Effect of 12 wk of resistant starch supplementation on cardiometabolic risk factors in adults with prediabetes: a randomized controlled trial.

Background: Type 2 resistant starch (RS2) has been shown to improve glycemic control and some cardiovascular endpoints in rodent and human studies. Objective: The aim of this study was to perform one of the first randomized clinical trials in adults with prediabetes and one of the longest trials to test whether RS2 can improve cardiometabolic health. Design: 68 overweight [body mass index (BMI) ≥27 kg/m2] adults aged 35-75 y with prediabetes were randomized to consume 45 g/d of high-amylose maize (RS2) or an isocaloric amount of the rapidly digestible starch amylopectin (control) for 12 wk. At baseline and postintervention, ectopic fat depots (visceral adipose tissue, intrahepatic lipids, and intramyocellular lipids) were measured by magnetic resonance imaging/spectroscopy, energy metabolism by respiratory chamber, and carbohydrate metabolism by glycated hemoglobin (HbA1c), an intravenous glucose tolerance test, and a meal tolerance test. Cardiovascular risk factors-serum lipids, blood pressure, heart rate, and inflammatory markers (high-sensitivity C-reactive protein [hs-CRP], interleukin-6, and tumor necrosis factor [TNF]-α)-were also measured. The primary endpoints were insulin sensitivity, insulin secretion, ectopic fat, and markers of inflammation. Data were primarily analyzed as treatment effects via a linear mixed model both with and without the addition of covariates. Results: Relative to the control group, RS2 lowered HbA1c by a clinically insignificant 0.1 ± 0.2% (Δ = -1 ± 2 mmol/mol; P = 0.05) but did not affect insulin secretion, insulin sensitivity, the disposition index, or glucose or insulin areas under the curve relative to baseline (P ≥ 0.23). RS2 decreased heart rate by 5 ± 9 beats/min (P = 0.02) and TNF-α concentrations by 2.1 ± 2.7 pg/mL (P = 0.004), relative to the control group. Ectopic fat, energy expenditure, substrate oxidation, and all other cardiovascular risk factors were unaffected (P ≥ 0.06). Conclusions: 12 wk of supplementation with resistant starch reduced the inflammatory marker TNF-α and heart rate, but it did not significantly improve glycemic control and other cardiovascular disease risk factors, in adults with prediabetes. This trial was registered at clinicaltrials.gov as NCT01708694.

Role of resistant starch on diabetes risk factors in people with prediabetes: Design, conduct, and baseline results of the STARCH trial.

Dietary resistant starch (RS) might alter gastrointestinal tract function in a manner that improves human health, particularly among adults at risk for diabetes. Here, we report the design and baseline results (with emphasis on race differences) from the STARCH trial, the first comprehensive metabolic phenotyping of people with prediabetes enrolled in a randomized clinical trial testing the effect of RS on risk factors for diabetes. Overweight/obese participants (BMI≥27kg/m2 and weight≤143kg), age 35-75y, with confirmed prediabetes were eligible. Participants were randomized to consume 45g/day of RS (RS=amylose) or amylopectin (Control) for 12weeks. The study was designed to evaluate the effect of RS on insulin sensitivity and secretion, ectopic fat, and inflammatory markers. Secondary outcomes included energy expenditure, substrate oxidation, appetite, food intake, colonic microbial composition, fecal and plasma levels of short-chain fatty acids, fecal RS excretion, and gut permeability. Out of 280 individuals screened, 68 were randomized, 65 started the intervention, and 63 were analyzed at baseline (mean age 55y, BMI 35.6kg/m2); 2 were excluded from baseline analyses due to abnormal insulin and diabetes. Sex and race comparisons at baseline were reported. African-Americans had higher baseline acute insulin response to glucose (AIRg measured by frequently sampled intravenous glucose tolerance test) compared to Caucasians, despite having less visceral adipose tissue mass and intrahepatic lipid; all other glycemic variables were similar between races. Sleep energy expenditure was ~90-100kcal/day lower in African-Americans after adjusting for insulin sensitivity and secretion. This manuscript provides an overview of the strategy used to enroll people with prediabetes into the STARCH trial and describes methodologies used in the assessment of risk factors for diabetes. Clinicaltrials.gov identifier: STARCH (NCT01708694). The present study reference can be found here: https://clinicaltrials.gov/ct2/show/NCT01708694. Submission Category: "Study Design, Statistical Design, Study Protocols".

Obese ZDF rats fermented resistant starch with effects on gut microbiota but no reduction in abdominal fat.

SCOPE: To determine if whole-grain (WG) flour with resistant starch (RS) will produce greater fermentation than isolated RS in obese Zucker Diabetic Fatty (ZDF) rats, and whether greater fermentation results in different microbiota, reduced abdominal fat, and increased insulin sensitivity. METHODS AND RESULTS: This study utilized four groups fed diets made with either isolated digestible control starch, WG control flour (6.9% RS), isolated RS-rich corn starch (25% RS), or WG corn flour (25% RS). ZDF rats fermented RS and RS-rich WG flour to greatest extent among groups. High-RS groups had increased serum glucagon-like peptide 1 (GLP-1) active. Feeding isolated RS showed greater Bacteroidetes to Firmicutes phyla among groups, and rats consuming low RS diets possessed more bacteria in Lactobacillus genus. However, no differences in abdominal fat were observed, but rats with isolated RS had greatest insulin sensitivity among groups. CONCLUSIONS: Data demonstrated ZDF rats (i) possess a microbiota that fermented RS, and (ii) WG high-RS fermented better than purified RS. However, fermentation and microbiota changes did not translate into reduced abdominal fat. The defective leptin receptor may limit ZDF rats from responding to increased GLP-1 and different microbiota for reducing abdominal fat, but did not prevent improved insulin sensitivity.

Simultaneous delivery of antibiotics neomycin and ampicillin in drinking water inhibits fermentation of resistant starch in rats.

SCOPE: Antibiotics ampicillin 1 g/L and neomycin 0.5 g/L were added to drinking water before or during feeding of resistant starch (RS) to rats to inhibit fermentation. METHODS AND RESULTS: In a preliminary study, antibiotics and no RS were given prior to rats receiving a transplant of cecal contents via gavage from donor rats fed RS (without antibiotics) or a water gavage before feeding resistant starch to both groups. Antibiotics given prior to feeding RS did not prevent later fermentation of RS regardless of either type of gavage. In the second study, antibiotics were given simultaneously with feeding of RS. This resulted in inhibition of fermentation of RS with cecal contents pH >8 and low amounts of acetate and butyrate. Rats treated with antibiotics had reduced Bifidobacteria spp., but similar Bacteroides spp. to control groups to reduce acetate and butyrate and preserve the production of propionate. Despite reduced fermentation, rats given antibiotics had increased glucagon-like peptide 1 (GLP-1) and cecum size, measures that are usually associated with fermentation. CONCLUSIONS: A simultaneous delivery of antibiotics inhibited fermentation of RS. However, increased GLP-1 and cecum size would be confounding effects in assessing the mechanism for beneficial effects of dietary RS by knocking out fermentation.

Pomegranate juice and extract extended lifespan and reduced intestinal fat deposition in Caenorhabditis elegans.

Pomegranate juice with a high content of polyphenols, pomegranate extract, ellagic acid, and urolithin A, have anti-oxidant and anti-obesity effects in humans. Pomegranate juice extends lifespan of Drosophila melanogaster. Caenorhabditis elegans (C. elegans) (n = 6) compared to the control group in each treatment, lifespan was increased by pomegranate juice in wild type (N2, 56 %, P < 0.001) and daf-16 mutant (daf-16(mgDf50)I) (18 %, P = 0.00012), by pomegranate extract in N2 (28 %, P = 0.00004) and in daf-16(mgDf50)I (10 %, P < 0.05), or by ellagic acid (11 %, P < 0.05). Pomegranate juice reduced intestinal fat deposition (IFD) in C. elegans (n = 10) N2 (-68 %, P = 0.0003) or in the daf-16(mgDf50)I (-33 %, P = 0.0034). The intestinal fat deposition was increased by pomegranate extract in N2 (137 %, P < 0.0138) and in daf-16(mgDf50)I (26 %, P = 0.0225), by ellagic acid in N2 (66 %, P < 0.0001) and in daf-16(mgDf50)I (74 %, P < 0.0001), or by urolithin A in N2 (57 %, P = 0.0039) and in daf-16(mgDf50)I (43 %, P = 0.0001). These effects were partially mediated by the daf-16 pathway. The data may offer insights to human aging and obesity due to homology with C. elegans.

Impact of Different Fecal Processing Methods on Assessments of Bacterial Diversity in the Human Intestine.

The intestinal microbiota are integral to understanding the relationships between nutrition and health. Therefore, fecal sampling and processing protocols for metagenomic surveys should be sufficiently robust, accurate, and reliable to identify the microorganisms present. We investigated the use of different fecal preparation methods on the bacterial community structures identified in human stools. Complete stools were collected from six healthy individuals and processed according to the following methods: (i) randomly sampled fresh stool, (ii) fresh stool homogenized in a blender for 2 min, (iii) randomly sampled frozen stool, and (iv) frozen stool homogenized in a blender for 2 min, or (v) homogenized in a pneumatic mixer for either 10, 20, or 30 min. High-throughput DNA sequencing of the 16S rRNA V4 regions of bacterial community DNA extracted from the stools showed that the fecal microbiota remained distinct between individuals, independent of processing method. Moreover, the different stool preparation approaches did not alter intra-individual bacterial diversity. Distinctions were found at the level of individual taxa, however. Stools that were frozen and then homogenized tended to have higher proportions of Faecalibacterium, Streptococcus, and Bifidobacterium and decreased quantities of Oscillospira, Bacteroides, and Parabacteroides compared to stools that were collected in small quantities and not mixed prior to DNA extraction. These findings indicate that certain taxa are at particular risk for under or over sampling due to protocol differences. Importantly, homogenization by any method significantly reduced the intra-individual variation in bacteria detected per stool. Our results confirm the robustness of fecal homogenization for microbial analyses and underscore the value of collecting and mixing large stool sample quantities in human nutrition intervention studies.

Obese Mice Fed a Diet Supplemented with Enzyme-Treated Wheat Bran Display Marked Shifts in the Liver Metabolome Concurrent with Altered Gut Bacteria.

BACKGROUND: Enzyme-treated wheat bran (ETWB) contains a fermentable dietary fiber previously shown to decrease liver triglycerides (TGs) and modify the gut microbiome in mice. It is not clear which mechanisms explain how ETWB feeding affects hepatic metabolism, but factors (i.e., xenometabolites) associated with specific microbes may be involved. OBJECTIVE: The objective of this study was to characterize ETWB-driven shifts in the cecal microbiome and to identify correlates between microbial changes and diet-related differences in liver metabolism in diet-induced obese mice that typically display steatosis. METHODS: Five-week-old male C57BL/6J mice fed a 45%-lard-based fat diet supplemented with ETWB (20% wt:wt) or rapidly digestible starch (control) (n = 15/group) for 10 wk were characterized by using a multi-omics approach. Multivariate statistical analysis was used to identify variables that were strong discriminators between the ETWB and control groups. RESULTS: Body weight and liver TGs were decreased by ETWB feeding (by 10% and 25%, respectively; P < 0.001), and an index of liver reactive oxygen species was increased (by 29%; P < 0.01). The cecal microbiome showed an increase in Bacteroidetes (by 42%; P < 0.05) and a decrease in Firmicutes (by 16%; P < 0.05). Metabolites that were strong discriminators between the ETWB and control groups included decreased liver antioxidants (glutathione and α-tocopherol); decreased liver carbohydrate metabolites, including glucose; lower hepatic arachidonic acid; and increased liver and plasma ß-hydroxybutyrate. Liver transcriptomics revealed key metabolic pathways affected by ETWB, especially those related to lipid metabolism and some fed- or fasting-regulated genes. CONCLUSIONS: Together, these changes indicate that dietary fibers such as ETWB regulate hepatic metabolism concurrently with specific gut bacteria community shifts in C57BL/6J mice. It is proposed that these changes may elicit gut-derived signals that reach the liver via enterohepatic circulation, ultimately affecting host liver metabolism in a manner that mimics, in part, the fasting state.

Mice Fed a High-Fat Diet Supplemented with Resistant Starch Display Marked Shifts in the Liver Metabolome Concurrent with Altered Gut Bacteria.

BACKGROUND: High-amylose-maize resistant starch type 2 (HAMRS2) is a fermentable dietary fiber known to alter the gut milieu, including the gut microbiota, which may explain the reported effects of resistant starch to ameliorate obesity-associated metabolic dysfunction. OBJECTIVE: Our working hypothesis was that HAMRS2-induced microbiome changes alter gut-derived signals (i.e., xenometabolites) reaching the liver via the portal circulation, in turn altering liver metabolism by regulating gene expression and other pathways. METHODS: We used a multi-omics systems biology approach to characterize HAMRS2-driven shifts to the cecal microbiome, liver metabolome, and transcriptome, identifying correlates between microbial changes and liver metabolites under obesogenic conditions that, to our knowledge, have not previously been recognized. Five-week-old male C57BL/6J mice were fed an energy-dense 45% lard-based-fat diet for 10 wk supplemented with either 20% HAMRS2 by weight (n = 14) or rapidly digestible starch (control diet; n = 15). RESULTS: Despite no differences in food intake, body weight, glucose tolerance, fasting plasma insulin, or liver triglycerides, the HAMRS2 mice showed a 15-58% reduction in all measured liver amino acids, except for Gln, compared with control mice. These metabolites were equivalent in the plasma of HAMRS2 mice compared with controls, and transcripts encoding key amino acid transporters were not different in the small intestine or liver, suggesting that HAMRS2 effects were not simply due to lower hepatocyte exposure to systemic amino acids. Instead, alterations in gut microbial metabolism could have affected host nitrogen and amino acid homeostasis: HAMRS2 mice showed a 62% increase (P < 0.0001) in 48-h fecal output and a 41% increase (P < 0.0001) in fecal nitrogen compared with control mice. Beyond amino acid metabolism, liver transcriptomics revealed pathways related to lipid and xenobiotic metabolism; and pathways related to cell proliferation, differentiation, and growth were affected by HAMRS2 feeding. CONCLUSION: Together, these differences indicate that HAMRS2 dramatically alters hepatic metabolism and gene expression concurrent with shifts in specific gut bacteria in C57BL/6J mice.

Resistant starch alters gut microbiome and metabolomic profiles concurrent with amelioration of chronic kidney disease in rats.

Patients and animals with chronic kidney disease (CKD) exhibit profound alterations in the gut environment including shifts in microbial composition, increased fecal pH, and increased blood levels of gut microbe-derived metabolites (xenometabolites). The fermentable dietary fiber high amylose maize-resistant starch type 2 (HAMRS2) has been shown to alter the gut milieu and in CKD rat models leads to markedly improved kidney function. The aim of the present study was to identify specific cecal bacteria and cecal, blood, and urinary metabolites that associate with changes in kidney function to identify potential mechanisms involved with CKD amelioration in response to dietary resistant starch. Male Sprague-Dawley rats with adenine-induced CKD were fed a semipurified low-fiber diet or a high-fiber diet [59% (wt/wt) HAMRS2] for 3 wk (n = 9 rats/group). The cecal microbiome was characterized, and cecal contents, serum, and urine metabolites were analyzed. HAMRS2-fed rats displayed decreased cecal pH, decreased microbial diversity, and an increased Bacteroidetes-to-Firmicutes ratio. Several uremic retention solutes were altered in the cecal contents, serum, and urine, many of which had strong correlations with specific gut bacteria abundances, i.e., serum and urine indoxyl sulfate were reduced by 36% and 66%, respectively, in HAMRS2-fed rats and urine p-cresol was reduced by 47% in HAMRS2-fed rats. Outcomes from this study were coincident with improvements in kidney function indexes and amelioration of CKD outcomes previously reported for these rats, suggesting an important role for microbial-derived factors and gut microbe metabolism in regulating host kidney function.

Impact of Dietary Fibers on Nutrient Management and Detoxification Organs: Gut, Liver, and Kidneys.

Increased dietary fiber (DF) intake elicits a wide range of physiologic effects, not just locally in the gut, but systemically. DFs can greatly alter the gut milieu by affecting the gut microbiome, which in turn influences the gut barrier, gastrointestinal immune and endocrine responses, and nitrogen cycling and microbial metabolism. These gut-associated changes can then alter the physiology and biochemistry of the body's other main nutrient management and detoxification organs, the liver and kidneys. The molecular mechanisms by which DF alters the physiology of the gut, liver, and kidneys is likely through gut-localized events (i.e., bacterial nitrogen metabolism, microbe-microbe, and microbe-host cell interactions) coupled with specific factors that emanate from the gut in response to DF, which signal to or affect the physiology of the liver and kidneys. The latter may include microbe-derived xenometabolites, peptides, or bioactive food components made available by gut microbes, inflammation signals, and gut hormones. The intent of this review is to summarize how DF alters the gut milieu to specifically affect intestinal, liver, and kidney functions and to discuss the potential local and systemic signaling networks that are involved.

Using Caenorhabditis elegans as a Model for Obesity Pharmacology Development.

The Caenorhabditis elegans model is a rapid and inexpensive method to address pharmacologic questions. We describe the use of C. elegans to explore 2 pharmacologic questions concerning candidate antiobesity drugs and illustrate its potential usefulness in pharmacologic research: (1) to determine a ratio of betahistine-olanzapine that blocks the olanzapine-induced intestinal fat deposition (IFD) as detected by Nile red staining and (2) to identify the mechanism of action of a pharmaceutical candidate AB-101 that reduces IFD. Olanzapine (53 µg/mL) increased the IFD (12.1 ± 0.1%, P < 0.02), which was blocked by betahistine (763 µg/mL, 39.3 ± 0.01%, P < 0.05) in wild-type C. elegans (N2). AB-101 (1.0%) reduced the IFD in N2 (P < 0.05), increased the pharyngeal pumping rate (P < 0.05), and reversed the elevated IFD induced by protease inhibitors atazanavir and ritonavir (P < 0.05). AB-101 did not affect IFD in a ACS null mutant strain acs-4(ok2872) III/hT2[bli-4(e937) let-?(q782) qIs48](I;III) suggesting an involvement of the lipid oxidation pathway and an upregulation of CPT-1. Our studies suggest that C. elegans may be used as a resource in pharmacologic research. This article is intended to stimulate a greater appreciation of its value in the development of new pharmaceutical interventions.

Improving healthspan via changes in gut microbiota and fermentation.

Dietary resistant starch impact on intestinal microbiome and improving healthspan is the topic of this review. In the elderly population, dietary fiber intake is lower than recommended. Dietary resistant starch as a source of fiber produces a profound change in gut microbiota and fermentation in animal models of aging. Dietary resistant starch has the potential for improving healthspan in the elderly through multiple mechanisms as follows: (1) enhancing gut microbiota profile and production of short-chain fatty acids, (2) improving gut barrier function, (3) increasing gut peptides that are important in glucose homeostasis and lipid metabolism, and (4) mimicking many of the effects of caloric restriction including upregulation of genes involved in xenobiotic metabolism.

Oat consumption reduced intestinal fat deposition and improved health span in Caenorhabditis elegans model.

In addition to their fermentable dietary fiber and the soluble ß-glucan fiber, oats have unique avenanthramides that have anti-inflammatory and antioxidant properties that reduce coronary heart disease in human clinical trials. We hypothesized that oat consumption will increase insulin sensitivity, reduce body fat, and improve health span in Caenorhabditis elegans through a mechanism involving the daf-2 gene, which codes for the insulin/insulin-like growth factor-1-like receptor, and that hyperglycemia will attenuate these changes. Caenorhabditis elegans wild type (N2) and the null strains sir-2.1, daf-16, and daf-16/daf-2 were fed Escherichia coli (OP50) and oat flakes (0.5%, 1.0%, or 3%) with and without 2% glucose. Oat feeding decreased intestinal fat deposition in N2, daf-16, or daf-16/daf-2 strains (P < .05); and glucose did not affect intestinal fat deposition response. The N2, daf-16, or sir-2.1 mutant increased the pharyngeal pumping rate (P < .05), a surrogate marker of life span, following oat consumption. Oat consumption increased ckr-1, gcy-8, cpt-1, and cpt-2 mRNA expression in both the N2 and the sir-2.1 mutant, with significantly higher expression in sir-2.1 than in N2 (P < .01). Additional glucose further increased expression 1.5-fold of the 4 genes in N2 (P < .01), decreased the expression of all except cpt-1 in the daf-16 mutant, and reduced mRNA expression of the 4 genes in the daf-16/daf-2 mutant (P < .01). These data suggest that oat consumption reduced fat storage and increased ckr-1, gcy-8, cpt-1, or cpt-2 through the sir-2.1 genetic pathway. Oat consumption may be a beneficial dietary intervention for reducing fat accumulation, augmenting health span, and improving hyperglycemia-impaired lipid metabolism.

Induction of Energy Expenditure by Sitagliptin Is Dependent on GLP-1 Receptor.

Sitagliptin (SG) increases serum GLP-1 (Glucagon-like peptide-1) through inhibition of the hormone degradation. Resistant starch (RS) induces GLP-1 expression by stimulating L-cells in the intestine. Sitagliptin and resistant starch may have a synergistic interaction in the induction of GLP-1. This possibility was tested in current study in a mouse model of type 2 diabetes. Hyperglycemia was induced in the diet-induced obese mice by a signal injection of streptozotocin (STZ). Sitagliptin (0.4g/100g diet) was tested in the mice (n = 55) with dietary RS (HAM-RS2) at three dosages (0, 15, or 28g/100g diet). Energy and glucose metabolism were monitored in the evaluation of synergistic activity, and GLP-1 activity was determined in the GLP-1 receptor knockout (KO) mice. In the wild type mice, body weight and adiposity were reduced by sitagliptin, which was enhanced by RS (28g). Serum GLP-1 was induced and energy expenditure was enhanced by sitagliptin. Fasting glucose, insulin, and leptin levels were decreased by sitagliptin. The sitagliptin effects were lost in the KO mice (n = 25) although induction of serum GLP-1 by sitagliptin was even stronger in KO mice. The data suggests that sitagliptin is able to reduce adiposity and insulin resistance through induction of energy expenditure. The effect of sitagliptin is partially enhanced by RS. GLP-1 receptor may regulate serum GLP-1 by facilitating the hormone clearance.

Role of resistant starch in improving gut health, adiposity, and insulin resistance.

The realization that low-glycemic index diets were formulated using resistant starch led to more than a decade of research on the health effects of resistant starch. Determination of the metabolizable energy of the resistant starch product allowed for the performance of isocaloric studies. Fermentation of resistant starch in rodent studies results in what appears to be a healthier gut, demonstrated by increased amounts of short-chain fatty acids, an apparent positive change in the microbiota, and increased gene expression for gene products involved in normal healthy proliferation and apoptosis of potential cancer cells. Additionally, consumption of resistant starch was associated with reduced abdominal fat and improved insulin sensitivity. Increased serum glucagon-like peptide 1 (GLP-1) likely plays a role in promoting these health benefits. One rodent study that did not use isocaloric diets demonstrated that the use of resistant starch at 8% of the weight of the diet reduced body fat. This appears to be approximately equivalent to the human fiber requirement. In human subjects, insulin sensitivity is increased with the feeding of resistant starch. However, only 1 of several studies reports an increase in serum GLP-1 associated with resistant starch added to the diet. This means that other mechanisms, such as increased intestinal gluconeogenesis or increased adiponectin, may be involved in the promotion of improved insulin sensitivity. Future research may confirm that there will be improved health if human individuals consume the requirement for dietary fiber and a large amount of the fiber is fermentable.

The importance of GLP-1 and PYY in resistant starch's effect on body fat in mice.

Resistant starch (RS) is a dietary fermentable fiber that decreases body fat accumulation, and stimulates the secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) in rodents. GLP-1 and PYY are gut-secreted hormones with antiobesity effect. Thus, blocking the signals of increased GLP-1 and PYY may also block the effect of dietary RS on body fat. In a 10-week study, C57BL/6J and GLP-1 receptor null (GLP-1R KO) mice were fed control or 30% RS diet, and received daily intraperitoneal injection of either saline or PYY receptor antagonist (BIIE0246, 20 µg/kg body weight). Dietary RS significantly decreased body fat accumulation only in wild-type mice that has saline injection, but not in GLP-1R KO mice. PYY receptor antagonist diminished RS action on body fat in wild-type mice, but did not interfere with GLP-1R KO mice response to RS. Regardless of genotype and injection received, all RS-fed mice had increased cumulative food intake, cecal fermentation, and mRNA expression of proglucagon and PYY. Thus, our results suggest that increased GLP-1 and PYY is important in RS effects on body fat accumulation.

Prowashonupana barley dietary fibre reduces body fat and increases insulin sensitivity in Caenorhabditis elegans model.

Prowashonupana barley (PWB) is high in ß-glucan with moderate content of resistant starch. PWB reduced intestinal fat deposition (IFD) in wild type Caenorhabditis elegans (C. elegans, N2), and in sir-2.1 or daf-16 null mutants, and sustained a surrogate marker of lifespan, pharyngeal pumping rate (PPR), in N2, sir-2.1, daf-16, or daf-16/daf-2 mutants. Hyperglycaemia (2% glucose) reversed or reduced the PWB effect on IFD in N2 or daf-16/daf-2 mutants with a sustained PPR. mRNA expression of cpt-1, cpt-2, ckr-1, and gcy-8 were dose-dependently reduced in N2 or daf-16 mutants, elevated in daf-16/daf-2 mutants with reduction in cpt-1, and unchanged in sir-2.1 mutants. mRNA expressions were increased by hyperglycaemia in N2 or daf-16/daf-2 mutants, while reduced in sir-2.1 or daf-16 mutants. The effects of PWB in the C. elegans model appeared to be primarily mediated via sir-2.1, daf-16, and daf-16/daf-2. These data suggest that PWB and ß-glucans may benefit hyperglycaemia-impaired lipid metabolism.

Does Whole Grain Consumption Alter Gut Microbiota and Satiety?

This review summarizes recent studies examining whole grain consumption and its effect on gut microbiota and satiety in healthy humans. Studies comparing whole grains to their refined grain counterparts were considered, as were studies comparing different grain types. Possible mechanisms linking microbial metabolism and satiety are described. Clinical trials show that whole grain wheat, maize, and barley alter the human gut microbiota, but these findings are based on a few studies that do not include satiety components, so no functional claims between microbiota and satiety can be made. Ten satiety trials were evaluated and provide evidence that whole oats, barley, and rye can increase satiety, whereas the evidence for whole wheat and maize is not compelling. There are many gaps in the literature; no one clinical trial has examined the effects of whole grains on satiety and gut microbiota together. Once understanding the impact of whole grains on satiety and microbiota is more developed, then particular grains might be used for better appetite control. With this information at hand, healthcare professionals could make individual dietary recommendations that promote satiety and contribute to weight control.

High amylose resistant starch diet ameliorates oxidative stress, inflammation, and progression of chronic kidney disease.

Inflammation is a major mediator of CKD progression and is partly driven by altered gut microbiome and intestinal barrier disruption, events which are caused by: urea influx in the intestine resulting in dominance of urease-possessing bacteria; disruption of epithelial barrier by urea-derived ammonia leading to endotoxemia and bacterial translocation; and restriction of potassium-rich fruits and vegetables which are common sources of fermentable fiber. Restriction of these foods leads to depletion of bacteria that convert indigestible carbohydrates to short chain fatty acids which are important nutrients for colonocytes and regulatory T lymphocytes. We hypothesized that a high resistant starch diet attenuates CKD progression. Male Sprague Dawley rats were fed a chow containing 0.7% adenine for 2 weeks to induce CKD. Rats were then fed diets supplemented with amylopectin (low-fiber control) or high fermentable fiber (amylose maize resistant starch, HAM-RS2) for 3 weeks. CKD rats consuming low fiber diet exhibited reduced creatinine clearance, interstitial fibrosis, inflammation, tubular damage, activation of NFkB, upregulation of pro-inflammatory, pro-oxidant, and pro-fibrotic molecules; impaired Nrf2 activity, down-regulation of antioxidant enzymes, and disruption of colonic epithelial tight junction. The high resistant starch diet significantly attenuated these abnormalities. Thus high resistant starch diet retards CKD progression and attenuates oxidative stress and inflammation in rats. Future studies are needed to explore the impact of HAM-RS2 in CKD patients.