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Chemical modification of inulin, a valuable renewable resource, and its industrial applications.

Inulin, the polydisperse reserve polyfructose from plants such as Cichorium intybus (chicory), has been chemically modified in several ways to obtain industrially important biodegradable compounds. This review provides an insight on the different types of modification (neutral, anionic, and cationic modification as well as cross-linking and slow release applications) and describes its differences from starch and cellulose chemistry. It also highlights the applications of various compounds cited in the literature.

Absorbable Implants↗

Kinetics of formation of Di-D-fructose dianhydrides during thermal treatment of inulin.

Thermal treatments of solid mixtures of inulin and citric acid result in the formation of di-D-fructose dianhydrides and oligomers derived therefrom. The kinetics of formation of these compounds have been investigated and simulated in computer studies. A mechanism is proposed. The conditions used in this study were analogous to the conditions pertaining to the roasting of chicory, during which similar compounds are formed.

Anhydrides↗

Chemical syntheses of inulin and levan structures.

A fructofuranosyl thiglycoside donor, ethyl 6-O-acetyl-3-O-benzyl-1,4-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-2-thio-beta-D-fructofuranoside (11), designed to yield stereospecifically beta-linkages and also to allow subsequent elongation in the 6- and/or 1-positions, was prepared and used in syntheses of levan and inulin structures. DMTST-promoted glycosylation between 11 (1.3 mol equiv) and methyl beta-D-fructofuranoside 6-OH and 1-OH acceptors (3 and 6) gave stereospecifically the protected methyl levanobioside 12 and inulinobioside 17 in excellent yields (80 and 86%), respectively. Protecting group manipulations on these afforded new disaccharide 6'-OH and 1'-OH acceptors (13 and 19), which were coupled again with donor 11 (1.0 mol equiv) to yield methyl levanotrioside 14 and inulinotrioside 20 in high yields, 65 and 67%, respectively. These were transformed into new acceptors and also fully deprotected to afford the methyl glycosides of levanotriose and inulinotriose, all structures that have earlier not been accessible by chemical synthesis.

Carbohydrate Sequence↗

Interaction forces in thin liquid films stabilized by hydrophobically modified inulin polymeric surfactant. 1. Foam films.

Using the interferometric method of Scheludko-Exerowa for investigation of foam films, we have obtained results using a hydrophobically modified inulin polymeric surfactant (INUTEC SP1). Measurements were carried out at constant INUTEC SP1 concentration of 2 x 10(-)(5) mol.dm(-)(3) and at various NaCl concentrations (in the range 1 x 10(-)(4) to 2 mol.dm(-)(3)). At constant capillary pressure of 50 Pa, the film thickness decreased gradually with an increase in NaCl concentration up to 10(-)(2) mol.dm(-)(3) NaCl above which the film thickness remains virtually constant at about 16 nm. This reduction in film thickness with an increase in NaCl concentration is due to the compression of the double layer and at the critical electrolyte concentration (C(el,cr) = 10(-)(2) mol.dm(-)(3)) the electrostatic component of the disjoining pressure is completely screened and the remaining pressure is due to the steric interaction between the adsorbed polymer layers. Disjoining pressure-thickness (Pi-h) isotherms were obtained at C(el) < C(el,cr) (10(-)(4) - 10(-)(3) mol.dm(-)(3)) and C(el) > C(el,cr) (0.5, 1, and 2 mol.dm(-)(3)). In the first case, the disjoining pressure isotherms could be fitted using the classical DLVO theory, Pi = Pi(el) + Pi(vw), and using the constant charge model. At C(el) > C(el,cr), the main repulsion is due to the steric interaction between the polyfructose loops that exist at the air-water interface, i.e., Pi = Pi(st) + Pi(vw). Under these conditions, there is a sharp transition from DLVO to non-DLVO forces. In the latter case, the interaction could be described using the de Gennes' scaling theory. This gave an adsorbed layer thickness of 6.5 nm which is in reasonable agreement with the values obtained at the solid-solution interface. The Pi-h isotherms showed that these foam films are not very stable and they tend to collapse above a critical capillary pressure (of about 1 x 10(3) Pa), and these results could be used to predict the foam stability.

Electrolytes↗

Hyperglycemia with and without glycosuria: effect on inulin and para-amino hippurate clearance.

The response of the clearance of inulin (Cin) and para-amino hippurate (CPAH) to acute hyperglycemia with and without glycosuria was investigated in ten, healthy non-diabetic subjects. Standard methodology (UV/P) was used, with a mean clearance calculated from three, 15-minute urine collection periods. Each subject was studied at three levels of blood glucose (mmol/liter) concentration, mean (SE): Level 1, fasting, 4.5 (0.1); Level 2, hyperglycemia below renal threshold for glucose, 7.2 (0.1); Level 3, hyperglycemia with glycosuria, 12.6 (0.5). There was a significant rise in mean Cin (ml/min/1.73 m2) when changing from Level 1 (112[3]) to Level 2 (121[5]), with no further increase on changing to Level 3 (122[4]). With glycosuria Cin fell in some subjects. Mean CPAH (ml/min/1.73 m2) increased through Level 1 (560[27]) to Level 3 (603[34]), with consequently no change in mean filtration fraction at the three levels of glycemia. Our observations show a rise in glomerular filtration rate with mild hyperglycemia below renal threshold, with no further increase during hyperglycemia sufficient to produce glycosuria.

Adult↗

Measurement of glomerular filtration rate in ICU patients using 99mTc-DTPA and inulin.

Improved and reliable methods for assessing glomerular filtration rate (GFR) in intensive care patients are needed in light of known deficiencies using creatinine clearance. We compared simultaneous two-hour clearances of inulin (CIn), creatinine (CCr), and 99mTc-diethylenetriaminepentaacetic acid (CDTPA) in 18 medical or surgical intensive care patients (range, 49 to 92 years old) with blood urea nitrogen (BUN) levels greater than 17.9 mmol/liter (0.5 mg/ml), serum creatinine levels greater than 150 mumol/liter (0.02 mg/ml), or estimated Cockcroft clearance less than 60 ml/min. Patients had severe renal dysfunction with average GFR of 35 ml/min (range, 2 to 69 ml/min). CDTPA and CCr correlated significantly with CIn, although CDTPA tended to provide a closer approximation. Cockcroft clearance (32 +/- 4 ml/min) was grossly similar to CDTPA and CIn and correlated significantly, especially when weight was calculated using actual as opposed to ideal body weight. In a subset of 13 patients with CIn less than 30 ml/min, only CDTPA was significantly correlated with CIn. In patients in the intensive care unit, CDTPA provides a rapid, accurate, and inexpensive clinical assessment of GFR, even at very low GFRs.

Aged↗

Inulin-type fructans modulate gastrointestinal peptides involved in appetite regulation (glucagon-like peptide-1 and ghrelin) in rats.

The hypothesis tested in the present study is that dietary fructans are able to modulate gastrointestinal peptides involved in the control of food intake, namely glucagon-like peptide (GLP)-1 (7-36) amide and ghrelin. After 3 weeks of treatment with a standard diet (control) or the same diet enriched with 100 g fructans varying in their degrees of polymerization (oligofructose (OFS), Synergy 1 (Syn) or long chain inulin)/kg, male Wistar rats were deprived of food for 8 h before sample collection. Dietary energy intake throughout the experiment was significantly lower (P<0.05) in fructans-fed rats than in control rats, leading to a significant decrease (P<0.01) in epidydimal fat mass at the end of the treatment in OFS- and Syn-treated rats. GLP-1 (7-36) amide concentration in portal vein serum was higher in OFS- and Syn-fed than in control rats. Both GLP-1 (7-36) amide concentration and proglucagon mRNA concentrations were significantly greater (P<0.05) in the proximal colonic mucosa of fructans-fed rats v. controls. Normally active ghrelin concentration in plasma increases during food deprivation and rapidly falls during a meal. In the present study, after 8 h of food deprivation, active ghrelin in the plasma remained significantly lower (P<0.05) in OFS and Syn-fed than in control rats. These results are in accordance with the modifications of dietary intake and fat-mass development in short-chain fructans-treated rats and demonstrate the potential modulation of GLP-1 (7-36) amide and ghrelin by fermentable fibres such as fructans, which are rapidly and extensively fermented in the proximal part of the colon.

Animals↗

Intestinal immunity of rats with colon cancer is modulated by oligofructose-enriched inulin combined with Lactobacillus rhamnosus and Bifidobacterium lactis.

Probiotics (PRO) are known to modulate immunity in animals and human subjects and to inhibit colon carcinogenesis in experimental models, but the effects of synbiotics (SYN) are not well understood. Therefore, the effects of PRO (Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12), PRE (inulin-based enriched with oligofructose, 100 g/kg) and SYN (combination of PRO and PRE) on the immune system of rats were investigated in the azoxymethane (AOM)-induced colon cancer model. After 33 weeks, rats with and without AOM treatment were killed and immune cells were isolated from spleen, mesenterial lymph nodes (MLN) and Peyer's patches (PP). AOM treatment significantly reduced natural killer (NK) cell-like cytotoxicity in control rats and in PRO- and PRE-supplemented rats. SYN supplementation prevented the AOM-induced suppression of NK cell-like cytotoxicity in PP compared with control rats (P<0.01). SYN and PRE supplementation stimulated IL-10 production in PP in these rats (P<0.01) and in MLN of rats not treated with AOM (P<0.05). Interferon-gamma production in PP was decreased by PRO supplementation (PRO and SYN groups combined; P<0.05). Proliferative responsiveness of lymphocytes (PP) from AOM-treated rats was suppressed in SYN-supplemented rats (P<0.01). Overall, SYN supplementation in carcinogen-treated rats primarily modulated immune functions in the PP, coinciding with a reduced number of colon tumours. PRE and PRO provided in combination as SYN may contribute to the suppression of colon carcinogenesis by modulating the gut-associated lymphoid tissue.

Animals↗

Functional foods: concepts and application to inulin and oligofructose.

A food can be regarded as functional if it is satisfactorily demonstrated to affect beneficially one or more target functions in the body, beyond adequate nutritional effects, in a way which is relevant to either the state of well-being and health or the reduction of the risk of a disease. Health claims are expected to be authorized for functional foods based either on enhanced function (type A claim) or disease risk reduction (type B claim). Their development is a unique opportunity to contribute to the improvement of the quality of the food offered to consumer's choice for the benefit of his well-being and health. But only a rigorous scientific approach producing sound data will guarantee its success. The functional food components that are discussed in the proceedings of the 3rd ORAFTI Research Conference are the inulin-type fructans, natural food components found in miscellaneous edible plants. They are non-digestible oligosaccharides that are classified as dietary fiber. The targets for their functional effects are the colonic microflora that use them as selective 'fertilizers'; the gastrointestinal physiology; the immune functions; the bioavailability of minerals; and the metabolism of lipids. Potential health benefits may also concern reduction of the risk of some diseases like intestinal infections, constipation, non-insulin dependent diabetes, obesity, osteoporosis or colon cancer. The present proceedings review the scientific data available and, by reference to the concepts in functional food science, they assess the scientific evidence which will be used to substantiate health claims.

Bacteria↗

Inulin, oligofructose and mineral metabolism - experimental data and mechanism.

Numerous investigations performed in animal models in the past 10 years have shown repeatedly that non-digestible oligosaccharides (NDO), such as inulin, oligofructose or transgalacto-oligosaccharides (TOS), stimulate mineral absorption, mainly calcium and magnesium. Long-term beneficial effects on bone health have been indicated by accumulation of bone mineral content in growing rats or prevention of bone loss in ovariectomized rats. However, bone mineral content or density are not necessarily associated with bone quality. In recent studies both oligofructose and calcium prevented loss of trabecular bone area induced by oestrogen deficiency, this, however, occurred at different trabecular shapes. The effects of NDO on mineral metabolism may be based on the enhancement of passive and active mineral transport across the intestinal epithelium, mediated by an increase in certain metabolites of the intestinal flora and a reduction of pH. The possible impact of short-chain fatty acids, butyrate in particular, and of polyamines on the stimulation of mineral absorption capacity, and the interaction of oligofructose and antibiotics is discussed.

Animals↗

Extracellular fluid volume determined by a single injection of inulin in men with untreated essential hypertension.

The extracellular volume (ECV) and plasma volume (PV) were determined simultaneously in nine men with untreated essential hypertension and in nine healthy matched control subjects, using a single injection of inulin and of 131I-labelled human serum albumin, respectively. The average mean arterial blood pressure in the hypertensive group was 178/118 mmHg. ECV was nearly the same in the two groups, viz. 151 ml/kg body weight (SD 17) in the hypertensive group compared to 147 ml/kg (SD 16) in the control group. The corresponding figures for PV were 38.2 ml/kg body weight (SD 4.7) and 43.7 ml/kg (SD 7.9) respectively (P less than 0.1). The calculated interstitial fluid volume (IV) was 113 ml/kg (SD 16) and 103 ml/kg (SD 10) (P less than 0.2). The PV/IV ratio was significantly lower (P less than 0.02) in the hypertensive group (0.34, SD 0.06) than in the normal group (0.42, SD 0.06). The difference might suggest increased transcapillary water filtration in hypertension.

Adult↗

Idiotypes of inulin-binding myeloma proteins localized to variable region light and heavy chains: genetic significance.

Idiotypes of inulin-binding myeloma proteins (InuBMP) were determined primarly by variable region light chains (VL) or by variable region heavy chains (VH) but needed both chains to be expressed. Recombinant molecules were used to show that individual idiotypes (IdI) of U61, E109, T957, and A4 InuBMP and cross-specific idiotypes (IdXB) of U61 were primarily determined by VL while cross-specific idiotype (IdXA) of A4 was determined mainly by VH. The assignment of genes controlling idiotypes to VH based on allotype linkage (e.g., IdXB) is dubious until the role of the L chain in determining that idiotype is assessed. IdXB has been shown to be a VL-VH marker which presumably is controlled by two unlinked genes. However IdXB can be used as a L chain marker in combinations of strains differing in their L chain genes but having the same permissive H chain genes. Conversely IdXB can be used as a H chain marker in strains having the same permissive L chain genes but differing in their H chain genes.

Animals↗

Regulation of the anti-inulin antibody response by a nonallotype-linked gene.

The antibody response to the inulin [(In), beta-(2 leads to 1) fructosan] determinant of bacterial levan [(BL), a beta-(2 leads to 6) polyfructosan that contains beta-(2 leads to 1) branch points] requires the presence of the a haplotype of the Igh gene complex. BALB/c (Igh a) mice immunized with BL produce IgG anti-In antibodies of a single spectrotype by isoelectric focusing analysis. C57BL/6 mice, which possess the b haplotype of the Igh gene complex and which fail to produce anti-In antibodies, nevertheless possess a gene, spectrotype regulation gene 1 (Sr-1), that regulates the isoelectric focusing (IEF) pattern of anti-In antibodies in mice of the a haplotype. Thus, the IEF patterns of anti-In antibodies of (BALB/c x C57BL/6)F1 mice and of B.C8 mice (C57BL/Ka . Igh-Ca) are considerably more complex than those of BALB/c. Backcross analysis indicates that Sr-1 is not linked to the Igh complex, the major histocompatibility complex, or to the genes that code for coat color. Studies of the heterogeneity of anti-In antibodies in recombinant inbred lines and their progeny from matings to BALB/c and C.B20 (BALB/c . Igh-Cb) suggest the existence of other regulatory genes.

Animals↗

Antitumorigenic activity of the prebiotic inulin enriched with oligofructose in combination with the probiotics Lactobacillus rhamnosus and Bifidobacterium lactis on azoxymethane-induced colon carcinogenesis in rats.

Prebiotics such as fructans, and probiotics such as Lactobacilli or Bifidobacteria, or a combination of prebiotics and probiotics (synbiotics) are thought to be protective against colon cancer. Therefore, we studied whether the prebiotic inulin enriched with oligofructose (Raftilose-Synergy1, briefly, Synergy1, 10% of the diet), probiotics [Bifidobacterium lactis (Bb12) and Lactobacillus rhamnosus (LGG), each at 5x10(8) c.f.u./g diet] or synbiotics (a combination of the two) protect rats against azoxymethane (AOM)-induced colon cancer. Male F344 rats were divided into: Controls; PRE, which were fed a diet containing Synergy1; PRO, fed a diet containing LGG and Bb12; PREPRO, fed a diet containing Synergy1, LGG and BB12. Ten days after beginning the diets, rats were treated with AOM (15 mg/kg s.c. two times); dietary treatments were continued for the entire experiment. Thirty-one weeks after AOM, rats treated with Synergy1 (PRE and PREPRO groups) had a significantly lower (P < 0.001) number of tumours (adenomas and cancers) than rats without Synergy1 (colorectal tumours/rat were 1.9 +/- 1.7, 1.1 +/- 1.1, 2.2 +/- 1.4 and 0.9 +/- 1.2 in Controls, PRE, PRO and PREPRO groups, respectively, means +/- SD). A slight, not significant effect of probiotics in reducing malignant tumours was also observed (P = 0.079). Caecal short-chain fatty acids (SCFA) were higher (P < 0.001) in the groups treated with Synergy1. Apoptosis was increased in the normal mucosa of the PRO group, while no variation was observed in the tumours. Colonic proliferation was lower in the PRE group as compared with Controls. Glutathione S-transferase placental enzyme pi type expression, and to a lesser extent, inducible NO synthase were depressed in the tumours from rats in the PRE and PREPRO groups. Cycloxygenase-2 expression was increased in the tumours of control rats but not in those from PRE, PRO or PREPRO rats. In conclusion, prebiotic administration in the diet decreases AOM-induced carcinogenesis in rats.

Adenocarcinoma↗

Dietary modulation of the human gut microflora using the prebiotics oligofructose and inulin.

Although largely unproven in humans, better resistance to pathogens, reduction in blood lipids, antitumor properties, hormonal regulation and immune stimulation may all be possible through gut microflora manipulation. One approach advocates the oral intake of live microorganisms (probiotics). Although the probiotic approach has been extensively used and advocated, survivability/viability after ingestion is difficult to guarantee and almost impossible to prove. The prebiotic concept dictates that non viable dietary components fortify certain components of the intestinal flora (e.g., bifidobacteria, lactobacilli). This concept has the advantage that survival of the ingested ingredient through the upper gastrointestinal tract is not a prerequisite because it is indigenous bacterial genera that are targeted. The feeding of oligofructose and inulin to human volunteers alters the gut flora composition in favor of bifidobacteria, a purportedly beneficial genus. Future human studies that exploit the use of modern molecular-based detection methods for bacteria will determine the efficacy of prebiotics. It may be possible to address prophylactically certain gastrointestinal complaints through the selective targeting of gut bacteria.

Animals↗

Dose-response effects of inulin and oligofructose on intestinal bifidogenesis effects.

Recent studies have identified several beneficial attributes of inulin (I) and oligofructose (OF) in human health. However, most of the studies pertaining to the physiologic role of these compounds have been conducted at higher concentrations (8-40 g/d) as a source of dietary fiber. There is growing interest in using I and OF as a substrate for the selective growth of beneficial gastrointestinal bacteria such as the bifidobacteria. In vitro fermentation studies using fecal inoculums have shown that I and OF are utilized rapidly and completely by intestinal microflora and that the degree of polymerization of the substrate influenced its rate of disappearance. In these and other studies, I and OF were shown to be efficient substrates for the growth of most strains of bifidobacteria compared with glucose. In vivo studies have also shown that when human volunteers ingested I or OF, the number of fecal bifidobacteria increased. However, when results from the reported studies are combined and analyzed, a dose-response relationship in terms of log increases in the count of bifidobacteria cannot be demonstrated. Initial numbers of bifidobacteria in the feces, independent of the dose of the fructo-oligosaccharides, seem to influence the results. Future investigations should consider this relationship carefully.

Bifidobacterium↗

Petfood applications of inulin and oligofructose.

Published data on intestinal microbiota of dogs and cats are limited but suggest the presence of a complex and diverse colonic bacterial population (34 genera including 129 species) the majority of which are anaerobes. During the colonic fermentation of endogenous and undigested amino acids, several putrefactive compounds (i.e., ammonia, aliphatic amines, indoles, phenols and volatile sulfur-containing compounds) are produced and are responsible for the malodor of dog and cat feces. These fecal odor components also have been implicated as causes of colorectal cancer; therefore, dietary manipulation of gut microbiota towards a potentially more remedial community (Bifidobacterium and Lactobacillus) is gaining more attention. The health benefits derived from dietary supplementation of prebiotics (e.g., oligofructose and inulin) have been documented in humans. However, little is known of a potentially similar role in companion animals. Feeding another prebiotic (i.e., lactosucrose) to dogs or cats is reported to increase the numbers of bifidobacteria and decrease the numbers of pathogens and the concentration of fecal odor components. In our laboratory, oligofructose supplementation numerically decreased the concentrations of ammonia and amines and increased the numbers of bifidobacteria in dog feces.

Animal Feed↗

Influence of inulin and oligofructose on breast cancer and tumor growth.

Because anticarcinogenic and tumor-growth-inhibiting effects of nonsoluble fibers have been described, similar actions of soluble fibers appear to merit investigation. In a preliminary study on methylnitrosourea-induced mammary carcinogenesis in Sprague-Dawley female rats, 15% oligofructose added to the basal diet modulated this carcinogenesis in a negative manner. There was a lower number of tumor-bearing rats and a lower total number of mammary tumors in oligofructose-fed rats than in the group fed the basal diet alone. The effect of dietary nondigestible carbohydrates (15% oligofructose, inulin or pectin incorporated into the basal diet) on the growth of intramuscularly transplanted mouse tumors, belonging to two tumor lines (TLT and EMT6), was also investigated. The results were evaluated by regular tumor measurements with a vernier caliper. The mean tumor surface in the experimental groups was compared with that in animals of the control group fed the basal diet containing starch as the only carbohydrate. The growth of both tumor lines was significantly inhibited by supplementing the diet with nondigestible carbohydrates. Such nontoxic dietary treatment appears to be easy and risk free for patients, applicable as an adjuvant factor in the classical protocols of human cancer therapy.

Adenocarcinoma↗