Fructose-Containing Plant Carbohydrates: Biological Activities and Medical Applications.

The review considers the chemical structure specifics and distribution in plants for fructose-containing carbohydrates (fructans). Various biological activities were observed in fructans and associated with their physicochemical features. Fructans affect many physiological and biochemical processes in the human body, improving health and reducing the risk of various disorders. Prebiotic activity is the most important physiological function of fructans. Fructans improve the microflora composition in the colon and intestinal mucosa by increasing the content of useful bacteria and decreasing the content of potentially harmful microorganisms, stimulate the physiological functions of the microflora, and provide for a better state of the intestine and a better health status. By modifying the intestinal microbiota and utilizing certain additional mechanisms, fructans can favorably affect the immune function, decrease the risk of various inflammatory processes, and to reduce the likelihood of tumorigenesis due to exposure to carcinogens. Fructans improve carbohydrate and lipid metabolism by reducing the blood levels of glucose, total cholesterol, low-density lipoprotein (LDL), and very-low-density lipoprotein (VLDL) and increasing the blood content of high-density lipoprotein (HLD). Fructans are low in calories, and their use in foods reduces the risk of obesity. Fructans facilitate higher calcium absorption and increase the bone density, thus reducing the risk of osteoporosis. Fructants protect the body from oxidative stress, intestinal infections, and parasitic invasions.

Effect of moringa leaf powder and agave inulin on performance, intestinal morphology, and meat yield of broiler chickens.

The addition prebiotics in broiler diets can benefit digestion and nutrient abortion. The objective of the present study was to evaluate the effects of moringa leaf powder and agave inulin on growth performance, intestinal morphology, and slaughter traits of broiler chickens over 40 d of grow-out. A total of 280 broilers (Ross 308) aged 1 d were randomly allocated to 4 treatments, with 7 replicates each and 10 chicks per replicate: T1 = control diet, T2 = control diet with 15 g/kg of moringa leaf powder, T3 = control diet with 15 g/kg of agave inulin, and T4 = control diet with 15 g/kg of moringa leaf powder and 15 g/kg of agave inulin. The results showed that analysis of treatments at time were not different (P > 0.05) for broiler weights, feed and water intake, and weight gain. Treatment was significant (P < 0.05) for feed efficiency at 22 to 40 d; the T4 group presented higher (P < 0.05) values, and the T1 group presented lower (P < 0.05) values. However, the villus lengths of intestinal sections were different (P < 0.05) among treatments. In the duodenum, jejunum, and ileum, villus lengths were highest (P < 0.05) in the T2 group and lowest (P < 0.05) in the T3 and T4 groups. Villus widths in the duodenum and ileum were highest (P < 0.05) in the T2 group, but the T1 group showed highest (P < 0.05) values in the jejunum sections. The T3 and T4 groups showed lowest (P < 0.05) values in villus width in the duodenum, jejunum, and ileum. Thigh yield was highest (P < 0.05) in the T2 group and lowest (P < 0.05) in the T4 group. The T1 group exhibited the highest (P < 0.05) piece yields for leg, wing, and hip-back. The T4 group showed lowest (P < 0.05) leg and wing yields. Moringa leaf powder and agave inulin at a concentration of 15 g/kg in diets did not affect broiler performance, whereas moringa leaf powder improved intestinal morphology and thigh yield, and agave inulin improved leg yield. The results demonstrated benefits of these 2 feed additives to improve intestine health and meat yield in broilers over a 40-day grow-out.

Osteopontin Affects Insulin Vesicle Localization and Ca2+ Homeostasis in Pancreatic Beta Cells from Female Mice.

Type 2 diabetic patients suffer from insulin resistance and reduced insulin secretion. Osteopontin (OPN), a versatile protein expressed in several tissues throughout the body including the islets of Langerhans, has previously been implicated in the development of insulin resistance. Here we have investigated the role of OPN in insulin secretion using an OPN knock out mouse model (OPN-/-). Ultra-structural analyzes of islets from OPN-/- and WT mice indicated weaker cell-cell connections between the islet cells in the OPN-/- mouse compared to WT. Analysis of the insulin granule distribution in the beta cells showed that although OPN-/- and WT beta cells have the same number of insulin granules OPN-/- beta cells have significantly fewer docked granules. Both OPN-/- and WT islets displayed synchronized Ca2+ oscillations indicative of an intact beta cell communication. OPN-/- islets displayed higher intracellular Ca2+ concentrations when stimulated with 16.7 mM glucose than WT islets and the initial dip upon elevated glucose concentrations (which is associated with Ca2+ uptake into ER) was significantly lower in these islets. Glucose-induced insulin secretion was similar in OPN-/- and WT islets. Likewise, non-fasted blood glucose levels were the same in both groups. In summary, deletion of OPN results in several minor beta-cell defects that can be compensated for in a healthy system.

The prebiotic inulin as a functional food - a review.

The newborn digestive tract is rapidly colonized right after birth. The type of feeding could significantly influence this colonization process. Infant formulas like inulin try to mimic the bifidogenic effects of human milk by addition of prebiotics. Moreover, studies in the recent past have evidenced important effects of inulin during early infant life. The present review article will highlight recent updates about the use of inulin in the pediatric clinical setting.

Safety and immunogenicity of a delta inulin-adjuvanted inactivated Japanese encephalitis virus vaccine in pregnant mares and foals.

In 2011, following severe flooding in Eastern Australia, an unprecedented epidemic of equine encephalitis occurred in South-Eastern Australia, caused by Murray Valley encephalitis virus (MVEV) and a new variant strain of Kunjin virus, a subtype of West Nile virus (WNVKUN). This prompted us to assess whether a delta inulin-adjuvanted, inactivated cell culture-derived Japanese encephalitis virus (JEV) vaccine (JE-ADVAX™) could be used in horses, including pregnant mares and foals, to not only induce immunity to JEV, but also elicit cross-protective antibodies against MVEV and WNVKUN. Foals, 74-152 days old, received two injections of JE-ADVAX™. The vaccine was safe and well-tolerated and induced a strong JEV-neutralizing antibody response in all foals. MVEV and WNVKUN antibody cross-reactivity was seen in 33% and 42% of the immunized foals, respectively. JE-ADVAX™ was also safe and well-tolerated in pregnant mares and induced high JEV-neutralizing titers. The neutralizing activity was passively transferred to their foals via colostrum. Foals that acquired passive immunity to JEV via maternal antibodies then were immunized with JE-ADVAX™ at 36-83 days of age, showed evidence of maternal antibody interference with low peak antibody titers post-immunization when compared to immunized foals of JEV-naïve dams. Nevertheless, when given a single JE-ADVAX™ booster immunization as yearlings, these animals developed a rapid and robust JEV-neutralizing antibody response, indicating that they were successfully primed to JEV when immunized as foals, despite the presence of maternal antibodies. Overall, JE-ADVAX™ appears safe and well-tolerated in pregnant mares and young foals and induces protective levels of JEV neutralizing antibodies with partial cross-neutralization of MVEV and WNVKUN.

ERK is involved in EGF-mediated protection of tight junctions, but not adherens junctions, in acetaldehyde-treated Caco-2 cell monolayers.

The role of mitogen-activated protein kinases (MAPK) in the mechanism of EGF-mediated prevention of acetaldehyde-induced tight junction disruption was evaluated in Caco-2 cell monolayers. Pretreatment of cell monolayers with EGF attenuated acetaldehyde-induced decrease in resistance and increase in inulin permeability and redistribution of occludin, zona occludens-1 (ZO-1), E-cadherin, and ß-catenin from the intercellular junctions. EGF rapidly increased the levels of phospho-ERK1/2, phospho-p38 MAPK, and phospho-JNK1. Pretreatment of cell monolayers with U-0126 (inhibitor of ERK activation), but not SB-202190 and SP-600125 (p38 MAPK and JNK inhibitors), significantly attenuated EGF-mediated prevention of acetaldehyde-induced changes in resistance, inulin permeability, and redistribution of occludin and ZO-1. U-0126, but not SB-202190 and SP-600125, also attenuated EGF-mediated prevention of acetaldehyde effect on the midregion F-actin ring. However, EGF-mediated preservation of junctional distribution of E-cadherin and ß-catenin was unaffected by all three inhibitors. Expression of wild-type or constitutively active MEK1 attenuated acetaldehyde-induced redistribution of occludin and ZO-1, whereas dominant-negative MEK1 prevented EGF-mediated preservation of occludin and ZO-1 in acetaldehyde-treated cells. MEK1 expression did not alter E-cadherin distribution in acetaldehyde-treated cells in the presence or absence of EGF. Furthermore, EGF attenuated acetaldehyde-induced tyrosine-phosphorylation of occludin, ZO-1, claudin-3, and E-cadherin. U-0126, but not SB-202190 and SP-600125, prevented EGF effect on tyrosine-phosphorylation of occludin and ZO-1, but not claudin-3, E-cadherin, or ß-catenin. These results indicate that EGF-mediated protection of tight junctions from acetaldehyde requires the activity of ERK1/2, but not p38 MAPK or JNK1/2, and that EGF-mediated protection of adherens junctions is independent of MAPK activities.

The bifidogenic effect of inulin and oligofructose and its consequences for gut health.

The bifidogenic effect of inulin and oligofructose is now well established in various studies, not only in adult participants but also in other age groups. This bifidogenic shift in the composition of the colonic microbiota is likely the basis for the impact of these prebiotic compounds on various parameters of colonic function. Mainly from animal and in vitro studies and also from some human trials, there are indications, for instance, that inulin-type fructans may reduce the production of potentially toxic metabolites and may induce important immune-mediated effects. This review discusses how these changes in the composition and activity of the colonic microbiota may affect gut health in healthy people, including in those who may experience some form of gastrointestinal discomfort.

Inulin-type fructans: functional food ingredients.

A food (ingredient) is regarded as functional if it is satisfactorily demonstrated to affect beneficially 1 or more target functions in the body beyond adequate nutritional effects. The term inulin-type fructans covers all beta(2<--1) linear fructans including native inulin (DP 2-60, DP(av) = 12), oligofructose (DP 2-8, DP(av) = 4), and inulin HP (DP 10-60, DP(av) = 25) as well as Synergy 1, a specific combination of oligofructose and inulin HP. Inulin-type fructans resist digestion and function as dietary fiber improving bowel habits. But, unlike most dietary fibers, their colonic fermentation is selective, thus causing significant changes in the composition of the gut microflora with increased and reduced numbers of potentially health-promoting bacteria and potentially harmful species, respectively. Both oligofructose and inulin act in this way and thus are prebiotic: they also induce changes in the colonic epithelium and in miscellaneous colonic functions. In particular, the claim "inulin-type fructans enhance calcium and magnesium absorption" is scientifically substantiated, and the most active product is oligofructose-enriched inulin (Synergy 1). A series of studies furthermore demonstrate that inulin-type fructans modulate the secretion of gastrointestinal peptides involved in appetite regulation as well as lipid metabolism. Moreover, a large number of animal studies and preliminary human data show that inulin-type fructans reduce the risk of colon carcinogenesis and improve the management of inflammatory bowel diseases. Inulin-type fructans are thus functional food ingredients that are eligible for enhanced function claims, but, as more human data become available, risk reduction claims will become scientifically substantiated.

Prebiotic capacity of inulin-type fructans.

The human gut microbiota plays a significant role in human health through its ability to digest food ingredients and manufacture metabolites. This can be positive or negative for host welfare. Moreover, the microflora plays an active role in host defense whereby colonization resistance affords protection against pathogens. Prebiotics are nondigestible food ingredients that target beneficial components of the gut microflora (mainly colonic), particularly the bifidobacteria. In vitro and in vivo evidence has accumulated to confirm the prebiotic effects of inulin-derived fructans.

Inulin and oligofructose and mineral metabolism: the evidence from animal trials.

Nondigestible oligosaccharides have been shown to increase the absorption of several minerals (calcium, magnesium, in some cases phosphorus) and trace elements (mainly copper, iron, zinc). Inulin-type fructans including oligofructose and fructooligosaccharides derived from sucrose by enzymatic transfructosylation are the best investigated food ingredients in this respect. The stimulation of absorption was more pronounced when the demand for calcium was high, i.e., in animals in the rapid growing stage and in animals with impaired calcium absorption because of either ovariectomy or gastrectomy. Even a small stimulation of calcium absorption increased the mineral accumulation in the skeleton because of its persisting effect over months. Inulin-type fructans stimulated mineral absorption and bone mineral accretion when combined with probiotic lactobacilli and in the presence of antibiotics. Direct comparison of different inulin-type fructans revealed a more pronounced effect by inulin or a mixture of long-chain inulin and oligofructose than by oligofructose alone. Mechanisms on how inulin-type fructans mediate this effect include acidification of the intestinal lumen by short-chain fatty acids increasing solubility of minerals in the gut, enlargement of the absorption surface, increased expression of calcium-binding proteins mainly in the large intestine, modulated expression of bone-relevant cytokines, suppression of bone resorption, increased bioavailability of phytoestrogens, and, via stimulation of beneficial commensal microorganisms, increase of calcium uptake by enterocytes. Under certain conditions, inulin-type fructans may improve mineral absorption by their impact on the amelioration of gut health including stabilization of the intestinal flora and reduction of inflammation. The abundance of reports indicate that inulin-type fructans are promising substances that could help to improve the supply with available calcium in human nutrition and by this contribute to bone health.

Current data with inulin-type fructans and calcium, targeting bone health in adults.

In humans, there is increasing evidence that the colon can absorb nutritionally significant amounts of calcium, and this process may be susceptible to dietary manipulation by fermentable substrates, especially inulin-type fructans. Inulin-type fructans can modulate calcium absorption because they are resistant to hydrolysis by mammalian enzymes and are fermented in the large intestine to produce short-chain fatty acids, which in turn reduce luminal pH and modify calcium speciation, and hence solubility, or exert a direct effect on the mucosal transport pathway. Quite a few intervention studies showed an improvement of calcium absorption in adolescents or young adults by inulin-type fructans. In the same way, a positive effect has been reported in older women.

Introducing inulin-type fructans.

Inulin is a generic term to cover all beta(2-->1) linear fructans. Chicory inulin is a linear beta(2-->1) fructan (degree of polymerisation (DP) 2 to 60; DPav=12), its partial enzymatic hydrolysis product is oligofructose (DP 2 to 8; DPav=4), and by applying specific separation technologies a long-chain inulin known as inulin HP (DP 10 to 60; DPav=25) can be produced. Finally, a specific product known as oligofructose-enriched inulin is obtained by combining chicory long-chain inulin and oligofructose. Because of the beta-configuration of the anomeric C2 in their fructose monomers, inulin-type fructans resist hydrolysis by intestinal digestive enzymes, they classify as 'non-digestible' carbohydrates, and they are dietary fibres. By increasing faecal biomass and water content of the stools, they improve bowel habits, but they have characteristic features different from other fibres. They affect gastrointestinal functions not because of their physico-chemical properties but rather because of their biochemical and physiological attributes. In the colon, they are rapidly fermented to produce SCFA that are good candidates to explain some of the systemic effects of inulin-type fructans. Fermentation of inulin-type fructans in the large bowel is a selective process; bifidobacteria (and possibly a few other genera) are preferentially stimulated to grow, thus causing significant changes in the composition of the gut microflora by increasing the number of potentially health-promoting bacteria and reducing the number of potentially harmful species. Both oligofructose and inulin are prebiotic. They also induce changes in colonic epithelium stimulating proliferation in the crypts, increasing the concentration of polyamines, changing the profile of mucins, and modulating endocrine as well as immune functions. From a nutrition labelling perspective, inulin-type fructans are not only prebiotic dietary fibres; they are also low-calorie carbohydrates [6.3 kJ/g (1.5 kcal/g)]. Supported by the results of a large number of animal studies and human nutrition intervention trials, the claim 'inulin-type fructans enhance calcium and magnesium absorption' is scientifically substantiated, but different inulin-type fructans have probably a different efficacy (in terms of effective daily dose), the most active product being the oligofructose-enriched inulin. A series of animal studies demonstrate that inulin-type fructans affect the metabolism of lipids primarily by decreasing triglyceridaemia because of a reduction in the number of plasma VLDL particles. The human data largely confirm the animal experiments. They demonstrate mainly a reduction in triglyceridaemia and only a relatively slight decrease in cholesterolaemia mostly in (slightly) hypertriglyceridaemic conditions. Inulin appears thus eligible for an enhanced function claim related to normalization of blood triacylglycerols. A large number of animal data convincingly show that inulin-type fructans reduce the risk of colon carcinogenesis and nutrition intervention trials are now performed to test that hypothesis in human subjects known to be at risk for polyps and cancer development in the large bowel.

Physiological effects of lactulose and inulin in the caecum of rats.

A model experiment was performed on rats to evaluate the effect of partial or total substitution of saccharose (S) and cellulose (C) by preparations of lactulose and inulin on the development and metabolism of the caecum. In the experimental diets given to rats for 4 weeks, the examined preparations were administered either with an equivalent amount of cellulose (each at 4% of the diet) or as sole source of dietary fibre at 8% of the diet. Compared to the saccharose group cellulose had no effect, and low doses of lactulose and inulin in the diet increased to a medium extent the weight of the caecum wall and caecal digesta. The addition of lactulose and inulin at 8% increased significantly the content of caecal digesta (4.62 and 4.11 g/100g BW, respectively) and the weight of the caecal wall (1.10 and 0.86 g/100g BW, respectively), compared to the groups with saccharose and cellulose (0.73, 0.90 and 0.24, 0.28 g/100g BW, respectively). Cellulose and cellulose partially-substituted with lactulose and inulin caused an increase in the dry matter content of caecal digesta (26.5-27.5%), compared to other groups (21.8-22.8%). The administration of lactulose and inulin preparations was accompanied by a significant drop in pH (5.47-5.81), compared to the groups with cellulose or saccharose (6.83-6.91), and a decrease in the ammonia concentration in the caecal digesta, compared to the cellulose control (0.27-0.40 and 0.62 mg/g, respectively). The group with 8% lactulose was characterized by the highest activities of microbiological alpha- and beta-galactosidase and beta-glucosidase in the caecal digesta. Cellulose and both preparations significantly decreased the activity of beta-glucuronidase, compared to the saccharose group (0.39-0.89 and 1.52 U/g, respectively). The highest concentration of VFA in the caecal digesta was observed in the saccharose group (89.2 micromol/g), and the lowest concentration in the group where cellulose was totally substituted by lactulose and inulin (55.1 and 57.5 micromol/g, respectively). The total production of VFA in the caecum was fourfold higher with 8 % lactulose and inulin (254.7 and 236.4 micromol/100g BW, respectively) than in both controls groups (65.1 and 67.8 micromol/100g BW, respectively). The high dose of inulin and lactulose increased the share of propionic acid in the VFA profile (C2:C3:C4) compared to both control groups. When 4% inulin was added to the diet a significant increase of butyrate concentration in the caecum was observed.

Inulin stimulates NO synthesis via activation of PKC-alpha and protein tyrosine kinase, resulting in the activation of NF-kappaB by IFN-gamma-primed RAW 264.7 cells.

Inulin, an active component of Chicorium intybus root, has been shown to stimulate the growth of bifidobacteria, and inhibit colon carcinogenesis. NO mediates a number of the host-defense functions of activated macrophages, including antimicrobial and tumoricidal activity. We examined the effect of inulin on the synthesis of NO in RAW 264.7 cells. Inulin alone had no effect, whereas inulin with IFN-gamma synergistically increased the NO production and inducible NO synthase (iNOS) expression in RAW 264.7 cells. Synergy between IFN-gamma and inulin was mainly dependent on inulin-induced TNF-alpha secretion. Also, protein kinase C (PKC)-alpha was involved in the inulin-induced NO production. Inulin-mediated NO production was inhibited by the protein tyrosine kinase (PTK) inhibitor, tyrphostin AG126. Since iNOS gene transcriptions have been shown to be under the control of the NF-kappaB/Rel family of transcription factors, we assessed the effect of inulin on NF-kappaB/Rel using an EMSA. Inulin produced strong induction of NF-kappaB/Rel binding, whereas AP-1 binding was slightly induced in RAW 264.7 cells. Inulin stimulated phosphorylation and degradation of IkappaB-alpha. These results suggest that in IFN-gamma-primed RAW 264.7 cells inulin might stimulate NO synthesis via activation of PKC-alpha and PTK, resulting in the activation of NF-kappaB.

The adverse renal effects of prostaglandin-synthesis inhibitors in the newborn rabbit.

Nonsteroidal anti-inflammatory drugs are frequently used during pregnancy (premature labor, polyhydramnios) and the immediate postnatal period (closure of patent ductus arteriosus). This article evaluates the renal effect of 3 nonspecific COX inhibitors (aspirin, indomethacin, and ibuprofen) in newborn rabbits. Five groups of anesthetized, ventilated, normoxemic 6-day-old rabbits (n = 52) were administered intravenous aspirin (40 mg/kg), indomethacin (2 mg/kg), and ibuprofen (0.02, 0.2, 2.0 mg/kg, respectively). Renal function and hemodynamics as assessed by inulin and para-aminohippuric acid clearances were measured before and in the hour after drug administration. In all groups of animals, the nonselective COX inhibitors induced an increase in renal vascular resistance and a consequent decrease in glomerular filtration rate and renal blood flow. Urine flow rate decreased significantly in all groups, except in the group receiving the lowest dose of ibuprofen. In newborn rabbits, aspirin, indomethacin, and ibuprofen induced intense renal vasoconstriction, which resulted in impaired renal function. This observation illustrates the major renal protective role played by the vasodilatory prostaglandins during the neonatal period, when the kidney is perfused at very low perfusion pressure. We conclude that all COX inhibitors should be administered with the same caution to the preterm neonate.

Concepts in functional foods: the case of inulin and oligofructose.

Recent advances in biosciences support the hypothesis that diet modulates various body functions. Diet may maintain well-being and reduce the risk of some diseases. Such discoveries have led to the concept of "functional food" and the development of the new discipline, i.e., "functional food science." A practical and simple definition of a "functional food" is a food for which a claim has been authorized. The food components to be discussed as potential "functional food ingredients" are the inulin-type fructans, i.e., chicory inulin and oligofuctose. The targets for their effects are the colonic microflora, the gastrointestinal physiology, the immune functions, the bioavailability of minerals, the metabolism of lipids and colonic carcinogenesis. Potential health benefits include reduction of risk of colonic diseases, noninsulin-dependent diabetes, obesity, osteoporosis and cancer. The documentation of such benefits requires scientific evidence that must be evaluated in terms of "health claims." Previous assessments have concluded that, in terms of "functional claims," strong evidence exists for a prebiotic effect and improved bowel habit. The evidence for calcium bioavailability is promising, and positive modulation of triglyceride metabolism is undergoing preliminary evaluation. Scientific research still must be done to support any "disease risk reduction claim," but sound hypotheses do already exist for designing the relevant human nutrition trials.

Inulin and oligofructose: what are they?

Inulin is a term applied to a heterogeneous blend of fructose polymers found widely distributed in nature as plant storage carbohydrates. Oligofructose is a subgroup of inulin, consisting of polymers with a degree of polymerization (DP)

Fiber, inulin and oligofructose: similarities and differences.

The biological, chemical and physical properties of dietary fibers are associated with physiologic actions in the small and large intestine that have important metabolic implications for health. These properties of fiber include dispersibility in water, bulk, viscosity, adsorption and binding of compounds and fermentability. Dietary fructans share some of the properties of dietary fiber and thus are likely to have similar metabolic effects. Within the small intestine, properties such as dispersibility in water, bulking and viscosity are associated with slowing the digestion and absorption of carbohydrate and lipid and promoting nutrient absorption along a greater length of the small intestine. Both of these actions are related to cholesterol reduction and blunting of alimentary gylcemia. Although fructans are dispersible in water and will provide some bulk because they are nondigestible in the small intestine, they do not appear to be associated with significant increases in viscosity. Thus one would predict that any immediate effects on alimentary glycemia or on cholesterol reduction are likely to be modest compared with more viscous polysaccharides. Fermentability and bulking capacity of nondigestible carbohydrates define an essential role of fiber in maintaining gastrointestinal health. Within the large intestine, carbohydrates that are not digested in the small intestine are available for fermentation by the microflora present. Carbohydrates that are dispersible in the aqueous phase are more readily digested by microbes. A large body of evidence indicates that dietary fructans are digested in the large intestine, resulting in an increase in microbial mass and production of short-chain fatty acids.