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Intestinal anti-inflammatory activity of dietary fiber (Plantago ovata seeds) in HLA-B27 transgenic rats.

BACKGROUND & AIMS: Dietary fiber has been proven to be beneficial in maintaining remission in human ulcerative colitis, an effect related with an increased luminal production of short-chain fatty acids (SCFA). The aim of the present study was to further investigate the mechanisms involved in the intestinal anti-inflammatory effects of dietary fiber in an experimental model of rat colitis. METHODS: HLA-B27 transgenic rats (8-10 weeks old) were fed a fiber-supplemented diet (5% Plantago ovata seeds) for 13 weeks before evaluation of the colonic inflammatory status, both histologically and biochemically. The luminal colonic production of SCFA was quantified. In vitro studies were also performed to test the interaction between two SCFA (butyrate and propionate) as inhibitors of cytokine production in THP-1 cells. RESULTS: Dietary fiber supplementation ameliorated the development of colonic inflammation in transgenic rats as evidenced by an improvement of intestinal cytoarchitecture. This effect was associated with a decrease in some of the pro-inflammatory mediators involved in the inflammatory process: nitric oxide, leukotriene B(4), tumor necrosis factor alpha (TNFalpha). The intestinal contents from fiber-treated colitic rats showed a significant higher production of SCFA, butyrate and propionate, than non-treated colitic animals. In vitro studies revealed a synergistic inhibitory effect of butyrate and propionate on TNFalpha production. CONCLUSIONS: Dietary fiber supplementation ameliorated colonic damage in HLA-B27 transgenic rats. This effects was associated with an increased production of SCFA, which can act synergistically in inhibiting the production of pro-inflammatory mediators.

Animals↗

Effect of ispaghula husk on the faecal output of bile acids in healthy volunteers.

Faecal bile acids are associated with both colorectal cancer and serum cholesterol levels. We investigate whether dosing with ispaghula husk affects the faecal bile acid weights and concentrations in healthy adults. Sixteen healthy volunteers consumed 7.0 g/day ispaghula husk, containing 5.88 g/day Englyst-determinable dietary fibre, for the middle 8 weeks of a 12-week period. Stool samples were collected, analysed for faecal bile acids and their form and dry weight determined. Correlations between the faecal bile acids, the stool parameters and the dietary intake were tested. Ispaghula husk treatment significantly lowers faecal lithocholic and isolithocholic acids and the weighted ratio of lithocholic acids to deoxycholic acid. These effects revert towards their initial states at the end of the treatment period. These changes in the faecal bile acid profiles indicate a reduction in the hydrophobicity of the bile acids in the enterohepatic circulation.

Adult↗

Occupational asthma related to aescin inhalation.

BACKGROUND: More than 400 agents are recognized as causes of occupational asthma, a work-related disease that can be induced by an immunologic or a nonimmunologic mechanism. OBJECTIVE: To describe a 57-year-old man employed in the pharmaceutical industry who developed bronchial asthma while working with products such as Plantago ovata and aescin, an active ingredient with anti-inflammatory and venotonic properties. METHODS: Various tests were performed, including radiography, total serum IgE titer measurements, skin tests against common pneumoallergens and Plantago species, pulmonary function studies, a methacholine test, and specific inhalation challenge with P. ovata and aescin. RESULTS: The results of these tests, including specific inhalation challenge, confirmed the diagnosis of occupational asthma due to aescin exposure, whereas the results of specific challenge with P. ovata, a known cause of occupational asthma, were negative. CONCLUSIONS: Aescin may represent a new causative agent of occupational asthma in personnel working in the pharmaceutical industry. The mechanism by which aescin can produce asthma is unknown, but analysis of the characteristics of our patient suggests a non-IgE immunologic mechanism, although an irritative mechanism secondary to long-term low-level exposure to aescin, a possible irritant, cannot be ruled out.

Asthma↗

Effects of guar gum, ispaghula and microcrystalline cellulose on abdominal symptoms, gastric emptying, orocaecal transit time and gas production in healthy volunteers.

BACKGROUND: Dietary fibres are carbohydrates that resist hydrolysis by human intestinal enzymes but are fermented by colonic microflora. Soluble dietary fibres are fermented by anaerobic bacteria with production of gases, short chain fatty acids and other metabolic products believed to cause symptoms such as bloating, abdominal distension, flatulence. Insoluble fibres are only partially fermented, serving almost exclusively as bulking agents that result in shorter transit time and increased faecal mass. AIMS: To evaluate effect of a supplementation of a single 5 g dose of dietary fibre to a solid meal on gastric emptying, orocaecal transit time, gas production and symptom genesis, in healthy volunteers. Three different dietary fibres were tested, two soluble (guar gum and ispaghula] and one insoluble (microcrystalline cellulose). PATIENTS AND METHODS: After a 24-hour low fibre diet, 10 healthy subjects had a standard meal consisting of white bread and one 70 g egg the yolk of which was mixed with 100 mg of 13C octanoic acid and fried. Breath samples were collected for 13CO2 measurements with a mass spectrophotometer and excretion curve (Tlag, T1/2) evaluation. Further breath samples were collected and analysed with a gas chromatograph for the evaluation of H2 and CH4 production and orocaecal transit time. Each evaluation was repeated adding to standard meal, diluted in 300 ml tap water, respectively: a single 5 g dose of microcrystalline cellulose, guar gum or ispaghula. Subjects were asked to report all symptoms experienced from time of meal ingestion over 24 hours, evaluating the intensity. RESULTS: Dietary fibres did not significantly change gastric emptying (Tlag, T1/2) and orocaecal transit time of standard meal. Subjects experienced more symptoms when meals were supplemented with guar gum (p=0.009 vs standard meal) and ispaghula (p=0.048 vs standard meal). There was a poor, but significant, correlation between gas production and symptoms (r=0. 38, p=0. 01). CONCLUSIONS: Addition of different dietary fibres to a solid meal did not influence gastric emptying and orocaecal transit time. Microcrystalline cellulose caused fewer symptoms than guar gum and ispaghula probably due to the insoluble nature and the dimensions of the particles of this micronised cellulose.

Adult↗

Effects of ispaghula husk and guar gum on postprandial glucose and insulin concentrations in healthy subjects.

OBJECTIVE: The aim of this study was to evaluate, under the same experimental conditions and in the same subjects, the effects of ispaghula husk and guar gum on postprandial glucose and insulin concentrations in healthy female subjects. DESIGN: An oral glucose load with and without fiber was administered in the morning after an overnight fast. The study of the fiber effect was planned according to a randomized and cross-over design. SETTING: The study was performed at the Department of Pharmacology, Toxicology and Nursing at the University of León (Spain). SUBJECTS: Ten healthy female volunteers aged 30-48 y with normal body mass indices participated in this study. RESULTS: A significant decrease in mean serum insulin concentrations was observed from 30 to 90 min in the presence of both fibers. The area under the insulin curve was significantly reduced by 36.1% for ispaghula husk and 39.4% for guar gum. The area under the glucose curve was reduced by 11.1% (significant difference) for ispaghula husk and 2.6% for guar gum (no significant difference). CONCLUSIONS: According to the results obtained in this study, the administration of ispaghula husk may be beneficial due to its ability to reduce glucose postprandial concentration and especially insulin requirements. Individualization of the treatment would be advisable due to large individual variations observed in glycemic and insulinemic postprandial responses.

Adult↗

The effect of ispaghula (Fybogel and Metamucil) and guar gum on glucose tolerance in man.

The effects of incorporating Fybogel (3.5 and 7 g doses), Metamucil (7 g) or guar gum (2.5 and 14.5 g doses) in a drink containing 50 g glucose on plasma glucose, plasma insulin and gastric emptying were studied in thirty-eight normal volunteers. In addition, the effects of Fybogel (7 g) on glucose tolerance, plasma insulin and gastric emptying were measured in fourteen non-insulin-dependent diabetics. Both doses of guar gum significantly lowered plasma glucose and plasma insulin responses to the oral glucose load in normal subjects, although 14.5 g guar gum did not delay the half-time for gastric emptying. Neither Fybogel nor Metamucil had significant effects on plasma glucose responses in normal subjects. In addition, Fybogel (at either dose) had no significant effects on plasma insulin levels, or on gastric emptying in normal subjects or on plasma glucose and insulin responses in diabetic patients. The viscosity of ispaghula solutions ( Fybogel ) was lower than that of guar gum solutions.

Adult↗

The relation between bacterial degradation of viscous polysaccharides and stool output in human beings.

1. The relation between bacterial degradation of three viscous polysaccharides (guar gum, ispaghula and xanthan gum) by colonic bacteria in vitro and their effects on colonic function were investigated by comparing the results of anaerobic in vitro incubations with fresh faeces from seven healthy volunteers (measuring viscosity, pH and gas production) with the effects of feeding all three polysaccharides to the same volunteers for 1 week each (14-15 g/d) on faecal mass and whole-gut transit time. 2. Guar gum was rapidly fermented in vitro by faecal bacteria from all volunteers with concomitant loss of viscosity, reduction in pH and generation of gases. Ispaghula maintained its viscosity during incubation, but the pH fell significantly. The results of xanthan gum incubations showed considerable individual variation. 3. Only ispaghula significantly increased faecal mass, whilst none of the gums significantly affected stool frequency or transit time. Statistical analysis of the pooled results showed that although transit time and faecal output were inversely related, feeding viscous polysaccharides could influence these indices independently. Stool frequency was significantly correlated with the transit time, but not the faecal output. 4. Transit time was reduced by gum feeding to a significantly greater extent in those subjects whose faecal bacteria reduced or removed the viscosity of that gum, than in those subjects where the viscosity was maintained. In contrast, there was a smaller increase in faecal mass when the viscosity of the appropriate cultures was removed than when it was maintained or reduced. Increases in stool frequency were significantly associated with hydrogen production from in vitro cultures.

Adult↗

Plantago ovata seeds as dietary fibre supplement: physiological and metabolic effects in rats.

In rats, the effects of a 4-week supplementation of a fibre-free elemental diet with 100 or 200 g Plantago ovata seeds/kg was compared with that of the husks and wheat bran. The seeds increased faecal fresh weight up to 100%, faecal dry weight up to 50% and faecal water content up to 50%. The husks, at the high concentration only, were more effective and wheat bran less effective. Length and weight of the small intestine were not greatly affected by the seeds, but both variables increased significantly in the large intestine. The husks had more pronounced effects, especially in the small intestine, and wheat bran almost no effect. Faecal bacterial mass as estimated from the 2,6-diaminopimelic acid output was increased to the greatest extent by the seed-containing diet and by the high concentration of husks, but to a lesser extent by wheat bran. Faecal and caecal protein content was enhanced by the seeds and wheat bran, but to a lesser extent by the husks. Total acetate in caecal contents or faeces was highest on the seeds and husks diet and not elevated by wheat bran. Total faecal bile acid excretion was stimulated and beta-glucuronidase (EC 3.2.1.31) activity reduced by both Plantago ovata preparations, but not by wheat bran. Mucosal digestive enzyme activities were inhibited to different degrees by all dietary fibres in the jejunum, and sometimes activated in the ileum. These results suggest that Plantago ovata seeds are a partly-fermentable dietary fibre supplement which increases stool bulk; metabolic and mucosa-protective effects are also probable.

Animals↗

The effects of ispaghula on rat caecal fermentation and stool output.

The colonic fermentation of ispaghula, a mucilage from Plantago ovata composed mainly of arabinoxylans, and its effects on stool output and caecal metabolism were investigated. Four groups of eight rats were fed on a basal diet (45 g non-starch polysaccharides/kg) for 28 d. The diet was then supplemented with ispaghula (g/kg; 0, 5, 15 or 50) for 28 d. Ispaghula increased stool dry weight and apparent wet weight but faecal water-holding capacity (amount of water held per g dry faecal material at 0.2 mPa) was unchanged. The extent of faecal drying in the metabolism cages was measured for rats fed on the basal diet and 50 g ispaghula/kg diet. At the faecal output levels encountered, only an 8% loss of wet weight would be predicted over 24 h and this was independent of diet. Faecal short-chain fatty acid (SCFA) concentration did not change but SCFA output increased. The molar proportion of SCFA as propionic acid increased and faecal pH was reduced. Values from pooled faecal samples suggested that approximately 50% of the ingested ispaghula was excreted by the 50 g ispaghula/kg diet group. Diaminopimelic acid (a constituent of bacterial cells) concentrations fell but output was unchanged indicating no change in bacterial mass. Similar changes were seen in the caecal contents but caecal pH and SCFA were unaffected. Ispaghula increased both caecal and colonic tissue wet weight and colonic length. Our results suggest that ispaghula is partly fermented in the rat caecum and colon, and loses its water-holding capacity. However, it is still an effective stool bulker and acts mainly by increasing faecal water by some unknown mechanism.

Animals↗

Involvement of small intestinal motility in blood glucose response to dietary fibre in man.

Three dietary fibres with different physicochemical properties were studied in healthy humans for their effects on small intestinal motility and postprandial hyperglycaemia. Duodeno-jejunal motor activity was evaluated electromyographically for 180 min in six subjects who had ingested a test meal composed of glucose alone or glucose with 15 g of wheat bran (WB), sugar beet (SB) or ispaghula (I) fibres. Glucose and insulin concentrations were determined during the same period. Each subject received each of the four test meals randomly during a 4 d period. Addition of SB or I to the glucose meal altered duodeno-jejunal motility. Both of these fibres inhibited stationary contractile activity and increased the propagation length and velocity of propagated activity, whereas addition of WB had no effect. These results could reflect the high water-holding capacity of SB and I. Blood glycaemic response to the glucose meal was reduced by SB and I but remained unchanged with WB. Postprandial blood glucose levels were significantly correlated with the total motility index (r 0.82) and stationary activity (r 0.79). Taken together, these observations suggest that the contractile activity induced by dietary fibre in the small intestine probably plays a major role in delayed glucose absorption.

Adult↗

Caecal and faecal short-chain fatty acids and stool output in rats fed on diets containing non-starch polysaccharides.

The exact mechanisms by which non-starch polysaccharides increase stool output are unknown. In the present study the hypothesis that the site of fermentation and short-chain fatty acid (SCFA) accumulation is related to the action of non-starch polysaccharides (NSP) on stool output was tested. The basal diet (45 g NSP/kg) of forty-three male Wistar rats was supplemented with 50 g/kg of either guar, karaya, tragacanth, gellan, xanthan or ispaghula for 28 d. A further twenty-three rats were maintained on the basal diet for the same time period. Faeces were then collected over 2 d and caecal contents obtained post-mortem. Caecal and faecal wet and dry weights and SCFA were measured. Each supplement had a different effect on the caecal and faecal contents but they appeared to fall into three groups when compared with the basal diet. In group 1, guar gum affected only caecal SCFA. It had no effect on stool output or faecal SCFA. In group 2, karaya increased caecal SCFA and tragacanth, karaya and xanthan increased faecal SCFA and faecal water. In group 3, ispaghula and gellan had no consistent effect on caecal or faecal SCFA concentrations but increased total faecal SCFA output and increased faecal wet and dry weight. Although the knowledge that SCFA are rapidly absorbed in the large intestine has led us to believe that they play no role in determining faecal output, these results suggest that in some cases where NSP are slowly fermented, and increase faecal SCFA, the role of the SCFA may need to be reassessed.

Animals↗

Molecular weight, tertiary structure, water binding and colon behaviour of ispaghula husk fibre.

Molecular variables, using aqueous and alkaline extracts, of the polysaccharide from ispaghula husk (IH) were examined using gel-permeation chromatography linked to multi-angle laser light scattering. Progressive extraction can yield a component with a molecular weight (MW)value up to about 7 x 106 Da, and gels, which accompany the extraction, have MW ranging from 10-20 x 106 Da. To mimic the polysaccharide degradation, particularly in the colon, the solid IH was degraded progressively using ionising radiation. A chain break occurs every 7.5 kGy in NaOH and every 15 kGy in water. The solid-state matrix is opened by the radiation to yield increased visco-elasticity of the aqueous extracts at critical radiation doses, before further degradation occurs after about 12 kGy. Differential scanning calorimetry is used to study the mechanism of interaction of water with IH. The first water to be taken up is non-freezing water and represents about twelve water molecules/disaccharide unit of the polysaccharide. As the water content is increased, the water becomes bound to the polysaccharide and freezes and melts at a temperature different from free water. This water is thermodynamically distinguishable from free water. It forms amorphous ice on cooling which crystallises exothermically and subsequently melts endothermically. Saturation occurs at a water content of 2-3 g water/g polymer, showing that about 60% of the water in the system is 'bound'. The most surprising conclusion is that despite the fact that the IH swells in water to form a solid and stiff gel, the greater part of that water in the gel is still free and behaves like liquid water.

Chromatography, Gel↗

Primary structure of arabinoxylans of ispaghula husk and wheat bran.

The primary structures of ispaghula husk and wheat bran were investigated in order to determine how and why these fibres are among the most beneficial dietary fibres. To this end, the polysaccharide preparations have been subjected to enzymic hydrolysis and methylation analysis.The results have shown ispaghula husk and wheat bran to be very-highly-branched arabinoxylans consisting of linear f-D-(1-4)-linked xylopyranose (Xylp) backbones to which a-L-arabinofuranose (AraJ3 units are attached as side residues via a-(l13) and a-(1-02) linkages.Other substituents identified as present in wheat bran include P-D-glucuronic acid attached via the C(O)-2 position, and arabinose oligomers, consisting of two or more arabinofuranosyl residues linked via 1-2, 1-3, and 1-4 linkages. Ispaghula-husk arabinoxylan is more complex having additional side residues which include a-D-glucuronopyranose (GalAp)-(1-42)-linked-a-L-rhamnopyranose-(1-04)-0-D-Xylp, a-D-GalAp-(l-o3)-linked-a-L-Araf-(l-4)-[3-D-Xylp, and a-L-Araf-(l-43)-linked-P-D-Xylp-(1l -4)--D-Xylp. The beneficial effects of increased faecal bulk and water-holding capacity are undoubtedly related to the structures of the arabinoxylans, with differences in their efficacy to treat various functional bowel disorders due to their specific structural features.

Carbohydrate Sequence↗