiety of the sucrose (Suc) molecule. This results in a fructan polymer with a fructose chain ((mF2-1F2-6G1-2F1-2Fn); F (fructose), G (glucose)) on both ends of the glucose molecule. These fructans are found in plants belonging to the Liliaceae family (e.g., onion and asparagus (10–15% fructans)) [15, 21]. The smallest inulin neoseries molecule is called neokestose. The levan neoseries consists of polymers with predominantly β(2→6)-linked fructosyl residues on either end of the glucose moiety of the sucrose molecule. These fructans are rare, although they have been found in a few plant species belonging to the Poales (e.g., oat) [18].

The length of fructosyl chains varies greatly in plants; plant fructosyl chains are much shorter than those of bacterial fructans. In general, the chain length or degree of polymerization (DP) is between 30 and 50 fructosyl residues in plants but can occasionally exceed 200 [13]. Fructans can also be classified according to their DP into small (2 to 4), medium (5 to 10), and relatively large chain lengths (11 to 60 fructose units). The term fructooligosaccharides (FOS) is used for short fructans with a DP of 3–5 derived from sucrose [22]; oligofructose (OF) is used for molecules with a DP of 3–10 derived from native inulin [23].

The biosynthesis of fructans begins with sucrose (Suc), to which fructose residues are added [4]. In plants, fructans are synthesized from Suc by the action of two or more enzymes known as fructosyltransferases. The first enzyme, 1-SST (sucrose:sucrose fructosyltransferase), initiates de novo fructan synthesis by catalyzing the transfer of a fructosyl residue from one Suc molecule to another, resulting in the formation of the trisaccharide 1-kestose. The second enzyme, 1-FFT (fructan:fructan 1-fructosyltransferase), transfers fructosyl residues from a fructan molecule with a DP of ≤3 to either another fructan molecule or a Suc. The actions of 1-SST and 1-FFT result in the formation of a mixture of fructan molecules with different chain lengths [13].

3. Functional Effects of Fructans

Worldwide, over 60% of functional food products are directed toward intestinal health, and additional therapeutic benefits of these products to human health are constantly being explored. Prebiotics are defined as “selectively fermented ingredients that allow specific changes, both in the composition and/or activity in the gastrointestinal microbiota that confers benefits upon host well-being and health” [24]. Moreover, prebiotics may suppress pathogen growth to improve overall health [25]. Current evidence indicates that beneficial bacteria reduce the risk of diseases through diverse mechanisms, including modulation of gut microbiota composition or function, and regulation of host epithelial and immunological responses. These effects may be revealed through changes in bacterial populations or metabolic activity [26]. Bacterial metabolism can confer a number of advantageous effects to the host, including the production of vitamins, modulation of the immune system, enhancement of digestion and absorption, inhibition of harmful bacterial species, and removal of carcinogens and other toxins. The resident microbiota is also known to consist of pathogens that can disrupt normal gut function and predispose the host toward disease if allowed to overgrow [27].

Fructans play protective roles in plants subjected to drought, salt, or cold stress [14]. However, the therapeutic potential of fructans in human health has only recently been explored. As described above, fructans are the most widely known and used prebiotics [28]. Of the many nondigestible food ingredients studied for their prebiotic potential, human trials favor ITFs, FOS, OF, and GOS [2932]. Fructans have been proposed as modulators of the microbial ecology and host physiology in animals and humans [33, 34] because they are not digested [9]. Although they are subjected to minor hydrolysis in the stomach, the human gut lacks the hydrolytic enzymes capable of digesting β linkages [35]. Therefore, fructans reach the colon relatively intact and eventually trigger a decrease in the pH, thereby altering the colonic environment [36]. The rate and extent of ITFs fermentation appear to be strongly influenced by the DP. FOS (low DP) are rapidly fermented in the proximal colon [37], whereas inulin (high DP) appears to have a more sustained fermentation profile that potentially enables protective effects in the distal colon [4, 38]. Acting as prebiotics, inulin, FOS, and GOS improve glucose, reduce triglycerides, modify lipid metabolism, and reduce plasma LPS. Additionally, they stimulate Lactobacillus and Bifidobacterium species to reduce the presence of pathogens in the gut and relieve constipation (Table 1). Other fructans, including soluble gut oligosaccharides, mimic the sugar chains found in the glycoproteins and glycolipids of gut epithelial cells, thereby preventing the adhesion of pathogenic microorganisms [39] and exerting direct antimicrobial effects [40] (Table 1).


EffectType of fructanDose/durationModelResultsReference

Decreasing blood glucoseFOS, inulin8 g/d for 14 days; 10% for 4 weeksDiabetic subjects; animal modelsSignificant reduction of mean fasting blood glucose levels. Improving glucose tolerance[4951]

Reduction in blood serum triacylglycerol levelsFOS, inulin4–34 g/d for 21–60 days; 10% for 3–5 weeksHealthy humans; obese animal modelsSignificant reduction in blood serum triacylglycerol levels[5254]

Improved lipid metabolismFOS, GOS, inulin, and agavins5%–10% for 21 day to 8 weeksObese animal modelsDecrease in body weight gain. Decrease in epididymal adipose tissue, inguinal adipose tissue, and subcutaneous adipose tissue. Reducing fat-mass development[41, 50, 51, 5559]

Stimulation of lactobacilli and bifidobacteria and decreasing pathogensFOS, GOS, and inulin2.5–34 g/d for 14–64 daysHealthy subjects and animal modelsStimulating the growth of bifidobacteria and contributing to the suppression of potential pathogenic bacteria[46, 60, 61]

Relief of constipationInulin, FOS, and GOS20–40 g/d for 19 daysConstipated humans and animal modelsInulin showing a better laxative effect than lactose and reducing functional constipation with only mild discomfort[62, 63]

Increased production of SCFAs and decreasing colon pHInulin, FOS, and agavins24 g/d for 5 weeks; 10% for 28 daysHealthy subjects; animal modelsSignificant increase of acetate, propionate, and butyrate. Significantly increasing activity of bacterial enzymes and decreasing the pH of digesta[36, 64, 65]

Improving mineral uptakeInulin, FOS, and agavins1–40 g/d for 9 days; 50–100 g/kg diet for 4 weeksMale healthy adolescents; animal modelsFOS stimulating fractional calcium absorption in male adolescents. A combination of different carbohydrates showing synergistic effects on intestinal Ca absorption and balance in rats[6669]

Regulated gut peptidesInulin, FOS, and agavins24 g/d for 5 weeks; 10% for 5 weeksHealthy subjects; animals modelsIncreasing plasma glucagon-like peptide-1 (GLP-1) concentrations and reducing ghrelin. Increasing endogenous GLP-2 production and consequently improving gut barrier functions[36, 41, 50, 57, 59]

Reducing body weight and energy intakeAgavins10% for 5 weeksMale healthy animal modelAgave fructans showing indications of prebiotic activity, particularly in relation to satiety and GLP-1 and ghrelin secretion. In this same study, the levels of butyric acid were higher for Agave  potatorum fructans[43]

Growth inhibition and prevention of adhesion of pathogenic microorganismsFOS170 mg/kg, 2 weeks of lactationBreast-fed infant; cocultures of Pseudomonas aeruginosa Oligosaccharides in human milk interfering with microbial adhesion. Reduction of exotoxin A in cultures of P. aeruginosa [39, 40]

Reduction of oxidative stress by reducing ROS levelsFOS, agavins10% for 4–8 weeksMale obese animal modelsFOS reducing TBARS urine. Lipopolysaccharides reduction in plasma. Improving the redox status by reducing the malondialdehyde serum levels and protein oxidative damage[9, 42, 65]

Stimulation of the immune systemFOS, GOS, and inulinSee Table 2

FOS: fructooligosaccharides; GOS: galactooligosaccharides; SCFAs: short chain fatty acids.

Effects of fructansDose fructan/durationModelReference

DC and T cells in lamina propria of the caecum and PGE2 in small intestine, colon, and caecum3% FOS for 12 daysMice treated with antibiotics and conventionalized with Clostridium  difficile [118]

In peripheral blood: ↑ CD4+/CD8+ ratio and ↓ B cells. In GALT: proportion of CD4+ cells and CD8+ cells, PP, and lamina propria cells and CD4+/CD8+ ratio in lamina propria0.87% FOS for 14 daysAdult dogs[119]

Synbiotics whole blood phagocyte activation level.1% FOS for 28 daysPiglets infected with S.  typhimurium [120]

counts of leucocytes, lymphocytes, neutrophils, CD2+ T cells, CD4+ T cells, CD8+ T cells, B cells, and macrophages in blood, % phagocytic activity of leucocytes and neutrophils in blood.3 g/d OF for 20 daysNewborn piglets[121]

ileal IgA concentration.2 g/d FOS and/or MOS for 14 daysAdult dogs[122]

blood neutrophils and blood lymphocytes.2 g FOS plus/1 g MOS for 14 daysAdult dogs[123]

rotavirus-specific IgA levels in serum and duration of a strong rotavirus-specific IgA response in faeces and % IgA and IgG positive B cell in the PP. serum rotavirus-specific IgG and Rhesus rotavirus antigen concentration in stools.1.25 g/L OF for 7 weeksMice (pups) infected with Rhesus rotavirus[124]

No change in protein, alb, serum Ig, secreting IgA, and IL-4 and IFN- secretion, antibodies against influenza B and pneumococcus.6 g OF/ITFs for 28 weeksHealthy elderly (>70 years)[125]

% CD4 and CD8 lymphocytes, phagocytic activity in granulocytes and monocytes and IL-6 mRNA expression in PBMCs. 8 g/day FOS, 3 weeksNursing home elderly (77–97 years)[126]

total faecal IgA, size of PP, total IgA secretion by PP cells and IL-10 and IFN- production from PP CD4+ T cells.0–7.5% FOS for 6 weeksFemale mice[127]

leucocyte counts, NK activity of splenocytes and peritoneal macrophage phagocytosis of Listeria  monocytogenes.2.5–10% FOS or OF for 6 weeksFemale mice[128]

total number of immune cells in PP, B lymphocytes in PP and T lymphocytes and CD4+/CD8+ ratio in PP in endotoxemic mice only.10% FOS for 16 daysFemale mice healthy or endotoxemic[129]

peripheral blood lymphocyte concentration.1% ITFs/MOS for 4 weeksSenior dogs[130]

total intestinal IgA, ileal and colonic polymeric Ig receptor expression, ileal IgA secretion rate, IgA response of PP cells, and % of B220+ IgA+ cells.5% FOS for 23–44 daysNewborn mice[131]

IL-10 and IFN- production in PP, secretory IgA concentration in ileum and caecum.10% FOS-enriched ITFs for 4 weeksMale rats[132]

NK activity. Prevention of the decrease in proportion of T cells with NK activity.6 g/d OF and ITFs (2 : 1 ratio) for 1 yearElderly free-living adults (age ≤ 70 years)[133]

Improved response to some vaccine components and increased lymphocyte proliferation to influenza vaccine components.4.95% FOS for 183 daysHealthy adults (age ≤ 65 years)[134]

T cells, MHCII on antigen-presenting cells in spleen, MLN, and thymus, IL-2 and IL-4 in blood.10% FOS/ITFs for 4 monthsMale rats[135]

Trend towards higher fecal sIgA.0.6 g (GOS/FOS)/100 mL formula for 32 weeksNewborn non-breast-fed infants[136]

Improved response to B cells, memory cytotoxic T cells, influenza-activated lymphocytes (CD69 and CD25) and IL-6 and IL10.4.95% FOS for 4 weeksHealthy adults (age ≤ 65 years)[137]

In pregnant females and pups no effect on serum IgG1, IgG2, IgA, or IgM. In colostrum and milk IgM.0.1% OF during lactationPregnant female dogs and pups[138]

severity of enterocyte sloughing.1% FOS or ITFs for 14 daysPuppies[139]

% CD19 (B) cells, CD3+ HLA-DR+ (activated T cells) and % ICAM−1 bearing lymphocytes and % CD3+ NK+ cells.9 g/d ITFs for 5 weeksAdults smokers and nonsmokers[140]

vaccine-specific faecal IgA and plasma IgG levels, peritoneal macrophage activity, mean fluorescence intensity of MHCII+ cells in spleen, IL-12 and IFN- production by splenocytes, and survival from Salmonella infection when given vaccine.5% mix (ITFs, FOS, and OF) for 1 weekFemale mice[141]

fecal sIgA.6 g/L GOS/FOS (9 : 1) for 26 weeksNewborn healthy infants[142]

NK activity, and IL-10, IL-6, IL-1, and TNF-.5.5 g GOS/d for 10 weeksElderly (64–79 years)[143]

DCs in PP, IL-2, IL-10, and IFN- from spleen and MNL cells. number and proportion of T cell receptor (TCR-) +CD8+ cells in spleen and CD45RA+ cells in MLN.5% ITFs for 4 weeksFemale rats[113]

total IgE, IgG1, IgG2, and IgG3; cow’s milk protein-specific IgG1. 8 g/L GOS/FOS for 6 monthsNewborn infants at risk for allergy[144]

intestinal sIgA.2.51–0.42 g/kg/d mix of GOS, XOS, OF, and ITFs (3.6 : 1 : 0.4 : 5) for 12 daysFemale rats induced with diphenoxylate[145]

IL-1 in macrophage cultures and fecal IgA.3–5% FOS for 30 daysFemale mice[146]

LPS in blood and LPS-induced increases in gene expression in IL-1 and LPS-induced decreases in gene expression in IL-13 in blood.5 g XOS, ITFs–XOS (3 : 1) for 4 weeksHealthy volunteers[147]

serum cortisol, TNF- and IL-6 after a LPS injection.0.10% levan-type fructan for 42 daysGrowing pigs[63]

fecal secretory IgA and fecal calprotectin and plasma C-reactive protein.5.5 g/d B-GOS (Bi2muno) for 12 weeksOverweight adults[148]

TGF- secretion by splenocytes and IFN- production and IL-5.GOS/ITFs (dose and duration data not shown)Healthy mice[149]

CD16/56 on natural killer T cells and IL-10 secretion, XOS and Bi-07 supplementation CD19 on B cells.8 g XOS or with 109 CFU Bi-07/d for 21 daysHealthy adults (25–65 years)[150]

cell-mediated immunity in terms of skin indurations and CD4+ T-lymphocyte population.20–60 g/kg FOS/ITFs for 12 weeksHealthy rats[151]

FOS: fructooligosaccharides; PGE2: prostaglandin E2; GALT: gut-associated lymphocyte tissue; CD: cluster of differentiation; PP: Peyer’s patch; OF: oligofructose; MOS: mannanoligosaccharides; IgA: immunoglobulin A; IgG; immunoglobulin G; ITFs: inulin-type fructan; IL: interleukin; PMBCs: peripheral blood mononuclear cells; NK: natural killer cells; MHC II: major histocompatibility complex II; GOS: galactooligosaccharides; HLA: human leukocyte antigen; ICAM-1: intercellular adhesion molecule 1; IFN-γ: interferon gamma; DC: dendritic cell; TCR: T cell receptor; MLN: mesenteric lymph nodes; XO: xylooligosaccharides; LPS: lipopolysaccharides.

Interestingly, fructans from Dasylirion spp. (DAS) and A. tequilana Gto. (TEQ) increased SCFAs production and decreased colon pH in in vitro studies [41]. Furthermore, supplementation of the mouse diet with Agave fructans (TEQ and DAS) has been shown to increase secretion of GLP-1 and its precursor, proglucagon mRNA, in all colonic segments of the mouse. These results suggest that fermentable fructans of different botanical origins and with differing chemical structures are able to promote the production of satietogenic/incretin peptides in the lower part of the gut [41] (Table 1). Moreover, Agave fructans have been shown to have physiological effects on lipid metabolism [41, 42] and reduce oxidative stress in conjunction with phenolic compounds in in vitro and in vivo assays [42] (Table 1). For the first time, the effect of agavins from Agave angustifolia and Agave potatorum as prebiotics has been reported showing satiety effect as well as an increment on GLP-1 and a decrement on ghrelin in an animal model [43] (Table 1).

Studies have been performed to determine whether probiotics reduce cancer risk. To maximize the effect of a prebiotic compound, the prebiotic would need to ferment in the distal colon, where proteolytic fermentation predominates and toxic metabolites such as ammonia, hydrogen sulfide, and cresol are produced [44, 45]. A recent study by Gomez et al. was the first to investigate the effect of Agave fructan fermentation on complex fecal microbiota in vitro [46] (Table 1). The first clinical trial in humans with Agave fructans was very promising, as Agave treatment improved laxation [47]. Other carbohydrates, including glucooligosaccharides, isomaltooligosaccharides, lactulose, mannanoligosaccharides (MOS), nigerooligosaccharides, oat β-glucans, raffinose, soybean oligosaccharides, transgalactooligosaccharides, and xylooligosaccharides, are considered candidate prebiotics [31, 48]; however, more research is required.

4. Immunomodulatory Effects of Fructans

The consumption of prebiotics can modulate immune parameters in gut-associated lymphoid tissue (GALT), secondary lymphoid tissues, and peripheral circulation [70]. GALT functions to distinguish between harmful and innocuous agents and protects against infections while simultaneously avoiding the generation of hypersensitivity reactions to commensal bacteria and harmless antigens [7173]. In inductive GALT, more structured and localized sites of antigen processing and presentation are distinguished in areas such as Peyer’s patches (PPs), mesenteric lymph nodes (MLNs), the appendix, and isolated lymph nodes. GALT also contains effector sites with more diffuse organization, containing previously activated and differentiated cells that performed effector functions (Figure 2). Joint activity of the inductive and effector sites generates a rich response in immunoglobulin A (IgA) and cellular immunity, with robust cytotoxic regulatory functions and memory at the level of the mucosa and serum [74]. The intestinal epithelium provides a physical barrier that separates the trillions of commensal bacteria in the intestinal lumen from the underlying lamina propria (LP) and the deeper intestinal layers. Microfold cells (M cells), B cells (especially IgA-producing plasma cells), T cells, macrophages, and dendritic cells (DCs) in the LP are located directly below the intestinal epithelium (Figure 2). M cells are part of the epithelial layer covering the PP and specialize in transporting antigens from the lumen to GALT [75].

T and B cells are activated after initial contact with the antigen at inductive sites. These cells then proliferate, differentiate, and migrate to various effector sites, such as the LP or the intestinal epithelium, where a single population of iIELs (intestinal intraepithelial lymphocytes) and some DCs are located between the enterocytes [7678] (Figure 2).

In fact, iIELs provide a cellular defense against any individual antigen [79]. Meanwhile, DCs are potent antigen-presenting cells critical for the induction of downstream adaptive immune responses [80]. For instance, several subsets of DCs have been identified within the PP that possess either Th1- or Th2-polarizing ability [81]. The CD103+ subset has been found within the small intestinal LP, MLN, and PP, as well as the colonic LP. CD103+ DCs have FoxP3+ Treg-polarizing ability, as well as the ability to imprint gut-homing T cells; expression of the a4b7 integrin on conventional T cells and Treg cells involved in directing gut tropism ensures their ability to be imprinted [82, 83]. CD103+ DC subsets have also been shown to induce Th17 polarization and IgA class switching [84, 85]. Moreover, all DC subsets and antigen-presenting cells, including macrophages, are equipped with a battery of pattern recognition receptors (PRRs). These receptors can detect molecular patterns of invading microorganisms or endogenous “danger” signals and stimulate the immune response. PRRs are expressed on the cell surface and intracellularly are extremely diverse and capable of detecting a wide range of molecular species, including proteins, carbohydrates, lipids, and nucleic acids [86]. The Toll-like receptor (TLRs) family is the most intensely studied family of PRRs on DCs. Triggering TLRs on DCs is thought to be critical for their functional maturation to immunogenic DCs and for their ability to prime naive T cells in response to infection. Therefore, TLR activation couples innate and adaptive immunity [87]. TLR-mediated recognition of commensal microorganisms may also play important roles in tissue homeostasis, as recent studies have shown that TLR signaling by DCs was required to maintain immune homeostasis and tolerance to gut microbiota [88]. Interestingly, Tregs are also abundant at host-microbiota interfaces. Studies have suggested that commensal microbiota can stimulate the generation of Tregs and Th17 cells [89]. These results highlight the importance of diet and the microbiota in the establishment and configuration of the immune system of the intestinal mucosa. However, whether prebiotic compounds directly affect immune components or whether they act exclusively through the modulation of the endogenous intestinal microbiota remains unclear.

4.1. Indirect Mechanisms of Fructan Health Effects

Prebiotics and probiotics may have indirect immunomodulatory functions through their actions on nonimmune cells, such as epithelial cells. However, they may also exert immune system-independent effects by selectively stimulating the growth and/or activity of beneficial intestinal bacteria, such as Lactobacillus and Bifidobacterium species, which results in the restoration of the normal composition of the intestinal microbiota [90]. Mutualism between the host and its microbiota is fundamental for maintaining homeostasis in a healthy individual [91]. Commensal bacteria provide the host with essential nutrients. They also metabolize indigestible compounds, defend against the colonization of opportunistic pathogens, and contribute to the development of intestinal architecture in addition to stimulating the immune system [92]. In fact, intestinal immune and metabolic homeostasis in mammals is largely maintained by interactions between the gut microbiota and GALT [93]. The host actively engages the gut microbiota and controls its composition by secreting antimicrobial peptides and immunoglobulins. Conversely, commensals shape the gut-associated immune system by controlling the prevalence of distinct T cell populations [94]. Bacteroides fragilis protects mice from infection by Helicobacter hepaticus through several immunological mechanisms, including suppression of IL-17 production [95]. These commensals also express capsular zwitterionic polysaccharide A, which is a cognate antigen to effector CD4+ T cells [92]. Other zwitterionic polysaccharides, such as type 1 capsule of Streptococcus pneumoniae, can also modify inflammatory responses in animal models by stimulating IL-10-producing CD4+ T cells [96]. Moreover, bacterial symbionts, such as Bacteroides, Barnesiella, and Turicibacter, interact with CD8+ cytotoxic T cells in the mucosal compartment of the small intestine and colon [97].

Other indirect pathways by which fructans exert immunomodulatory effects include the production of SCFAs, which are the fermentation products of fructans. Inulin fermentation increases the production of SCFAs (acetate, propionate, and butyrate), lactic acid, and hydrogen (H2), while decreasing the pH of the colonic environment [36]. Bifidobacterium species are able to use some monosaccharides in a unique manner to ultimately generate SCFAs [98] and acidify the colonic environment. The increase in SCFAs antagonizes the growth of some pathogenic bacterial strains [99] and favors mucin production in the colon [100]. SCFAs bind to SCFAs receptors on GALT immune cells [101103], activating G protein-coupled receptors (GPR) [104], such as GPR41 and GPR43 [101, 102, 104]. This binding affects the recruitment of leukocytes to inflammatory sites [105, 106] and suppresses the production of proinflammatory cytokines and chemokines [106108]. GPR43 is highly expressed in polymorphonuclear cells (PMNs, i.e., neutrophils) and is lowly expressed in peripheral blood mononuclear cells (PBMCs) and purified monocytes. Conversely, GPR41 is expressed in PBMCs but not in PMNs, monocytes, or DCs [102]. Importantly, butyrate decreases the glutamine requirement for epithelial cells and alters epithelial cell gene expression [71, 109]. The mechanism for the indirect effect of fructans on the immune system is shown in Figure 3.

4.2. Direct Mechanism: Pattern Recognition Receptors

In addition to the indirect effects of fructans and their fermentation products on the microbiota, the direct effects of fructans on the signaling of immune cells have gained attention as an additional pathway of immunomodulation. ITFs have been reported to interact directly with GALT components, such as gut dendritic cells (DCs) and intraepithelial lymphocytes (iIELs), through receptor ligation of PRRs [7]. Signaling through PRRs, such as TLRs (Toll-like receptors), is considered the starting point of innate immune system activation against various environmental factors, including microbes and antigens. The innate immune system enables appropriate adaptive immune responses to be generated through the activation of multiple specific immunocompetent clones [110]. TLRs play an important role in initial innate immune responses, which includes cytokine synthesis and activating acquired immunity. The β(2→1)-linked fructans can provide a direct signal to human immune cells primarily by activating TLR2 and to a lesser extent TLR4, TLR5, TLR7, TLR8, and NOD2. β(2→1)-linked fructans stimulation results in NF-κB/AP-1 activation, further suggesting that β(2→1)-fructans are specific ligands for TLR2. However, chain length is important for the induced activation pattern and IL-10/IL-12 ratios stimulated by β(2→1)-fructans [111, 112]. In fact, ITFs increase the proportion of DCs in PPs and increase the secretion of IL-2, IL-10, and interferon-γ from the spleen and MLNs. Additionally, ITFs reduce the number and proportion of T cell receptor (TCR-) αβ+ CD8+ cells in the spleen and CD45RA+ cells in the MLNs [113] (Table 2). Furthermore, TLR4 appears to be involved in levan β(2→6)-fructans pattern recognition. Oral administration of levans in vivo significantly reduced IgE serum levels and Th2 response in mice immunized with ovalbumin [8].

A fructose receptor may exist on immune cells, as receptors for β-glucan [114] and mannose [115] have been identified on the surface of immune cells. Oligofructose has also been shown to bind to receptors on pathogenic bacteria, preventing them from attaching to the epithelial membrane [116]. Furthermore, ITFs treatment of gut epithelial cells can modulate the innate immune barrier by modifying the integrity of epithelial tight junctions or by altering signals from the epithelial cells to the underlying immune cells [117].

Thirty-six fructan studies reporting immune outcomes have been conducted in mice, rats, pigs, dogs, and humans, and these investigations are summarized in Table 2. These reports show that fructans may have specific effects on different immune system components.

5. Fructans Act as ROS Scavengers

Because inulins and agavins have health benefits, improve blood metabolic parameters [41, 52], reduce colonic pH [152], increase SCFAs production [36, 43, 69], and stimulate the immune system [48], interest has developed in the antioxidant capacity of fructans. As in plants, fructans and other carbohydrates have been shown to scavenge ROS [153157]. ROS include free radicals such as the superoxide anion (), hydroxyl radical (OH), and nonradical molecules such as hydrogen peroxide (H2O2) and singlet oxygen (1O2). These molecules attack DNA, lipids, and proteins resulting in cellular damage [158]. Fructans, galactooligosaccharides (GOS), arabinoxylans, β-glucans, and fructooligosaccharides (FOS) might act as ROS scavengers in plants [159] because they have strong antioxidant activity in vitro. Raffinose appears to be a moderate ROS scavenger [160].

Recently reports have suggested that fructans possess antioxidant activity in in vivo models. A putative role for oligofructoses in counteracting the prooxidative effects of a high fructose diet has been demonstrated in rats. The addition of fructans to the diet may provide an early defense against oxidative stress and may act before the activation of the endogenous ROS detoxification systems [65]. In an indirect mechanism, these nondigestible carbohydrates might serve as ROS scavengers, which suggests that inulin can protect the colonic mucosa by acting as a barrier against oxidative stress in addition to its positive prebiotic effect. This hypothesis is consistent with the recently proposed ROS scavenging capability of inulin [65, 161] and the reported effects of SCFAs, which induce the expression of crucial antioxidant enzymes, such as glutathione S-transferases (GSTs) [162]. Li et al. showed that, in aged mice, synthetic oligosaccharides increase the activity of antioxidant enzymes [161]. By contrast, oligofructose has been shown to reduce the expression of NADPH oxidase in the colons of obese mice [51]. Moreover, intraperitoneal administration of synthetic oligosaccharides stimulates a dose-dependent decrease in lipid peroxidation, which supports the in vivo ROS scavenging capability of certain sugars [161]. Furthermore, agavins from Agave tequilana have been shown to improve the redox status in hypercholesterolemic mice by reducing malondialdehyde serum levels and oxidative protein damage. These results could be attributed to a reduction in the generation of oxidative products during digestion and colonic fermentation [42]. Additionally, polyphenol studies have indicated that metabolism in the large intestine is positively affected by prebiotic fructooligosaccharides, which have a synergistic effect with polyphenol to counteract oxidative stress in in vivo models [163].

6. Conclusion

Prebiotic consumption is undoubtedly associated with several health benefits. In this review, we assessed the potential immunomodulatory and antioxidants mechanisms of the prebiotic fructans as well as the impact of fructans on immune health. Some preliminary data have convincingly suggested that fructan consumption can modulate immune parameters in GALT. Additionally, fructans may act as ROS scavengers providing an increase in antioxidant defenses partially through the activation of endogenous ROS detoxification systems. Further studies will be required to fully understand and elucidate the mechanisms of action for fructans on GALT in various disease models.

Conflict of Interests

The authors declare that there is no conflict of interests regarding the publication of this paper.

References

  1. M. G. Lopez, N. A. Mancilla-Margalli, and G. Mendoza-Diaz, “Molecular structures of fructans from Agave tequilana Weber var. azul,” Journal of Agricultural and Food Chemistry, vol. 51, no. 27, pp. 7835–7840, 2003. View at: Publisher Site | Google Scholar
  2. J. van Loo, P. Coussement, L. de Leenheer, H. Hoebregs, and G. Smits, “On the presence of inulin and oligofructose as natural ingredients in the western diet,” Critical Reviews in Food Science and Nutrition, vol. 35, no. 6, pp. 525–552, 1995. View at: Publisher Site | Google Scholar
  3. C. J. Pollock and A. J. Cairns, “Fructan metabolism in grasses and cereals,” Annual Review of Plant Physiology and Plant Molecular Biology, vol. 42, no. 1, pp. 77–101, 1991. View at: Publisher Site | Google Scholar
  4. G. Kelly, “Inulin-type prebiotics—a review: part 1,” Alternative Medicine Review, vol. 13, no. 4, pp. 315–329, 2008. View at: Google Scholar
  5. N. A. Mancilla-Margalli and M. G. Lopez, “Water-soluble carbohydrates and fructan structure patterns from Agave and Dasylirion species,” Journal of Agricultural and Food Chemistry, vol. 54, no. 20, pp. 7832–7839, 2006. View at: Publisher Site | Google Scholar
  6. C.-C. Tsai, C.-R. Lin, H.-Y. Tsai et al., “The immunologically active oligosaccharides isolated from wheatgrass modulate monocytes via toll-like receptor-2 signaling,” The Journal of Biological Chemistry, vol. 288, no. 24, pp. 17689–17697, 2013. View at: Publisher Site | Google Scholar
  7. L. Vogt, D. Meyer, G. Pullens et al., “Immunological properties of inulin-type fructans,” Critical Reviews in Food Science and Nutrition, vol. 55, no. 3, pp. 414–436, 2014. View at: Publisher Site | Google Scholar
  8. Q. Xu, T. Yajima, W. Li, K. Saito, Y. Ohshima, and Y. Yoshikai, “Levan (β-2, 6-fructan), a major fraction of fermented soybean mucilage, displays immunostimulating properties via Toll-like receptor 4 signalling: induction of interleukin-12 production and suppression of T-helper type 2 response and immunoglobulin E production,” Clinical & Experimental Allergy, vol. 36, no. 1, pp. 94–101, 2006. View at: Publisher Site | Google Scholar
  9. W. van den Ende, D. Peshev, and L. de Gara, “Disease prevention by natural antioxidants and prebiotics acting as ROS scavengers in the gastrointestinal tract,” Trends in Food Science and Technology, vol. 22, no. 12, pp. 689–697, 2011. View at: Publisher Site | Google Scholar
  10. G. A. F. Hendry, “Evolutionary origins and natural functions of fructans—a climatological, biogeographic and mechanistic appraisal,” New Phytologist, vol. 123, no. 1, pp. 3–14, 1993. View at: Google Scholar
  11. A. Cardelle-Cobas, N. Corzo, A. Olano, C. Peláez, T. Requena, and M. Ávila, “Galactooligosaccharides derived from lactose and lactulose: influence of structure on Lactobacillus, Streptococcus and Bifidobacterium growth,” International Journal of Food Microbiology, vol. 149, no. 1, pp. 81–87, 2011. View at: Publisher Site | Google Scholar
  12. G. Iniguez-Covarrubias, R. Díaz-Teres, R. Sanjuan-Duenas, J. Anzaldo-Hernández, and R. M. Rowell, “Utilization of by-products from the tequila industry. Part 2: potential value of Agave tequilana Weber azul leaves,” Bioresource Technology, vol. 77, no. 2, pp. 101–108, 2001. View at: Publisher Site | Google Scholar
  13. I. Vijn and S. Smeekens, “Fructan: more than a reserve carbohydrate?” Plant Physiology, vol. 120, no. 2, pp. 351–359, 1999. View at: Publisher Site | Google Scholar
  14. T. Ritsema and S. Smeekens, “Fructans: beneficial for plants and humans,” Current Opinion in Plant Biology, vol. 6, no. 3, pp. 223–230, 2003. View at: Publisher Site | Google Scholar
  15. N. Kaur and A. K. Gupta, “Applications of inulin and oligofructose in health and nutrition,” Journal of Biosciences, vol. 27, no. 7, pp. 703–714, 2002. View at: Publisher Site | Google Scholar
  16. N. J. Chatterton and P. A. Harrison, “Fructan oligomers in Poa ampla,” New Phytologist, vol. 136, no. 1, pp. 3–10, 1997. View at: Publisher Site | Google Scholar
  17. J.-Z. Wei, N. J. Chatterton, P. A. Harrison, R. R.-C. Wang, and S. R. Larson, “Characterization of fructan biosynthesis in big bluegrass (Poa secunda),” Journal of Plant Physiology, vol. 159, no. 7, pp. 705–715, 2002. View at: Publisher Site | Google Scholar
  18. D. P. Livingston, N. J. Chatterton, and P. A. Harrison, “Structure and quantity of fructan oligomers in oat (Avena spp.),” New Phytologist, vol. 123, no. 4, pp. 725–734, 1993. View at: Publisher Site | Google Scholar
  19. I. M. Sims, C. J. Pollock, and R. Horgan, “Structural analysis of oligomeric fructans from excised leaves of Lolium temulentum,” Phytochemistry, vol. 31, no. 9, pp. 2989–2992, 1992. View at: Publisher Site | Google Scholar
  20. N. Pavis, N. J. Chatterton, P. A. Harrison et al., “Structure of fructans in roots and leaf tissues of Lolium perenne,” New Phytologist, vol. 150, no. 1, pp. 83–95, 2001. View at: Publisher Site | Google Scholar
  21. N. Shiomi, “Properties of fructosyltransferases involved in the synthesis of fructan in liliaceous plants,” Journal of Plant Physiology, vol. 134, no. 2, pp. 151–155, 1989. View at: Publisher Site | Google Scholar
  22. I. G. Carabin and W. Gary Flamm, “Evaluation of safety of inulin and oligofructose as dietary fiber,” Regulatory Toxicology and Pharmacology, vol. 30, no. 3, pp. 268–282, 1999. View at: Publisher Site | Google Scholar
  23. M. B. Roberfroid, “Concepts in functional foods: the case of inulin and oligofructose,” Journal of Nutrition, vol. 129, no. 7, pp. 1398S–1401s, 1999. View at: Google Scholar
  24. M. B. Roberfroid, “Inulin-type fructans: functional food ingredients,” Journal of Nutrition, vol. 137, no. 11, supplement, pp. 2493S–2502S, 2007. View at: Google Scholar
  25. M. B. Roberfroid, “Prebiotics: preferential substrates for specific germs?” American Journal of Clinical Nutrition, vol. 73, no. 2, supplement, pp. 406S–409S, 2001. View at: Google Scholar
  26. M. E. Sanders, F. Guarner, R. Guerrant et al., “An update on the use and investigation of probiotics in health and disease,” Gut, vol. 62, no. 5, pp. 787–796, 2013. View at: Publisher Site | Google Scholar
  27. S. Kolida and G. R. Gibson, “Prebiotic capacity of inulin-type fructans,” Journal of Nutrition, vol. 137, no. 11, supplement, pp. 2503S–2506S, 2007. View at: Google Scholar
  28. S. H. Al-Sheraji, A. Ismail, M. Y. Manap, S. Mustafa, R. M. Yusof, and F. A. Hassan, “Prebiotics as functional foods: a review,” Journal of Functional Foods, vol. 5, no. 4, pp. 1542–1553, 2013. View at: Publisher Site | Google Scholar
  29. G. R. Gibson, H. M. Probert, J. Van Loo, R. A. Rastall, and M. B. Roberfroid, “Dietary modulation of the human colonic microbiota: updating the concept of prebiotics,” Nutrition Research Reviews, vol. 17, no. 2, pp. 259–275, 2004. View at: Publisher Site | Google Scholar
  30. E. Menne, N. Guggenbuhl, and M. Roberfroid, “Fn-type chicory inulin hydrolysate has a prebiotic effect in humans,” Journal of Nutrition, vol. 130, no. 5, pp. 1197–1199, 2000. View at: Google Scholar
  31. Y. Bouhnik, B. Flourié, L. D'Agay-Abensour et al., “Administration of transgalacto-oligosaccharides increases fecal bifidobacteria and modifies colonic fermentation metabolism in healthy humans,” Journal of Nutrition, vol. 127, no. 3, pp. 444–448, 1997. View at: Google Scholar
  32. M. Ito, Y. Deguchi, K. Matsumoto, M. Kimura, N. Onodera, and T. Yajima, “Influence of galactooligosaccharides on the human fecal microflora,” Journal of Nutritional Science and Vitaminology, vol. 39, no. 6, pp. 635–640, 1993. View at: Publisher Site | Google Scholar
  33. P. D. Cani, R. Bibiloni, C. Knauf et al., “Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice,” Diabetes, vol. 57, no. 6, pp. 1470–1481, 2008. View at: Publisher Site | Google Scholar
  34. N. M. Delzenne, A. M. Neyrinck, and P. D. Cani, “Modulation of the gut microbiota by nutrients with prebiotic properties: consequences for host health in the context of obesity and metabolic syndrome,” Microbial Cell Factories, vol. 10, supplement 1, article S10, 2011. View at: Publisher Site | Google Scholar
  35. F. Di Bartolomeo, J. B. Startek, and W. van den Ende, “Prebiotics to fight diseases: reality or fiction?” Phytotherapy Research, vol. 27, no. 10, pp. 1457–1473, 2013. View at: Publisher Site | Google Scholar
  36. J. Tarini and T. M. S. Wolever, “The fermentable fibre inulin increases postprandial serum short-chain fatty acids and reduces free-fatty acids and ghrelin in healthy subjects,” Applied Physiology, Nutrition and Metabolism, vol. 35, no. 1, pp. 9–16, 2010. View at: Publisher Site | Google Scholar
  37. J. J. Rumessen, S. Bodé, O. Hamberg, and E. Gudmand-Høyer, “Fructans of Jerusalem artichokes: intestinal transport, absorption, fermentation, and influence on blood glucose, insulin, and C-peptide responses in healthy subjects,” American Journal of Clinical Nutrition, vol. 52, no. 4, pp. 675–681, 1990. View at: Google Scholar
  38. T. van de Wiele, N. Boon, S. Possemiers, H. Jacobs, and W. Verstraete, “Inulin-type fructans of longer degree of polymerization exert more pronounced in vitro prebiotic effects,” Journal of Applied Microbiology, vol. 102, no. 2, pp. 452–460, 2007. View at: Publisher Site | Google Scholar
  39. D. Dai, N. N. Nanthkumar, D. S. Newburg, and W. A. Walker, “Role of oligosaccharides and glycoconjugates in intestinal host defense,” Journal of Pediatric Gastroenterology and Nutrition, vol. 30, supplement 2, pp. S23–S33, 2000. View at: Publisher Site | Google Scholar
  40. M. Ortega-González, F. Sánchez De Medina, C. Molina-Santiago et al., “Fructooligosacharides reduce Pseudomonas aeruginosa PAO1 pathogenicity through distinct mechanisms,” PLoS ONE, vol. 9, no. 1, Article ID e85772, 2014. View at: Publisher Site | Google Scholar
  41. J. E. Urías-Silvas, P. D. Cani, E. Delmée, A. Neyrinck, M. G. López, and N. M. Delzenne, “Physiological effects of dietary fructans extracted from Agave tequilana Gto. and Dasylirion spp,” British Journal of Nutrition, vol. 99, no. 2, pp. 254–261, 2008. View at: Google Scholar
  42. S. G. Sáyago-Ayerdi, R. Mateos, R. I. Ortiz-Basurto et al., “Effects of consuming diets containing Agave tequilana dietary fibre and jamaica calyces on body weight gain and redox status in hypercholesterolemic rats,” Food Chemistry, vol. 148, pp. 54–59, 2014. View at: Publisher Site | Google Scholar
  43. P. A. Santiago-García and M. G. López, “Agavins from Agave angustifolia and Agave potatorum affect food intake, body weight gain and satiety-related hormones (GLP-1 and ghrelin) in mice,” Food & Function, vol. 5, no. 12, pp. 3311–3319, 2014. View at: Publisher Site | Google Scholar
  44. M. I. McBurney, P. J. Van Soest, and J. L. Jeraci, “Colonic carcinogenesis: the microbial feast or famine mechanism,” Nutrition and Cancer, vol. 10, no. 1-2, pp. 23–28, 1987. View at: Publisher Site | Google Scholar
  45. V. De Preter, T. Vanhoutte, G. Huys et al., “Effects of Lactobacillus casei Shirota, Bifidobacterium breve, and oligofructose-enriched inulin on colonic nitrogen-protein metabolism in healthy humans,” The American Journal of Physiology—Gastrointestinal and Liver Physiology, vol. 292, no. 1, pp. G358–G368, 2007. View at: Publisher Site | Google Scholar
  46. E. Gomez, K. M. Tuohy, G. R. Gibson, A. Klinder, and A. Costabile, “In vitro evaluation of the fermentation properties and potential prebiotic activity of Agave fructans,” Journal of Applied Microbiology, vol. 108, no. 6, pp. 2114–2121, 2010. View at: Publisher Site | Google Scholar
  47. H. D. Holscher, J. L. Doligale, L. L. Bauer et al., “Gastrointestinal tolerance and utilization of agave inulin by healthy adults,” Food & Function, vol. 5, no. 6, pp. 1142–1149, 2014. View at: Publisher Site | Google Scholar
  48. A. R. Lomax and P. C. Calder, “Prebiotics, immune function, infection and inflammation: a review of the evidence,” British Journal of Nutrition, vol. 101, no. 5, pp. 633–658, 2009. View at: Publisher Site | Google Scholar
  49. K. Yamashita, K. Kawai, and M. Itakura, “Effects of fructo-oligosaccharides on blood glucose and serum lipids in diabetic subjects,” Nutrition Research, vol. 4, no. 6, pp. 961–966, 1984. View at: Publisher Site | Google Scholar
  50. P. D. Cani, C. Knauf, M. A. Iglesias, D. J. Drucker, N. M. Delzenne, and R. Burcelin, “Improvement of glucose tolerance and hepatic insulin sensitivity by oligofructose requires a functional glucagon-like peptide 1 receptor,” Diabetes, vol. 55, no. 5, pp. 1484–1490, 2006. View at: Publisher Site | Google Scholar
  51. A. Everard, V. Lazarevic, M. Derrien et al., “Responses of gut microbiota and glucose and lipid metabolism to prebiotics in genetic obese and diet-induced leptin-resistant mice,” Diabetes, vol. 60, no. 11, pp. 2775–2786, 2011. View at: Publisher Site | Google Scholar
  52. F. Brighenti, “Dietary fructans and serum triacylglycerols: a meta-analysis of randomized controlled trials,” Journal of Nutrition, vol. 137, no. 11, supplement, pp. 2552S–2556S, 2007. View at: Google Scholar
  53. C. Daubioul, N. Rousseau, R. Demeure et al., “Dietary fructans, but not cellulose, decrease triglyceride accumulation in the liver of obese Zucker fa/fa rats,” Journal of Nutrition, vol. 132, no. 5, pp. 967–973, 2002. View at: Google Scholar
  54. R. A. Reimer and J. C. Russell, “Glucose tolerance, lipids, and GLP-1 secretion in JCR:LA-cp rats fed a high protein fiber diet,” Obesity, vol. 16, no. 1, pp. 40–46, 2008. View at: Publisher Site | Google Scholar
  55. E. Sakaguchi, C. Sakoda, and Y. Toramaru, “Caecal fermentation and energy accumulation in the rat fed on indigestible oligosaccharides,” British Journal of Nutrition, vol. 80, no. 5, pp. 469–476, 1998. View at: Google Scholar
  56. C. A. Daubioul, H. S. Taper, L. D. de Wispelaere, and N. M. Delzenne, “Dietary oligofructose lessens hepatic steatosis, but does not prevent hypertriglyceridemia in obese Zucker rats,” Journal of Nutrition, vol. 130, no. 5, pp. 1314–1319, 2000. View at: Google Scholar
  57. E. Delmée, P. D. Cani, G. Gual et al., “Relation between colonic proglucagon expression and metabolic response to oligofructose in high fat diet-fed mice,” Life Sciences, vol. 79, no. 10, pp. 1007–1013, 2006. View at: Publisher Site | Google Scholar
  58. J. A. Jamieson, N. R. Ryz, C. G. Taylor, and H. A. Weiler, “Dietary long-chain inulin reduces abdominal fat but has no effect on bone density in growing female rats,” British Journal of Nutrition, vol. 100, no. 2, pp. 451–459, 2008. View at: Google Scholar
  59. P. D. Cani, S. Possemiers, T. van de Wiele et al., “Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability,” Gut, vol. 58, no. 8, pp. 1091–1103, 2009. View at: Publisher Site | Google Scholar
  60. B. Kleessen, S. Schwarz, A. Boehm et al., “Jerusalem artichoke and chicory inulin in bakery products affect faecal microbiota of healthy volunteers,” British Journal of Nutrition, vol. 98, no. 3, pp. 540–549, 2007. View at: Publisher Site | Google Scholar
  61. S. Wang, H. Zhu, C. Lu et al., “Fermented milk supplemented with probiotics and prebiotics can effectively alter the intestinal microbiota and immunity of host animals,” Journal of Dairy Science, vol. 95, no. 9, pp. 4813–4822, 2012. View at: Publisher Site | Google Scholar
  62. H. Hidaka, Y. Tashiro, and T. Eida, “Proliferation of bifidobacteria by oligosaccharides and their useful effect on human health,” Bifidobacteria and Microflora, vol. 10, no. 1, pp. 65–79, 1991. View at: Publisher Site | Google Scholar
  63. J. Li and I. H. Kim, “Effects of levan-type fructan supplementation on growth performance, digestibility, blood profile, fecal microbiota, and immune responses after lipopolysaccharide challenge in growing pigs,” Journal of Animal Science, vol. 91, no. 11, pp. 5336–5343, 2013. View at: Publisher Site | Google Scholar
  64. Z. Zduńczyk, J. Juśkiewicz, and I. Estrella, “Cecal parameters of rats fed diets containing grapefruit polyphenols and inulin as single supplements or in a combination,” Nutrition, vol. 22, no. 9, pp. 898–904, 2006. View at: Publisher Site | Google Scholar
  65. J. Busserolles, E. Gueux, E. Rock, C. Demigné, A. Mazur, and Y. Rayssiguier, “Oligofructose protects against the hypertriglyceridemic and pro-oxidative effects of a high fructose diet in rats,” Journal of Nutrition, vol. 133, no. 6, pp. 1903–1908, 2003. View at: Google Scholar
  66. E. G. H. M. van den Heuvel, T. Muys, W. van Dokkum, and G. Schaafsma, “Oligofructose stimulates calcium absorption in adolescents,” The American Journal of Clinical Nutrition, vol. 69, no. 3, pp. 544–548, 1999. View at: Google Scholar
  67. H. Younes, C. Coudray, J. Bellanger, C. Demigné, Y. Rayssiguier, and C. Rémésy, “Effects of two fermentable carbohydrates (inulin and resistant starch) and their combination on calcium and magnesium balance in rats,” British Journal of Nutrition, vol. 86, no. 4, pp. 479–485, 2001. View at: Publisher Site | Google Scholar
  68. K. E. Scholz-Ahrens, P. Ade, B. Marten et al., “Prebiotics, probiotics, and synbiotics affect mineral absorption, bone mineral content, and bone structure,” Journal of Nutrition, vol. 137, no. 3, supplement 2, pp. 838S–846S, 2007. View at: Google Scholar
  69. M. I. García-Vieyra, A. del Real, and M. G. López, “Agave fructans: their effect on mineral absorption and bone mineral content,” Journal of Medicinal Food, vol. 17, no. 11, pp. 1247–1255, 2014. View at: Publisher Site | Google Scholar
  70. P. Bodera, “Influence of prebiotics on the human immune system (GALT),” Recent Patents on Inflammation and Allergy Drug Discovery, vol. 2, no. 2, pp. 149–153, 2008. View at: Publisher Site | Google Scholar
  71. I. R. Sanderson, “Dietary modulation of GALT,” Journal of Nutrition, vol. 137, supplement 11, pp. 2557S–2562S, 2007. View at: Google Scholar
  72. L. Mayer, “Mucosal immunity,” Pediatrics, vol. 111, no. 6, part 3, pp. 1595–1600, 2003. View at: Google Scholar
  73. T. T. MacDonald and G. Monteleone, “Immunity, inflammation, and allergy in the gut,” Science, vol. 307, no. 5717, pp. 1920–1925, 2005. View at: Publisher Site | Google Scholar
  74. A. M. Mowat, “Anatomical basis of tolerance and immunity to intestinal antigens,” Nature Reviews Immunology, vol. 3, no. 4, pp. 331–341, 2003. View at: Publisher Site | Google Scholar
  75. E. Ramiro-Puig, F. J. Pérez-Cano, C. Castellote, A. Franch, and M. Castell, “The bowel: a key component of the immune system,” Revista Espanola de Enfermedades Digestivas, vol. 100, no. 1, pp. 29–34, 2008. View at: Google Scholar
  76. M. Rescigno, M. Urbano, B. Valzasina et al., “Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria,” Nature Immunology, vol. 2, no. 4, pp. 361–367, 2001. View at: Publisher Site | Google Scholar
  77. B. Jabri and E. Ebert, “Human CD8+ intraepithelial lymphocytes: a unique model to study the regulation of effector cytotoxic T lymphocytes in tissue,” Immunological Reviews, vol. 215, no. 1, pp. 202–214, 2007. View at: Publisher Site | Google Scholar
  78. J. H. Niess, S. Brand, X. Gu et al., “CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance,” Science, vol. 307, no. 5707, pp. 254–258, 2005. View at: Publisher Site | Google Scholar
  79. H. Cheroutre, “IELs: enforcing law and order in the court of the intestinal epithelium,” Immunological Reviews, vol. 206, no. 1, pp. 114–131, 2005. View at: Publisher Site | Google Scholar
  80. R. M. Steinman, “Decisions about dendritic cells: past, present, and future,” Annual Review of Immunology, vol. 30, no. 1, pp. 1–22, 2012. View at: Publisher Site | Google Scholar
  81. J. Shiu and T. G. Blanchard, “Dendritic cell function in the host response to Helicobacter pylori infection of the gastric mucosa,” Pathogens and Disease, vol. 67, no. 1, pp. 46–53, 2013. View at: Publisher Site | Google Scholar
  82. J. L. Coombes and F. Powrie, “Dendritic cells in intestinal immune regulation,” Nature Reviews Immunology, vol. 8, no. 6, pp. 435–446, 2008. View at: Publisher Site | Google Scholar
  83. C. M. Sun, J. A. Hall, R. B. Blank et al., “Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid,” Journal of Experimental Medicine, vol. 204, no. 8, pp. 1775–1785, 2007. View at: Publisher Site | Google Scholar
  84. S. Uematsu, K. Fujimoto, M. H. Jang et al., “Regulation of humoral and cellular gut immunity by lamina propria dendritic cells expressing Toll-like receptor 5,” Nature Immunology, vol. 9, no. 7, pp. 769–776, 2008. View at: Publisher Site | Google Scholar
  85. T. L. Denning, B. A. Norris, O. Medina-Contreras et al., “Functional specializations of intestinal dendritic cell and macrophage subsets that control Th17 and regulatory T cell responses are dependent on the T cell/APC ratio, source of mouse strain, and regional localization,” The Journal of Immunology, vol. 187, no. 2, pp. 733–747, 2011. View at: Publisher Site | Google Scholar
  86. O. Takeuchi and S. Akira, “Pattern recognition receptors and inflammation,” Cell, vol. 140, no. 6, pp. 805–820, 2010. View at: Publisher Site | Google Scholar
  87. M. Dalod, R. Chelbi, B. Malissen, and T. Lawrence, “Dendritic cell maturation: functional specialization through signaling specificity and transcriptional programming,” The EMBO Journal, vol. 33, no. 10, pp. 1104–1116, 2014. View at: Publisher Site | Google Scholar
  88. D. Han, M. C. Walsh, P. J. Cejas et al., “Dendritic cell expression of the signaling molecule TRAF6 is critical for gut microbiota-dependent immune tolerance,” Immunity, vol. 38, no. 6, pp. 1211–1222, 2013. View at: Publisher Site | Google Scholar
  89. X. Chen and J. J. Oppenheim, “Th17 cells and Tregs: unlikely allies,” Journal of Leukocyte Biology, vol. 95, no. 5, pp. 723–731, 2014. View at: Publisher Site | Google Scholar
  90. G. Reid, J. A. Younes, H. C. van der Mei, G. B. Gloor, R. Knight, and H. J. Busscher, “Microbiota restoration: natural and supplemented recovery of human microbial communities,” Nature Reviews Microbiology, vol. 9, no. 1, pp. 27–38, 2011. View at: Publisher Site | Google Scholar
  91. T. D. Leser and L. Mølbak, “Better living through microbial action: the benefits of the mammalian gastrointestinal microbiota on the host,” Environmental Microbiology, vol. 11, no. 9, pp. 2194–2206, 2009. View at: Publisher Site | Google Scholar
  92. S. K. Mazmanian, C. H. Liu, A. O. Tzianabos, and D. L. Kasper, “An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system,” Cell, vol. 122, no. 1, pp. 107–118, 2005. View at: Publisher Site | Google Scholar
  93. W. S. Garrett, J. I. Gordon, and L. H. Glimcher, “Homeostasis and inflammation in the intestine,” Cell, vol. 140, no. 6, pp. 859–870, 2010. View at: Publisher Site | Google Scholar
  94. I. I. Ivanov and K. Honda, “Intestinal commensal microbes as immune modulators,” Cell Host and Microbe, vol. 12, no. 4, pp. 496–508, 2012. View at: Publisher Site | Google Scholar
  95. S. K. Mazmanian, J. L. Round, and D. L. Kasper, “A microbial symbiosis factor prevents intestinal inflammatory disease,” Nature, vol. 453, no. 7195, pp. 620–625, 2008. View at: Publisher Site | Google Scholar
  96. B. Ruiz-Perez, D. R. Chung, A. H. Sharpe et al., “Modulation of surgical fibrosis by microbial zwitterionic polysaccharides,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 46, pp. 16753–16758, 2005. View at: Publisher Site | Google Scholar
  97. L. L. Presley, B. Wei, J. Braun, and J. Borneman, “Bacteria associated with immunoregulatory cells in mice,” Environmental Microbiology, vol. 76, no. 3, pp. 936–941, 2010. View at: Publisher Site | Google Scholar
  98. K. Pokusaeva, G. F. Fitzgerald, and D. van Sinderen, “Carbohydrate metabolism in bifidobacteria,” Genes & Nutrition, vol. 6, no. 3, pp. 285–306, 2011. View at: Publisher Site | Google Scholar
  99. M. Blaut, “Relationship of prebiotics and food to intestinal microflora,” European Journal of Nutrition, vol. 41, no. 1, pp. 11–16, 2002. View at: Google Scholar
  100. A. Barcelo, J. Claustre, F. Moro, J.-A. Chayvialle, J.-C. Cuber, and P. Plaisancié, “Mucin secretion is modulated by luminal factors in the isolated vascularly perfused rat colon,” Gut, vol. 46, no. 2, pp. 218–224, 2000. View at: Publisher Site | Google Scholar
  101. A. J. Brown, S. M. Goldsworthy, A. A. Barnes et al., “The orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids,” The Journal of Biological Chemistry, vol. 278, no. 13, pp. 11312–11319, 2003. View at: Publisher Site | Google Scholar
  102. E. Le Poul, C. Loison, S. Struyf et al., “Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation,” The Journal of Biological Chemistry, vol. 278, no. 28, pp. 25481–25489, 2003. View at: Publisher Site | Google Scholar
  103. N. E. Nilsson, K. Kotarsky, C. Owman, and B. Olde, “Identification of a free fatty acid receptor, FFA2R, expressed on leukocytes and activated by short-chain fatty acids,” Biochemical and Biophysical Research Communications, vol. 303, no. 4, pp. 1047–1052, 2003. View at: Publisher Site | Google Scholar
  104. D. K. Covington, C. A. Briscoe, A. J. Brown, and C. K. Jayawickreme, “The G-protein-coupled receptor 40 family (GPR40-GPR43) and its role in nutrient sensing,” Biochemical Society Transactions, vol. 34, no. 5, pp. 770–773, 2006. View at: Publisher Site | Google Scholar
  105. K. M. Maslowski, A. T. Vieira, A. Ng et al., “Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43,” Nature, vol. 461, no. 7268, pp. 1282–1286, 2009. View at: Publisher Site | Google Scholar
  106. M. A. R. Vinolo, H. G. Rodrigues, E. Hatanaka, C. B. Hebeda, S. H. P. Farsky, and R. Curi, “Short-chain fatty acids stimulate the migration of neutrophils to inflammatory sites,” Clinical Science (Lond), vol. 117, no. 9, pp. 331–338, 2009. View at: Publisher Site | Google Scholar
  107. J.-S. Park, E.-J. Lee, J.-C. Lee, W.-K. Kim, and H.-S. Kim, “Anti-inflammatory effects of short chain fatty acids in IFN-γ-stimulated RAW 264.7 murine macrophage cells: involvement of NF-κB and ERK signaling pathways,” International Immunopharmacology, vol. 7, no. 1, pp. 70–77, 2007. View at: Publisher Site | Google Scholar
  108. M. A. R. Vinolo, H. G. Rodrigues, E. Hatanaka, F. T. Sato, S. C. Sampaio, and R. Curi, “Suppressive effect of short-chain fatty acids on production of proinflammatory mediators by neutrophils,” Journal of Nutritional Biochemistry, vol. 22, no. 9, pp. 849–855, 2011. View at: Publisher Site | Google Scholar
  109. D. J. A. Jenkins, C. W. C. Kendall, and V. Vuksan, “Inulin, oligofructose and intestinal function,” Journal of Nutrition, vol. 129, no. 7, pp. 1431S–1433S, 1999. View at: Google Scholar
  110. Y. Sanz, I. Nadal, and E. Sánchez, “Probiotics as drugs against human gastrointestinal infections,” Recent Patents on Anti-Infective Drug Discovery, vol. 2, no. 2, pp. 148–156, 2007. View at: Publisher Site | Google Scholar
  111. L. Vogt, U. Ramasamy, D. Meyer et al., “Immune modulation by different types of beta21-fructans is toll-like receptor dependent,” PLoS ONE, vol. 8, no. 7, Article ID e68367, 2013. View at: Publisher Site | 1-fructans%20is%20toll-like%20receptor%20dependent&author=L. Vogt&author=U. Ramasamy&author=D. Meyer et al.&publication_year=2013" target="_blank">Google Scholar
  112. L. M. Vogt, D. Meyer, G. Pullens et al., “Toll-like receptor 2 activation by β21-fructans protects barrier function of T84 human intestinal epithelial cells in a chain length-dependent manner,” Journal of Nutrition, vol. 144, no. 7, pp. 1002–1008, 2014. View at: Publisher Site | 1-fructans%20protects%20barrier%20function%20of%20T84%20human%20intestinal%20epithelial%20cells%20in%20a%20chain%20length-dependent%20manner&author=L. M. Vogt&author=D. Meyer&author=G. Pullens et al.&publication_year=2014" target="_blank">Google Scholar
  113. N. R. Ryz, J. B. Meddings, and C. G. Taylor, “Long-chain inulin increases dendritic cells in the Peyer's patches and increases ex vivo cytokine secretion in the spleen and mesenteric lymph nodes of growing female rats, independent of zinc status,” British Journal of Nutrition, vol. 101, no. 11, pp. 1653–1663, 2009. View at: Publisher Site | Google Scholar
  114. J. Herre, S. Gordon, and G. D. Brown, “Dectin-1 and its role in the recognition of β-glucans by macrophages,” Molecular Immunology, vol. 40, no. 12, pp. 869–876, 2004. View at: Publisher Site | Google Scholar
  115. M. E. Taylor, J. T. Conary, M. R. Lennartz, P. D. Stahl, and K. Drickamer, “Primary structure of the mannose receptor contains multiple motifs resembling carbohydrate-recognition domains,” The Journal of Biological Chemistry, vol. 265, no. 21, pp. 12156–12162, 1990. View at: Google Scholar
  116. A. C. Ouwehand, M. Derrien, W. de Vos, K. Tiihonen, and N. Rautonen, “Prebiotics and other microbial substrates for gut functionality,” Current Opinion in Biotechnology, vol. 16, no. 2, pp. 212–217, 2005. View at: Publisher Site | Google Scholar
  117. J. H. Cummings, G. T. Macfarlane, and H. N. Englyst, “Prebiotic digestion and fermentation,” The American Journal of Clinical Nutrition, vol. 73, no. 2, supplement, pp. 415S–420S, 2001. View at: Google Scholar
  118. H. R. Gaskins, R. I. Mackie, T. May, and K. A. Garleb, “Dietary fructo-oligosaccharide modulates large intestinal inflammatory responses to Clostridium difficile in antibiotic-compromised mice,” Microbial Ecology in Health & Disease, vol. 9, no. 4, pp. 157–166, 1996. View at: Publisher Site | Google Scholar
  119. C. J. Field, M. I. McBurney, S. Massimino, M. G. Hayek, and G. D. Sunvold, “The fermentable fiber content of the diet alters the function and composition of canine gut associated lymphoid tissue,” Veterinary Immunology and Immunopathology, vol. 72, no. 3-4, pp. 325–341, 1999. View at: Publisher Site | Google Scholar
  120. A. Letellier, S. Messier, L. Lessard, S. Chénier, and S. Quessy, “Host response to various treatments to reduce salmonella infections in swine,” Canadian Journal of Veterinary Research, vol. 65, no. 3, pp. 168–172, 2001. View at: Google Scholar
  121. R. Herich, V. Révajová, M. Levkut et al., “The effect of Lactobacillus paracasei and Raftilose P95 upon the non-specific immune response of piglets,” Food and Agricultural Immunology, vol. 14, pp. 171–179, 2002. View at: Google Scholar
  122. K. S. Swanson, C. M. Grieshop, E. A. Flickinger et al., “Supplemental fructooligosaccharides and mannanoligosaccharides influence immune function, ileal and total tract nutrient digestibilities, microbial populations and concentrations of protein catabolites in the large bowel of dogs,” Journal of Nutrition, vol. 132, no. 5, pp. 980–989, 2002. View at: Google Scholar
  123. K. S. Swanson, C. M. Grieshop, E. A. Flickinger et al., “Effects of supplemental fructooligosaccharides plus mannanoligosaccharides on immune function and ileal and fecal microbial populations in adult dogs,” Archiv für Tierernährung, vol. 56, no. 4, pp. 309–318, 2002. View at: Publisher Site | Google Scholar
  124. H. Qiao, L. C. Duffy, E. Griffiths et al., “Immune responses in rhesus rotavirus-challenged Balb/c mice treated with bifidobacteria and prebiotic supplements,” Pediatric Research, vol. 51, no. 6, pp. 750–755, 2002. View at: Publisher Site | Google Scholar
  125. D. Bunout, S. Hirsch, M. P. de la Maza et al., “Effects of prebiotics on the immune response to vaccination in the elderly,” Journal of Parenteral and Enteral Nutrition, vol. 26, no. 6, pp. 372–376, 2002. View at: Publisher Site | Google Scholar
  126. Y. Guigoz, F. Rochat, G. Perruisseau-Carrier, I. Rochat, and E. J. Schiffrin, “Effects of oligosaccharide on the faecal flora and non-specific immune system in elderly people,” Nutrition Research, vol. 22, no. 1-2, pp. 13–25, 2002. View at: Publisher Site | Google Scholar
  127. A. Hosono, A. Ozawa, R. Kato et al., “Dietary fructooligosaccharides induce immunoregulation of intestinal IgA secretion by murine peyer's patch cells,” Bioscience, Biotechnology and Biochemistry, vol. 67, no. 4, pp. 758–764, 2003. View at: Publisher Site | Google Scholar
  128. K. A. Kelly-Quagliana, P. D. Nelson, and R. K. Buddington, “Dietary oligofructose and inulin modulate immune functions in mice,” Nutrition Research, vol. 23, no. 2, pp. 257–267, 2003. View at: Publisher Site | Google Scholar
  129. N. Manhart, A. Spittler, H. Bergmeister, M. Mittlböck, and E. Roth, “Influence of fructooligosaccharides on Peyer's patch lymphocyte numbers in healthy and endotoxemic mice,” Nutrition, vol. 19, no. 7-8, pp. 657–660, 2003. View at: Publisher Site | Google Scholar
  130. C. M. Grieshop, E. A. Flickinger, K. J. Bruce, A. R. Patil, G. L. Czarnecki-Maulden, and G. C. Fahey Jr., “Gastrointestinal and immunological responses of senior dogs to chicory and mannan-oligosaccharides,” Archives of Animal Nutrition, vol. 58, no. 6, pp. 483–493, 2004. View at: Publisher Site | Google Scholar
  131. Y. Nakamura, S. Nosaka, M. Suzuki et al., “Dietary fructooligosaccharides up-regulate immunoglobulin A response and polymeric immunoglobulin receptor expression in intestines of infant mice,” Clinical & Experimental Immunology, vol. 137, no. 1, pp. 52–58, 2004. View at: Publisher Site | Google Scholar
  132. M. Roller, G. Rechkemmer, and B. Watzl, “Prebiotic Inulin Enriched with Oligofructose in Combination with the Probiotics Lactobacillus rhamnosus and Bifidobacterium lactis modulates intestinal immune Functions in Rats,” Journal of Nutrition, vol. 134, no. 1, pp. 153–156, 2004. View at: Google Scholar
  133. D. Bunout, G. Barrera, S. Hirsch et al., “Effects of a nutritional supplement on the immune response and cytokine production in free-living Chilean elderly,” Journal of Parenteral and Enteral Nutrition, vol. 28, no. 5, pp. 348–354, 2004. View at: Publisher Site | Google Scholar
  134. B. Langkamp-Henken, B. S. Bender, E. M. Gardner et al., “Nutritional formula enhanced immune function and reduced days of symptoms of upper respiratory tract infection in seniors,” Journal of the American Geriatrics Society, vol. 52, no. 1, pp. 3–12, 2004. View at: Publisher Site | Google Scholar
  135. E. N. Trushina, E. A. Martynova, D. B. Nikityk, O. K. Mustafina, and E. K. Baygarin, “The influence of dietary inulin and oligofructose on the cell-mediated and humoral immunity in rats,” Voprosy Pitaniia, vol. 74, no. 3, pp. 22–27, 2005. View at: Google Scholar
  136. A. M. Bakker-Zierikzee, E. A. F. van Tol, H. Kroes, M. S. Alles, F. J. Kok, and J. G. Bindels, “Faecal SIgA secretion in infants fed on pre- or pro-biotic infant formula,” Pediatric Allergy and Immunology, vol. 17, no. 2, pp. 134–140, 2006. View at: Publisher Site | Google Scholar
  137. B. Langkamp-Henken, S. M. Wood, K. A. Herlinger-Garcia et al., “Nutritional formula improved immune profiles of seniors living in nursing homes,” Journal of the American Geriatrics Society, vol. 54, no. 12, pp. 1861–1870, 2006. View at: Publisher Site | Google Scholar
  138. V. Adogony, F. Respondek, V. Biourge et al., “Effects of dietary scFOS on immunoglobulins in colostrums and milk of bitches,” Journal of Animal Physiology and Animal Nutrition, vol. 91, no. 5-6, pp. 169–174, 2007. View at: Publisher Site | Google Scholar
  139. C. J. Apanavicius, K. L. Powell, B. M. Vester et al., “Fructan supplementation and infection affect food intake, fever, and epithelial sloughing from salmonella challenge in weanling puppies,” Journal of Nutrition, vol. 137, no. 8, pp. 1923–1930, 2007. View at: Google Scholar
  140. C. Seidel, V. Boehm, H. Vogelsang et al., “Influence of prebiotics and antioxidants in bread on the immune system, antioxidative status and antioxidative capacity in male smokers and non-smokers,” British Journal of Nutrition, vol. 97, no. 2, pp. 349–356, 2007. View at: Publisher Site | Google Scholar
  141. J. Benyacoub, F. Rochat, K.-Y. Saudan et al., “Feeding a diet containing a fructooligosaccharide mix can enhance Salmonella vaccine efficacy in mice,” Journal of Nutrition, vol. 138, no. 1, pp. 123–129, 2008. View at: Google Scholar
  142. P. A. M. J. Scholtens, P. Alliet, M. Raes et al., “Fecal secretory immunoglobulin A is increased in healthy infants who receive a formula with short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides,” Journal of Nutrition, vol. 138, no. 6, pp. 1141–1147, 2008. View at: Google Scholar
  143. J. Vulevic, A. Drakoularakou, P. Yaqoob, G. Tzortzis, and G. R. Gibson, “Modulation of the fecal microflora profile and immune function by a novel trans-galactooligosaccharide mixture (B-GOS) in healthy elderly volunteers,” The American Journal of Clinical Nutrition, vol. 88, no. 5, pp. 1438–1446, 2008. View at: Publisher Site | Google Scholar
  144. E. van Hoffen, B. Ruiter, J. Faber et al., “A specific mixture of short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides induces a beneficial immunoglobulin profile in infants at high risk for allergy,” Allergy, vol. 64, no. 3, pp. 484–487, 2009. View at: Publisher Site | Google Scholar
  145. Y. Li, Y. Zong, J. Qi, and K. Liu, “Prebiotics and oxidative stress in constipated rats,” Journal of Pediatric Gastroenterology and Nutrition, vol. 53, no. 4, pp. 447–452, 2011. View at: Publisher Site | Google Scholar
  146. G. T. Choque Delgado, R. Thomé, D. L. Gabriel, W. M. S. C. Tamashiro, and G. M. Pastore, “Yacon (Smallanthus sonchifolius)-derived fructooligosaccharides improves the immune parameters in the mouse,” Nutrition Research, vol. 32, no. 11, pp. 884–892, 2012. View at: Publisher Site | Google Scholar
  147. J.-M. Lecerf, F. Dépeint, E. Clerc et al., “Xylo-oligosaccharide (XOS) in combination with inulin modulates both the intestinal environment and immune status in healthy subjects, while XOS alone only shows prebiotic properties,” British Journal of Nutrition, vol. 108, no. 10, pp. 1847–1858, 2012. View at: Publisher Site | Google Scholar
  148. J. Vulevic, A. Juric, G. Tzortzis, and G. R. Gibson, “A mixture of trans-galactooligosaccharides reduces markers of metabolic syndrome and modulates the fecal microbiota and immune function of overweight adults1-3,” The Journal of Nutrition, vol. 143, no. 3, pp. 324–331, 2013. View at: Publisher Site | Google Scholar
  149. G. Bouchaud, L. Castan, J. Chabauty, P. Aubert, M. Neunlist, and M. Bodinier, “11: perinatal exposure to galactooligosaccharides/inulin prebiotics prevent food allergy by protecting intestine and promoting tolerance,” Cytokine, vol. 70, no. 1, 30 pages, 2014. View at: Publisher Site | Google Scholar
  150. C. E. Childs, H. Röytiö, E. Alhoniemi et al., “Xylo-oligosaccharides alone or in synbiotic combination with Bifidobacterium animalis subsp. lactis induce bifidogenesis and modulate markers of immune function in healthy adults: a double-blind, placebo-controlled, randomised, factorial cross-over study,” British Journal of Nutrition, vol. 111, no. 11, pp. 1945–1956, 2014. View at: Publisher Site | Google Scholar
  151. L. Samal, V. B. Chaturvedi, G. Saikumar, R. Somvanshi, and A. K. Pattanaik, “Prebiotic potential of Jerusalem artichoke (Helianthus tuberosus L.) in Wistar rats: effects of levels of supplementation on hindgut fermentation, intestinal morphology, blood metabolites and immune response,” Journal of the Science of Food and Agriculture, 2014. View at: Publisher Site | Google Scholar
  152. A. Huazano-García and M. G. López, “Metabolism of short chain fatty acids in colon and faeces of mice after a supplementation of diets with agave fructans,” in Lipid Metabolism, R. Valenzuela Baez, Ed., vol. 8, pp. 163–182, InTech, Rijeka, Croatia, 2013. View at: Publisher Site | Google Scholar
  153. S. K. Chen, M. L. Tsai, J. R. Huang, and R. H. Chen, “In vitro antioxidant activities of low-molecular-weight polysaccharides with various functional groups,” Journal of Agricultural and Food Chemistry, vol. 57, no. 7, pp. 2699–2704, 2009. View at: Publisher Site | Google Scholar
  154. E. Hernandez-Marin and A. Martínez, “Carbohydrates and their free radical scavenging capability: a theoretical study,” Journal of Physical Chemistry B, vol. 116, no. 32, pp. 9668–9675, 2012. View at: Publisher Site | Google Scholar
  155. E. Keunen, D. Peshev, J. Vangronsveld, W. van den Ende, and A. Cuypers, “Plant sugars are crucial players in the oxidative challenge during abiotic stress: extending the traditional concept,” Plant, Cell and Environment, vol. 36, no. 7, pp. 1242–1255, 2013. View at: Publisher Site | Google Scholar
  156. W. Van den Ende and D. Peshev, “Sugars as antioxidants in plants,” in Crop Improvement Under Adverse Conditions, N. Tuteja and S. S. Gill, Eds., pp. 285–307, Springer, New York, NY, USA, 2013. View at: Publisher Site | Google Scholar
  157. D. Peshev, R. Vergauwen, A. Moglia, É. Hideg, and W. Van den Ende, “Towards understanding vacuolar antioxidant mechanisms: a role for fructans?” Journal of Experimental Botany, vol. 64, no. 4, pp. 1025–1038, 2013. View at: Publisher Site | Google Scholar
  158. C. H. Foyer, M. Lelandais, and K. J. Kunert, “Photooxidative stress in plants,” Physiologia Plantarum, vol. 92, no. 4, pp. 696–717, 1994. View at: Google Scholar
  159. A. Nishizawa, Y. Yabuta, and S. Shigeoka, “Galactinol and raffinose constitute a novel function to protect plants from oxidative damage,” Plant Physiology, vol. 147, no. 3, pp. 1251–1263, 2008. View at: Publisher Site | Google Scholar
  160. S. Stoyanova, J. Geuns, É. Hideg, and W. Van den Ende, “The food additives inulin and stevioside counteract oxidative stress,” International Journal of Food Sciences and Nutrition, vol. 62, no. 3, pp. 207–214, 2011. View at: Publisher Site | Google Scholar
  161. X. M. Li, Y. H. Shi, F. Wang, H. S. Wang, and G. W. Le, “In vitro free radical scavenging activities and effect of synthetic oligosaccharides on antioxidant enzymes and lipid peroxidation in aged mice,” Journal of Pharmaceutical and Biomedical Analysis, vol. 43, no. 1, pp. 364–370, 2007. View at: Publisher Site | Google Scholar
  162. M. Glei, T. Hofmann, K. Küster, J. Hollmann, M. G. Lindhauer, and B. L. Pool-Zobel, “Both wheat (Triticum aestivum) bran arabinoxylans and gut flora-mediated fermentation products protect human colon cells from genotoxic activities of 4-hydroxynonenal and hydrogen peroxide,” Journal of Agricultural and Food Chemistry, vol. 54, no. 6, pp. 2088–2095, 2006. View at: Publisher Site | Google Scholar
  163. J. Juśkiewicz, Z. Zduńczyk, E. Zary-Sikorska, B. Król, J. Milala, and A. Jurgoński, “Effect of the dietary polyphenolic fraction of chicory root, peel, seed and leaf extracts on caecal fermentation and blood parameters in rats fed diets containing prebiotic fructans,” British Journal of Nutrition, vol. 105, no. 5, pp. 710–720, 2011. View at: Publisher Site | Google Scholar

Copyright © 2015 Elena Franco-Robles and Mercedes G. López. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

3997 Views | 1286 Downloads | 35 Citations
 PDF  Download Citation  Citation
 Download other formatsMore
 Order printed copiesOrder