Dietary glycated protein modulates the colonic microbiota towards a more detrimental composition in ulcerative colitis patients and non-ulcerative colitis subjects

Aim: To investigate the effect of native, heated and glycated bovine serum albumin (BSA) on the ulcerative colitis (UC) and non-UC colonic microbiota in vitro. Methods and Results: Continuous flow culture (CFC) models of the human colonic microbiota inoculated with faeces from UC and non-UC volunteers were maintained on BSA as growth substrate. Changes in bacterial populations and short-chain fatty acids were determined. UC and non-UC microbiota differed significantly in microbial populations, with elevated numbers of sulfate-reducing bacteria (SRB) and clostridia in the microbiota from UC patients. Compared with native BSA, glycated BSA modulated the gut microbiota of UC patients in vitro towards a more detrimental community structure with significant increases in putatively harmful bacteria (clostridia, bacteroides and SRB; P < 0.009) and decreases in dominant and putatively beneficial bacterial groups (eubacteria and bifidobacteria; P < 0.0004). The levels of beneficial short-chain fatty acids were significantly decreased by heated or glycated BSA, but were increased significantly by native BSA. Conclusion: The UC colonic microbiota maintained in CFC was significantly modified by glycated BSA. Significance and Impact of the Study: Results suggest that dietary glycated protein may impact upon the composition and activity of the colonic microbiota, an important environmental variable in UC.

Evaluation of the inclusion of a mixture of organic acids or lactulose into the feed of pigs experimentally challenged with Salmonella Typhimurium

A mixture of organic acids and lactulose for preventing or reducing colonization of the gut by Salmonella Typhimurium was evaluated in pigs. A total of 63 4-week-old commercial piglets were randomly distributed into three different experimental dietary groups: a plain diet without additives (PD) and the same diet supplemented with either 0.4% (w/v) formic acid and 0.4% lactic acid (w/v) (AC) or 1% (w/v) lactulose (LC). After 7 days of adaptation, two-thirds of the pigs (14 from each diet) were challenged with a 2-mL oral dose of 10(8) CFU/mL of Salmonella Typhimurium, leaving the remaining animals unchallenged (UC). After 4 and 10 days post-challenge, pigs were euthanized and the ileum and caecum content were aseptically sampled to (a) quantify lactic, formic, and short-chain fatty acids (SCFA), (b) quantify bacterial populations and Salmonella by fluorescence in situ hybridization and (c) qualitatively analyse bacterial populations through denaturing gradient gel electrophoresis (DGGE). Modification of fermentation products and counts of some of the bacterial groups analysed in the challenged pigs receiving the treatments AC and LC were minimal. Treatments only influenced the bacterial diversity after 10 days post-challenge, with AC generating a lower number of DGGE bands than UC(P < 0.05). Neither the inclusion of a mixture of 0.4% (w/v) formic and 0.4% (w/v) lactic acids nor of 1% (w/v) lactulose in the feed influenced numbers of Salmonella in the ileum and caecum of experimentally challenged pigs. (C) 2009 Elsevier B.V. All rights reserved.

Dietary vitamin C down-regulates inflammatory gene expression in apoE4 smokers

The deleterious impact of cigarette smoking on cardiovascular health may be in part attributable to a free radical mediated proinflammatory response in circulating monocytes. In the current investigation, the impact of vitamin C supplementation on monocyte gene expression was determined in apoE4 smokers versus non-smokers. A total of 10 smokers and 11 non-smokers consumed 60 mg/day of vitamin C for four weeks and a fasting blood sample was taken at baseline and post-intervention for the determination of plasma vitamin C and monocyte gene expression profiles using cDNA array and real time PCR. In apoE4 smokers, supplementation resulted in a 43% increase in plasma vitamin C concentrations. Furthermore, a number of genes were differentially expressed more than 2-fold in response to treatment, including a downregulation of the proinflammatory mediators tumor necrosis factor (TNF) beta, TNF receptor, neurotrophin-3 growth factor receptor, and monocyte chemoattractant protein I receptor. The study has identified a number of molecular mechanisms underlying the benefit of vitamin C supplementation in smokers. (c) 2005 Elsevier Inc. All rights reserved.

Degradation products of clavulanic acid promote clavulanic acid production in cultures of Streptomyces clavuligerus

The role of clavulanic acid, an unstable antibiotic produced by Streptomyces clavuligerus, in biomass accumulation and production of clavulanic acid in batch cultures of the organism was examined. The organism was grown in a medium containing either 20 g/l lysine, 1 g/l lysine or 1 g/l lysine supplemented with degraded clavulanic acid as nitrogen sources. Biomass accumulation was highest in cultures grown with supplemented degraded clavulanic acid and reached a maximum of 2.2 g/l, compared with 1.5 g/l when lysine only was used. The yield coefficient for clavulanic acid production was again highest in cultures grown with supplemented degraded clavulanic acid, with a Y-p/x, value of 2 mg/g compared with Y-p/x value of 1.5 mg/g in 20 g/l lysine. No clavulanic acid was produced in cultures containing non-supplemented 1 g/l lysine. Non-degraded clavulanic, acid was added at 60 h to non-producing cultures of the organism containing 1 g/l lysine only. Clavulanic acid concentration immediately decreased on addition from 0.04 g/l over a period of 20 h, then remained constant at 0.02 g/l for a further 30 h until the end of the cultivation. This suggests that the rate of degradation was equivalent to the rate of production of clavulanic acid following a period of initial additive degradation. These results indicate that clavulanic acid is both produced and degraded in cultures of S. clavuligerus and that the products of degradation are used by the organism, resulting in further production of the antibiotic. (C) 2003 Elsevier Inc. All rights reserved.

Functional food, blood lipids and cardiovascular disease. Part 1: probiotics

For the past 20 years, the focuses of public health strategies for reducing the risk of cardiovascular disease (CVD) have been aimed at lowering cholesterol levels. However recent findings have highlighted not only cholesterol but also triacylglycerol as a lipid risk factor for CVD. Dietary strategies which are able to reduce these circulating lipid levels, but which are able to offer long-term efficacy comparable with effective drug treatments, are currently being sought. One dietary strategy that has been proposed to benefit the lipid profile involves the supplementation of the diet with probiotics (Part 1), prebiotics and synbiotics (Part 2), which are mechanisms to improve the health of the host by supplementation and/or fortification of certain health promoting gut bacteria. Probiotics in the form of fermented milk products have been shown to have cholesterol-lowering properties, whereas non-digestible fermentable prebiotics have been shown to reduce triacylglycerol levels in animal studies. However in humans studies, there have been inconsistent findings with respect to changes in lipid levels with both prebiotics and probiotics although on the whole there have been favourable outcomes.

Symposium on 'nutrition interventions in high-risk groups' - CVD risk in South Asians: the importance of defining adiposity and influence of dietary polyunsaturated fat

The prevalence of the metabolic syndrome (MetS), CVD and type 2 diabetes (T2D) is known to be higher in populations from the Indian subcontinent compared with the general UK population. While identification of this increased risk is crucial to allow for effective treatment, there is controversy over the applicability of diagnostic criteria, and particularly measures of adiposity in ethnic minorities. Diagnostic cut-offs for BMI and waist circumference have been largely derived from predominantly white Caucasian populations and, therefore, have been inappropriate and not transferable to Asian groups. Many Asian populations, particularly South Asians, have a higher total and central adiposity for a similar body weight compared with matched Caucasians and greater CVD risk associated with a lower BMI. Although the causes of CVD and T2D are multi-factorial, diet is thought to make a substantial contribution to the development of these diseases. Low dietary intakes and tissue levels of long-chain (LC) n-3 PUFA in South Asian populations have been linked to high-risk abnormalities in the MetS. Conversely, increasing the dietary intake of LC n-3 PUFA in South Asians has proved an effective strategy for correcting such abnormalities as dyslipidaemia in the MetS. Appropriate diagnostic criteria that include a modified definition of adiposity must be in place to facilitate the early detection and thus targeted treatment of increased risk in ethnic minorities.

Dietary, physiological, genetic and pathological influences on postprandial lipid metabolism

Most of diurnal time is spent in a postprandial state due to successive meal intakes during the day. As long as the meals contain enough fat, a transient increase in triacylglycerolaemia and a change in lipoprotein pattern occurs. The extent and kinetics of such postprandial changes are highly variable and are modulated by numerous factors. This review focuses on factors affecting postprandial lipoprotein metabolism and genes, their variability and their relationship with intermediate phenotypes and risk of CHD. Postprandial lipoprotein metabolism is modulated by background dietary pattern as well as meal composition (fat amount and type, carbohydrate, protein, fibre, alcohol) and several lifestyle conditions (physical activity, tobacco use), physiological factors (age, gender, menopausal status) and pathological conditions (obesity, insulin resistance, diabetes mellitus). The roles of many genes have been explored in order to establish the possible implications of their variability in lipid metabolism and CHD risk. The postprandial lipid response has been shown to be modified by polymorphisms within the genes for apo A-I, A-IV, AN, E, B, C-I and C-III, lipoprotein lipase, hepatic lipase, fatty acid binding and transport proteins, microsomal trigyceride transfer protein and scavenger receptor class B type I. Overall, the variability in postprandial response is important and complex, and the interactions between nutrients or dietary or meal compositions and gene variants need further investigation. The extent of present knowledge and needs for future studies are discussed in light of ongoing developments in nutrigenetics.

The reaction of flavanols with nitrous acid protects against N-nitrosamine formation and leads to the formation of nitroso derivatives which inhibit cancer cell growth

Studies have suggested that diets rich in polyphenols Such as flavonoids may lead to a reduced risk of gastrointestinal cancers. We demonstrate the ability of monomeric and dimeric flavanols to scavenge reactive nitrogen species derived from nitrous acid. Both epicatechin and dimer B2 (epicatechin dimer) inhibited nitrous acid-induced formation of 3-nitrotyrosine and the formation of the carcinogenic N-nitrosamine, N-nitrosodimethylamine. The reaction of monomeric and dimeric epicatechin with nitrous acid led to the formation of mono- and di-nitroso flavanols, whereas the reaction with hesperetin resulted primarily in the formation of nitrated products. Although, epicatechin was transferred across the jejunum of the small intestine yielding metabolites, its nitroso form was not absorbed. Dimer B2 but not epicatechin monomer inhibited the proliferation of, and triggered apoptosis in, Caco-2 cells. The latter was accompanied by caspase-3 activation and reductions in Akt phosphorylation, suggesting activation of apoptosis via inhibition of prosurvival signaling. Furthermore, the dinitroso derivative of dimer B2, and to a lesser extent the dinitroso-epicatechin, also induced significant toxic effects in Caco-2 cells. The inhibitory effects on cellular proliferation were paralleled by early inhibition of ERK 1/2 phosphorylation and later reductions in cyclin D I levels, indicating modulation of cell cycle regulation in Caco-2 cells. These effects highlight multiple routes in which dietary derived flavanols may exert beneficial effects in the gastrointestinal tract. (c) 2005 Elsevier Inc. All rights reserved.

Investigations on the effect of amino acids on acrylamide, pyrazines, and Michael addition products in model systems

Acrylamide and pyrazine formation, as influenced by the incorporation of different amino acids, was investigated in sealed low-moisture asparagine-glucose model systems. Added amino acids, with the exception of glycine and cysteine and at an equimolar concentration to asparagine, increased the rate of acrylamide formation. The strong correlation between the unsubstituted pyrazine and acrylamide suggests the promotion of the formation of Maillard reaction intermediates, and in particular glyoxal, as the determining mode of-action. At increased amino acid concentrations, diverse effects were observed. The initial rates of acrylamide formation remained high for valine, alanine, phenylalanine, tryptophan, glutamine, and Ieucine, while a significant mitigating effect, as evident from the acrylamide yields after 60 min of heating at 160 degrees C, was observed for proline, tryptophan, glycine, and cysteine. The secondary amine containing amino acids, proline and tryptophan, had the most profound mitigating effect on acrylamide after 60 min of heating. The relative importance of the competing effect of added amino acids for alpha-dicarbonyls and acrylamide-amino, acid alkylation reactions is discussed and accompanied by data on the relative formation rates of selected amino acid-AA adducts.

The acceptability of isoflavones as a treatment of menopausal symptoms: a European survey among postmenopausal women

Objective: To investigate determinants of the acceptability of isoflavone products among postmenopausal women with regard to social and lifestyle factors, dietary habits, health concerns, food beliefs, menopausal symptoms and therapies, and to elucidate preferences for specific products. Methods: A consumer survey was conducted among postmenopausal women in four European countries (Germany, Denmark, Italy and the UK), including a total of 465 respondents. Results: The declared acceptability of isoflavones was highest in Germany (80%), followed by Italy (75%), the UK (59%) and Denmark (55%; p < 0.001). Among other factors, prior information about isoflavones (odds ratio (OR) 2.64, 95% confidence interval (CI) 1.54-4.51, p < 0.001) and belief that foods can be used to treat medical conditions (OR 2.18, 95% CI 1.17-4.05, p=0.014) were the strongest predictors of potential acceptability. The preferred forms in which isoflavones might be taken differed markedly between countries. Conclusions: Information about the health effects of isoflavones and health-diet links should be considered the most important factors in attempts to influence the potential acceptability of isoflavone products. Foods enriched with isoflavones need to be developed with regard to specific cultural demands in order to assure consumer acceptance on the marketplace.

Gut fermentation products of insulin-derived prebiotics beneficially modulate markers of tumour progression in human colon tumour cells

Insulin is a prebiotic food ingredient, which suppresses colon tumour growth and development in rats. In the gut lumen, it is fermented to lactic acid and short chain fatty acids (SCFA). Of these, butyrate has suppressing agent activities, but little is known concerning cellular responses to complex fermentation samples. To investigate the effects of fermentation products of insulin on cellular responses related to colon carcinogenesis. Fermentations were performed in anaerobic batch cultures or in a three-stage fermentation model that simulates conditions in colon-segments (proximal, transverse, distal). Substrate was insulin enriched with oligofructose (Raftilose® Synergy1), fermented with probiotics (Bifidobacterium lactis Bb12, Lactobacillus rhamnosus GG), and/or faecal inocula. HT29 or CaCo-2 cells were incubated with supernatants of the fermented samples (2.5%-25% v/v, 24-72 hours). Cellular parameters of survival, differentiation, tumour progression, and invasive growth were determined. Fermentation supernatants derived from probiotics and Synergy1 were more effective than with glucose. The additional fermentation with faecal slurries produced supernatants with lower toxicity, higher SCFA contents, and distinct cellular functions. The supernatant derived from the gut model vessel representing the distal colon, was most effective for all parameters, probably on account of higher butyrate-concentrations. Biological effects of insulin upon colon cells may be mediated not only by growth stimulation of the lactic acid-producing bacteria and/or production of butyrate, but also by other bacteria and products of the gut lumen. These newly reported properties of the supernatants to inhibit growth and metastases in colon tumour cells are important mechanisms of tumour suppression.

Dietary supplementation with a natural carotenoid mixture decreases oxidative stress

Objective: To determine whether dietary supplementation with a natural carotenoid mixture counteracts the enhancement of oxidative stress induced by consumption of fish oil. Design: A randomised double-blind crossover dietary intervention. Setting: Hugh Sinclair Unit of Human Nutrition, School of Food Biosciences, The University of Reading, Whiteknights PO Box 226, Reading RG6 6AP, UK. Subjects and intervention: A total of 32 free-living healthy nonsmoking volunteers were recruited by posters and e-mails in The University of Reading. One volunteer withdrew during the study. The volunteers consumed a daily supplement comprising capsules containing fish oil (4 x 1 g) or fish oil (4 x 1 g) containing a natural carotenoid mixture (4 x 7.6 mg) for 3 weeks in a randomised crossover design separated by a 12 week washout phase. The carotenoid mixture provided a daily intake of beta-carotene (6.0 mg), alpha-carotene (1.4 mg), lycopene (4.5 mg), bixin (11.7 mg), lutein (4.4 mg) and paprika carotenoids (2.2 mg). Blood and urine samples were collected on days 0 and 21 of each dietary period. Results: The carotenoid mixture reduced the fall in ex vivo oxidative stability of low-density lipoprotein (LDL) induced by the fish oil (P = 0.045) and it reduced the extent of DNA damage assessed by the concentration of 8-hydroxy-2'-deoxyguanosine in urine (P = 0.005). There was no effect on the oxidative stability of plasma ex vivo assessed by the oxygen radical absorbance capacity test. beta- Carotene, alpha-carotene, lycopene and lutein were increased in the plasma of subjects consuming the carotenoid mixture. Plasma triglyceride levels were reduced significantly more than the reduction for the fish oil control (P = 0.035), but total cholesterol, HDL and LDL levels were not significantly changed by the consumption of the carotenoid mixture. Conclusions: Consumption of the natural carotenoid mixture lowered the increase in oxidative stress induced by the fish oil as assessed by ex vivo oxidative stability of LDL and DNA degradation product in urine. The carotenoid mixture also enhanced the plasma triglyceride-lowering effect of the fish oil.

Chemical, physical, and sensory properties of dairy products enriched with conjugated linoleic acid

Recent studies have illustrated the effects of cis-9, trans-11 conjugated linoleic acid (CLA) on human health. Ruminant-derived meat, milk and dairy products are the predominant sources of cis-9, trans-11 CLA in the human diet. This study evaluated the processing properties, texture, storage characteristics, and organoleptic properties of UHT milk, Caerphilly cheese, and butter produced from a milk enriched to a level of cis-9, trans-11 CLA that has been shown to have biological effects in humans. Forty-nine early-lactation Holstein-British Friesian cows were fed total mixed rations containing 0 (control) or 45 g/kg ( on dry matter basis) of a mixture (1:2 wt/wt) of fish oil and sunflower oil during two consecutive 7-d periods to produce a control and CLA-enhanced milk, respectively. Milk produced from cows fed the control and fish and sunflower oil diets contained 0.54 and 4.68 g of total CLA/100 g of fatty acids, respectively. Enrichment of CLA in raw milk from the fish and sunflower oil diet was also accompanied by substantial increases in trans C18:1 levels, lowered C18: 0, cis-C18:1, and total saturated fatty acid concentrations, and small increases in n-3 polyunsaturated fatty acid content. The CLA-enriched milk was used for the manufacture of UHT milk, butter, and cheese. Both the CLA-enhanced butter and cheese were less firm than control products. Although the sensory profiles of the CLA-enriched milk, butter, and cheese differed from those of the control products with respect to some attributes, the overall impression and flavor did not differ. In conclusion, it is feasible to produce CLA-enriched dairy products with acceptable storage and sensory characteristics.

Influence of apolipoprotein E genotype and dietary alpha-tocopherol on redox status and C-reactive protein levels in apolipoprotein E3 and E4 targeted replacement mice

The molecular basis of the positive association between apoE4 genotype and CVD remains unclear. There is direct in vitro evidence indicating that apoE4 is a poorer antioxidant relative to the apoE3 isoform, with some indirect in vivo evidence also available. Therefore it was hypothesised that apoE4 carriers may benefit from alpha-tocopherol (alpha-Toc) supplementation. Targeted replacement mice expressing the human apoE3 and apoE4 were fed with a diet poor (0 mg/kg diet) or rich (200 mg/kg diet) in alpha-Toc for 12 weeks. Neither apoE genotype nor dietary alpha-Toc exerted any effects on the antioxidant defence system, including glutathione, catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase activities. In addition, no differences were observed in mitogen-induced lymphocyte proliferation. alpha-Toc concentrations were modestly higher in plasma and lower in tissues of apoE4 compared with apoE3 mice, with the greatest differences evident in the lung, suggesting that an apoE4 genotype may reduce alpha-Toc delivery to tissues. A tendency towards increased plasma F-2-isoprostanes in apoE4 mice was observed, while liver thiobarbituric acid-reactive substances did not differ between apoE3 and apoE4 mice. In addition, C-reactive protein (CRP) concentrations were reduced in apoE4 mice indicating that this positive effect on CRP may in part negate the increased CVD risk associated with an apoE4 genotype.