Colonic Health: Fermentation and Short Chain Fatty Acids Wong, Julia M. W; de Souza, Russell; Kendall, Cyril W. C ...
Journal of clinical gastroenterology,
2006-March, Letnik:
40, Številka:
3
Journal Article, Conference Proceeding
Recenzirano
Interest has been recently rekindled in short chain fatty acids (SCFAs) with the emergence of prebiotics and probiotics aimed at improving colonic and systemic health. Dietary carbohydrates, ...specifically resistant starches and dietary fiber, are substrates for fermentation that produce SCFAs, primarily acetate, propionate, and butyrate, as end products. The rate and amount of SCFA production depends on the species and amounts of microflora present in the colon, the substrate source and gut transit time. SCFAs are readily absorbed. Butyrate is the major energy source for colonocytes. Propionate is largely taken up by the liver. Acetate enters the peripheral circulation to be metabolized by peripheral tissues. Specific SCFA may reduce the risk of developing gastrointestinal disorders, cancer, and cardiovascular disease. Acetate is the principal SCFA in the colon, and after absorption it has been shown to increase cholesterol synthesis. However, propionate, a gluconeogenerator, has been shown to inhibit cholesterol synthesis. Therefore, substrates that can decrease the acetatepropionate ratio may reduce serum lipids and possibly cardiovascular disease risk. Butyrate has been studied for its role in nourishing the colonic mucosa and in the prevention of cancer of the colon, by promoting cell differentiation, cell-cycle arrest and apoptosis of transformed colonocytes; inhibiting the enzyme histone deacetylase and decreasing the transformation of primary to secondary bile acids as a result of colonic acidification. Therefore, a greater increase in SCFA production and potentially a greater delivery of SCFA, specifically butyrate, to the distal colon may result in a protective effect. Butyrate irrigation (enema) has also been suggested in the treatment of colitis. More human studies are now needed, especially, given the diverse nature of carbohydrate substrates and the SCFA patterns resulting from their fermentation. Short-term and long-term human studies are particularly required on SCFAs in relation to markers of cancer risk. These studies will be key to the success of dietary recommendations to maximize colonic disease prevention.
Aims/hypothesis Dietary non-oil-seed pulses (chickpeas, beans, peas, lentils, etc.) are a good source of slowly digestible carbohydrate, fibre and vegetable protein and a valuable means of lowering ...the glycaemic-index (GI) of the diet. To assess the evidence that dietary pulses may benefit glycaemic control, we conducted a systematic review and meta-analysis of randomised controlled experimental trials investigating the effect of pulses, alone or as part of low-GI or high-fibre diets, on markers of glycaemic control in people with and without diabetes. Methods We searched MEDLINE, EMBASE, CINAHL, and the Cochrane Library for relevant controlled trials of >=7 days. Two independent reviewers (A. Esfahani and J. M. W. Wong) extracted information on study design, participants, treatments and outcomes. Data were pooled using the generic inverse variance method and expressed as standardised mean differences (SMD) with 95% CIs. Heterogeneity was assessed by χ ² and quantified by I ². Meta-regression models identified independent predictors of effects. Results A total of 41 trials (39 reports) were included. Pulses alone (11 trials) lowered fasting blood glucose (FBG) (-0.82, 95% CI -1.36 to -0.27) and insulin (-0.49, 95% CI -0.93 to -0.04). Pulses in low-GI diets (19 trials) lowered glycosylated blood proteins (GP), measured as HbA₁c or fructosamine (-0.28, 95% CI -0.42 to -0.14). Finally, pulses in high-fibre diets (11 trials) lowered FBG (-0.32, 95% CI -0.49 to -0.15) and GP (-0.27, 95% CI -0.45 to -0.09). Inter-study heterogeneity was high and unexplained for most outcomes, with benefits modified or predicted by diabetes status, pulse type, dose, physical form, duration of follow-up, study quality, macronutrient profile of background diets, feeding control and design. Conclusions/interpretation Pooled analyses demonstrated that pulses, alone or in low-GI or high-fibre diets, improve markers of longer term glycaemic control in humans, with the extent of the improvements subject to significant inter-study heterogeneity. There is a need for further large, well-designed trials.
Abstract
Primary human hepatocytes (PHHs) are commonly used for in vitro studies of drug-induced liver injury. However, when cultured as 2D monolayers, PHH lose crucial hepatic functions within ...hours. This dedifferentiation can be ameliorated when PHHs are cultured in sandwich configuration (2Dsw), particularly when cultures are regularly re-overlaid with extracellular matrix, or as 3D spheroids. In this study, the 6 participating laboratories evaluated the robustness of these 2 model systems made from cryopreserved PHH from the same donors considering both inter-donor and inter-laboratory variability and compared their suitability for use in repeated-dose toxicity studies using 5 different hepatotoxins with different toxicity mechanisms. We found that expression levels of proteins involved in drug absorption, distribution, metabolism, and excretion, as well as catalytic activities of 5 different CYPs, were significantly higher in 3D spheroid cultures, potentially affecting the exposure of the cells to drugs and their metabolites. Furthermore, global proteomic analyses revealed that PHH in 3D spheroid configuration were temporally stable whereas proteomes from the same donors in 2Dsw cultures showed substantial alterations in protein expression patterns over the 14 days in culture. Overall, spheroid cultures were more sensitive to the hepatotoxic compounds investigated, particularly upon long-term exposures, across testing sites with little inter-laboratory or inter-donor variability. The data presented here suggest that repeated-dosing regimens improve the predictivity of in vitro toxicity assays, and that PHH spheroids provide a sensitive and robust system for long-term mechanistic studies of drug-induced hepatotoxicity, whereas the 2Dsw system has a more dedifferentiated phenotype and lower sensitivity to detect hepatotoxicity.
There is a history of interest in the metabolic effects of alterations in small intestinal digestion and colonic fermentation of carbohydrate. It is believed that the rate of digestion of ...carbohydrate determines the place and form in which carbohydrate is absorbed. Slowly absorbed or lente carbohydrate sources may reduce postprandial glucose surges and the need for insulin with important implications for lowering coronary heart disease risk and reducing diabetes incidence. Carbohydrates that are not digested in the small intestine will enter the colon, and those that are fermentable will be salvaged as short-chain fatty acids in the colon and at the same time may stimulate colonic microflora, such as bifidobacteria. This process may have metabolic effects in the gut and throughout the host, possibly related to short-chain fatty acid products, although these effects are less well documented. One important aspect of colonic fermentation is the stimulation of certain populations of the colonic microflora, which may assist in the biotransformation of bioactive food components including the cleaving of plant phenolics from their glycone to produce the more rapidly absorbed aglycone. However, human studies have been limited. Therefore, further studies are required to explore these important aspects of metabolism related to the rate of carbohydrate absorption and fermentation and their implications in health and disease.
The UV RESISTANCE LOCUS 8 (UVR8) photoreceptor specifically mediates photomorphogenic responses to UV‐B. Photoreception induces dissociation of dimeric UVR8 into monomers to initiate responses. ...However, the regulation of dimer/monomer status in plants growing under photoperiodic conditions has not been examined. Here we show that UVR8 establishes a dimer/monomer photo‐equilibrium in plants growing in diurnal photoperiods in both controlled environments and natural daylight. The photo‐equilibrium is determined by the relative rates of photoreception and dark‐reversion to the dimer. Experiments with mutants in REPRESSOR OF UV‐B PHOTOMORPHOGENESIS 1 (RUP1) and RUP2 show that these proteins are crucial in regulating the photo‐equilibrium because they promote reversion to the dimer. In plants growing in daylight, the UVR8 photo‐equilibrium is most strongly correlated with low ambient fluence rates of UV‐B (up to 1.5 μmol m−2 s−1), rather than higher fluence rates or the amount of photosynthetically active radiation. In addition, the rate of reversion of monomer to dimer is reduced at lower temperatures, promoting an increase in the relative level of monomer at approximately 8–10 °C. Thus, UVR8 does not behave like a simple UV‐B switch under photoperiodic growth conditions but establishes a dimer/monomer photo‐equilibrium that is regulated by UV‐B and also influenced by temperature.
UV‐B absorption by the photoreceptor UVR8 induces dimer dissociation, forming monomers that initiate photomorphogenic UV‐B responses. However, the regulation of dimer/monomer status in plants growing under photoperiodic conditions has not been examined. Here we show that UVR8 does not behave like a simple UV‐B switch under photoperiodic conditions in both controlled environments and natural daylight, but establishes a dimer/monomer photo‐equilibrium that is regulated by UV‐B and influenced by temperature.
We present the distributions of hydrographic properties (potential temperature, salinity, dissolved oxygen, and micromolar level inorganic macronutrients) along two sections occupied in the ...subtropical North Atlantic as part of the first U.S. GEOTRACES (GA03) survey during 2010 and 2011. The purpose of this work is to place subsequent papers in this special issue in a general context and to provide a framework in which the observed distributions of Trace Elements and Isotopes can be interpreted. Using these hydrographic properties we use a modified Optimum Multiparameter water mass analysis method to diagnose the relative contributions of various water types along the sections and rationalize their distributions. The water mass compositions appear largely consistent with what is understood from previous studies about the large scale circulation and ventilation of the North Atlantic, with perhaps one exception. We found that the North Atlantic Deep water both east and west of the Mid Atlantic Ridge is more strongly influenced by Iceland Scotland Overflow Water relative to Denmark Straits Overflow Water (about 3:1) than inferred from other tracer studies (typically 2:1). It remains unclear whether this is an artifact of our calculation or a real change in deep water composition in the decades between the determinations.
Aims/hypothesis Fenofibrate caused an acute, sustained plasma creatinine increase in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) and Action to Control Cardiovascular Risk in ...Diabetes (ACCORD) studies. We assessed fenofibrate's renal effects overall and in a FIELD washout sub-study. Methods Type 2 diabetic patients (n = 9,795) aged 50 to 75 years were randomly assigned to fenofibrate (n = 4,895) or placebo (n = 4,900) for 5 years, after 6 weeks fenofibrate run-in. Albuminuria (urinary albumin/creatinine ratio measured at baseline, year 2 and close-out) and estimated GFR, measured four to six monthly according to the Modification of Diet in Renal Disease Study, were pre-specified endpoints. Plasma creatinine was re-measured 8 weeks after treatment cessation at close-out (washout sub-study, n = 661). Analysis was by intention-to-treat. Results During fenofibrate run-in, plasma creatinine increased by 10.0 μmol/l (p < 0.001), but quickly reversed on placebo assignment. It remained higher on fenofibrate than on placebo, but the chronic rise was slower (1.62 vs 1.89 μmol/l annually, p = 0.01), with less estimated GFR loss (1.19 vs 2.03 ml min⁻¹ 1.73 m⁻² annually, p < 0.001). After washout, estimated GFR had fallen less from baseline on fenofibrate (1.9 ml min⁻¹ 1.73 m⁻², p = 0.065) than on placebo (6.9 ml min⁻¹ 1.73 m⁻², p < 0.001), sparing 5.0 ml min⁻¹ 1.73 m⁻² (95% CI 2.3-7.7, p < 0.001). Greater preservation of estimated GFR with fenofibrate was observed with baseline hypertriacylglycerolaemia (n = 169 vs 491 without) alone, or combined with low HDL-cholesterol (n = 140 vs 520 without) and reductions of ≥0.48 mmol/l in triacylglycerol over the active run-in period (pre-randomisation) (n = 356 vs 303 without). Fenofibrate reduced urine albumin concentrations and hence albumin/creatinine ratio by 24% vs 11% (p < 0.001; mean difference 14% 95% CI 9-18; p < 0.001), with 14% less progression and 18% more albuminuria regression (p < 0.001) than in participants on placebo. End-stage renal event frequency was similar (n = 21 vs 26, p = 0.48). Conclusions/interpretation Fenofibrate reduced albuminuria and slowed estimated GFR loss over 5 years, despite initially and reversibly increasing plasma creatinine. Fenofibrate may delay albuminuria and GFR impairment in type 2 diabetes patients. Confirmatory studies are merited. Trial registration ISRCTN64783481 Funding The study was funded by grants from Laboratoires Fournier SA (Dijon, France; now part of Abbott Pharmaceuticals) and the National Health and Medical Research Council, Australia
BACKGROUND: Cholesterol-lowering foods may be more effective when consumed as combinations rather than as single foods. OBJECTIVES: Our aims were to determine the effectiveness of consuming a ...combination of cholesterol-lowering foods (dietary portfolio) under real-world conditions and to compare these results with published data from the same participants who had undergone 4-wk metabolic studies to compare the same dietary portfolio with the effects of a statin. DESIGN: For 12 mo, 66 hyperlipidemic participants were prescribed diets high in plant sterols (1.0 g/1000 kcal), soy protein (22.5 g/1000 kcal), viscous fibers (10 g/1000 kcal), and almonds (23 g/1000 kcal). Fifty-five participants completed the 1-y study. The 1-y data were also compared with published results on 29 of the participants who had also undergone separate 1-mo metabolic trials of a diet and a statin. RESULTS: At 3 mo and 1 y, mean (±SE) LDL-cholesterol reductions appeared stable at 14.0 ± 1.6% (P < 0.001) and 12.8 ± 2.0% (P < 0.001), respectively (n = 66). These reductions were less than those observed after the 1-mo metabolic diet and statin trials. Nevertheless, 31.8% of the participants (n = 21 of 66) had LDL-cholesterol reductions of >20% at 1 y (x ± SE: -29.7 ± 1.6%). The LDL-cholesterol reductions in this group were not significantly different from those seen after their respective metabolically controlled portfolio or statin treatments. A correlation was found between total dietary adherence and LDL-cholesterol change (r = -0.42, P < 0.001). Only 2 of the 26 participants with <55% compliance achieved LDL-cholesterol reductions >20% at 1 y. CONCLUSIONS: More than 30% of motivated participants who ate the dietary portfolio of cholesterol-lowering foods under real-world conditions were able to lower LDL-cholesterol concentrations >20%, which was not significantly different from their response to a first-generation statin taken under metabolically controlled conditions.
Optical pacing (OP) uses pulsed infrared light to initiate heartbeats in electrically excitable cardiac tissues without employing exogenous agents. OP is an alternative approach to electrical pacing ...that may overcome some its disadvantages for some applications. In this review, we discuss the initial demonstrations, mechanisms, safety, advantages and applications of OP.
CONTEXT To enhance the effectiveness of diet in lowering cholesterol, recommendations
of the Adult Treatment Panel III of the National Cholesterol Education Program
emphasize diets low in saturated ...fat together with plant sterols and viscous
fibers, and the American Heart Association supports the use of soy protein
and nuts. OBJECTIVE To determine whether a diet containing all of these recommended food
components leads to cholesterol reduction comparable with that of 3-hydroxy-3-methylglutaryl
coenzyme A reductase inhibitors (statins). DESIGN Randomized controlled trial conducted between October and December 2002. SETTING AND PARTICIPANTS Forty-six healthy, hyperlipidemic adults (25 men and 21 postmenopausal
women) with a mean (SE) age of 59 (1) years and body mass index of 27.6 (0.5),
recruited from a Canadian hospital-affiliated nutrition research center and
the community. INTERVENTIONS Participants were randomly assigned to undergo 1 of 3 interventions
on an outpatient basis for 1 month: a diet very low in saturated fat, based
on milled whole-wheat cereals and low-fat dairy foods (n = 16; control); the
same diet plus lovastatin, 20 mg/d (n = 14); or a diet high in plant sterols
(1.0 g/1000 kcal), soy protein (21.4 g/1000 kcal), viscous fibers (9.8 g/1000
kcal), and almonds (14 g/1000 kcal) (n = 16; dietary portfolio). MAIN OUTCOME MEASURES Lipid and C-reactive protein levels, obtained from fasting blood samples;
blood pressure; and body weight; measured at weeks 0, 2, and 4 and compared
among the 3 treatment groups. RESULTS The control, statin, and dietary portfolio groups had mean (SE) decreases
in low-density lipoprotein cholesterol of 8.0% (2.1%) (P = .002), 30.9% (3.6%) (P<.001), and 28.6%
(3.2%) (P<.001), respectively. Respective reductions
in C-reactive protein were 10.0% (8.6%) (P = .27),
33.3% (8.3%) (P = .002), and 28.2% (10.8%) (P = .02). The significant reductions in the statin and
dietary portfolio groups were all significantly different from changes in
the control group. There were no significant differences in efficacy between
the statin and dietary portfolio treatments. CONCLUSION In this study, diversifying cholesterol-lowering components in the same
dietary portfolio increased the effectiveness of diet as a treatment of hypercholesterolemia.
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