No abstract

Rice bran contains essential nutrients, antioxidants, and bioactives with anti-inflammatory and diarrheal protective properties important for infants. This 6-month randomized controlled trial investigated the effects of heat-stabilized rice bran supplementation during Malian infant weaning. Fifty healthy 6-month-old infants were randomized to a rice bran intervention (N = 25) or non-intervention control group (N = 25). Intervention infants received dose-escalating rice bran supplementation for 6 months (1–5 g/day). Monthly infant dried blood spot and anthropometric measurements were collected. Dried blood spot metabolite abundances were compared monthly according to diet for six months. Supplementation resulted in favorable weight-for-age and weight-for-length z-score changes. Non-targeted dried blood spot-based metabolomics identified 796 metabolites, of which 33% had significant fold differences between groups (7–12 months). Lipids and amino acids represented 70.6% of the metabolites identified. Rice bran supplementation during infant weaning significantly modulated the metabolites involved in antioxidant defenses and with neuroactive properties including reduced glutathione, glycine, glutamate, cysteinylglycine, tryptophan betaine, and choline. These findings support rice bran as a weaning ingredient to meet infant nutritional requirements and with the potential to reduce oxidative stress and improve cognitive outcomes. This study provides evidence for dried blood spots as a cost-effective tool to detect infant biomarkers of nutritional and metabolic status.

Rat kidney contains 3.5-kb and 2.8-kb mRNAs that encode for glutamate dehydrogenase (GDH). The levels of both mRNAs are increased gradually after onset of chronic metabolic acidosis and reach a maximum induction of 2.5-fold after 7 days. In contrast, during recovery from chronic acidosis, the levels of the GDH mRNAs are returned to normal within 1 day. The development of an acute metabolic acidosis causes a more rapid induction of GDH mRNA. This increase occurs after a 7-h lag and plateaus after 18 h at a level that is threefold greater than normal. A very similar profile was observed after the transfer of LLC-PK-F+ cells from normal medium to an acidic medium containing 10 mM bicarbonate and adjusted to pH 6.9. However, the transfer of cells from acidic to normal medium caused an immediate and rapid [half-life (t) = 1 h] decrease in GDH mRNA. The apparent half-lives of GDH mRNA were measured by treating cells grown in normal (t = 4 h) and acidic media (t = 12 h) with actinomycin D. Thus, increased stability may account for the induction of GDH mRNA that occurs during growth in response to acidosis. The levels of GDH mRNA are independently affected by changes in medium pH or bicarbonate concentration. The levels of GDH mRNA are also increased by treating cells with adenosine 3',5'-cyclic monophosphate, epinephrine, triiodothyronine, or retinoic acid, whereas treatment with angiotensin II, vasopressin, phorbol 12-myristate 13-acetate, or cycloheximide did not produce an increase. The inductive effect of dexamethasone, which is observed in vivo, is not reproduced in the LLC-PK-F+ cells.

Purpose: Examine the feasibility and preliminary effects of a lifestyle intervention of rice bran plus navy bean supplementation, and physical activity (PA) education on intake of fiber and whole grains, and PA levels. Design: Randomized-controlled, single-blinded. Setting: Academic institution and free-living. Subjects: Adults >18 years, with ≥1 adenomatous polyp removed within 3 years. Intervention: Participants received powder and pre-prepared meals and snacks that contained either rice bran (30 g/day) plus navy bean (30 g/day), or Fibersol-2® (10 g/day), for 12-weeks. All participants received a 1-hour (PA) education session. Measures: Feasibility was assessed by recruitment and retention rates, and compliance to the study foods and procedures. Three-day food logs were analyzed using Nutritionist Pro™ to estimate fiber intake, and the Automated Self-Administered 24-hour (ASA24®) Dietary Assessment Tool calculated Healthy Eating Index (HEI) whole grain and total scores. PA was measured using an ActivPAL™ accelerometer. Analysis: Continuous data were summarized as median, range, and percent change from baseline to post-intervention. Results: N = 20 (86.9%) completed the intervention. Compliance was 92% in the rice bran plus navy bean versus 89% in Fibersol-2®. Navy bean consumption increased from 2 g/day to 30 g/day, and rice bran from 0 g/day to 30 g/day. Fiber intake (g/day) increased by 73% versus 82%, HEI whole grain improved by 270% versus 37%, and HEI total improved by 10% versus 9.1% in rice bran plus navy bean and Fibersol-2®, respectively. Total PA (MET-hours/day) showed minimal change for intervention (+0.04%) and control (+4%). Conclusion: Findings merit a larger trial of rice bran plus navy bean and PA to evaluate efficacy for dietary and cancer prevention-related outcomes.

Background: Adenomatous polyps are associated with an increased risk of developing colorectal cancer. Physical activity (PA) and spending less time sedentary may reduce risk of polyp recurrence and cancer incidence. This study examined associations between PA, sedentary time, and stool metabolites in adults at high risk for developing colorectal cancer. Methods: Participants were ≥18 years old with ≥1 adenomatous polyps removed in the previous 3 years. PA and sedentary time were assessed using an activPAL™ accelerometer. Stool samples were analyzed for short-chain fatty acids, and primary/secondary bile acid metabolites by mass spectrometry. Linear regression models examined associations between PA, sedentary time, and stool parameters, with dietary fiber as a covariate. Results: Participants (N = 21) were 59 (9) years old and had a body mass index of 28.1 (3.35 kg/m2). Light-intensity PA was associated with butyrate (β = 1.88; 95% confidence interval [CI], 0.477 to 3.291) and propionate (β = 1.79; 95% CI, 0.862 to 2.724). Moderate to vigorous PA was associated with deoxycholic acid (β = −6.13; 95% CI, −12.14 to −0.11) and ursodeoxycholic acid (β = −0.45; 95% CI, −0.80 to −0.12) abundance. Conclusions: Both light and moderate to vigorous PA were associated with gut microbial metabolite production. These findings suggest the importance of examining PA intensity alongside stool metabolites for colorectal cancer prevention.

IntroductionDietary intake of whole grains and legumes and adequate physical activity (PA) have been associated with reduced colorectal cancer (CRC) risk. A single-blinded, two-arm, randomized, placebo-controlled pilot trial was implemented to evaluate the impact of a 12-week dietary intervention of rice bran + navy bean supplementation and PA education on metabolite profiles and the gut microbiome among individuals at high risk of CRC.MethodsAdults (n=20) were randomized 1:1 to dietary intervention or control. All participants received PA education at baseline. Sixteen study foods were prepared with either heat-stabilized rice bran + navy bean powder or Fibersol®-2 as a placebo. Intervention participants consumed 30 g rice bran + 30 g navy bean powder daily; those in the control group consumed 10 g placebo daily. Non-targeted metabolite profiling was performed by UPLC-MS/MS to evaluate plasma, urine, and stool at 0, 6, and 12 weeks. Stool was also analyzed for primary and secondary bile acids (BAs) and short chain fatty acids (SCFAs) by UPLC-MS/MS and microbial community structure via 16S amplicon sequencing. Two-way ANOVA was used to compare differences between groups for metabolites, and mixed models were used to compare differences between groups for BAs, SCFAs, and alpha and beta diversity measures of microbial community structure.ResultsAcross biological matrices, the intervention resulted in changes to several amino acid and lipid metabolites, compared to control. There was a 2.33-fold difference in plasma (p<0.001) and a 3.33-fold difference in urine (p=0.008) for the amino acid S-methylcysteine at 12 weeks. Fold-differences to 4-methoxyphenol sulfate in plasma and urine after 6 and 12 weeks (p<0.001) was a novel result from this combined rice bran and navy bean intervention in people. A 2.98-fold difference in plasma (p=0.002) and a 17.74-fold difference in stool (p=0.026) was observed for the lipid octadecenedioylcarnitine at 12 weeks. For stool BAs, 3-oxocholic acid was increased at 12 weeks compared to control within a subset of individuals (mean difference 16.2 ug/uL, p=0.022). No significant differences were observed between groups for stool SCFAs or microbial community structure.DiscussionDietary intake of rice bran + navy beans demonstrates beneficial modulation of host and gut microbial metabolism and represents a practical and affordable means of increasing adherence to national guidelines for CRC control and prevention in a high-risk population.

Objectives Self-reporting methods for dietary exposure are error-prone and have had limited impact to identify food components that mitigate disease risk. The purpose of this study was to use non-targeted and targeted metabolomics from feeding trials with rice bran and navy beans for the identification of dietary biomarkers across the lifespan. Methods Prepared meals/snacks, and biological samples from randomized-controlled trials performed in 50 infants, 38 children and 49 adults were utilized in this study. Diet groups were placebo control, rice bran, cooked navy bean powder, or a combination of rice bran/navy beans with increasing daily doses by age group and for duration of 4, 12 or 24 weeks per protocol. Plasma/dried blood spots, urine or stool samples were collected at a baseline, midpoint and endpoint. Non-targeted profiling was performed with UPLC-MS/MS, and metabolite quantification by LC-triple-quadropole (LC-QQQ-MS). A linear mixed model to compare between time points in each group was performed using SAS. Results The plasma/blood metabolomes contained between 771–1001 metabolites and showed variation in ∼20–30% of the profile following intervention. Fold changes over time and fold-differences in metabolite abundance were assessed by age (P < 0.05). There were 10–20 candidate identified from metabolomics across studies and with relevance to rice bran and/or navy bean were applied for targeted assay development. Food metabolomes confirmed metabolite origins and the host and microbial metabolism. Candidate metabolites included pipecolate, S-methlycysteine, S-methylcysteine sulfoxide, trigonelline, N-methyl-pipecolate, pyridoxal, 2-hydroxyhippurate, apigenin, xanthurenate, chiro-inositol, and salicylate. Inter-individual variation was reported across studies, ages and dietary patterns. Conclusions Dietary biomarkers for rice bran and/or navy bean intake merit additional selection criteria from non-targeted metabolomics. Targeted assays will need validation in larger cohort investigations using cross-over study designs and diverse dietary patterns. Funding Sources This work was supported by a grant from the National Institute of Foods and Agriculture-U.S Department of Agriculture (NIFA-USDA).

Hydrocephalus is a clinical manifestation of cerebrospinal fluid (CSF) accumulation, leading to ventriculomegaly and increased intracranial pressure. Diuretics and other pharmacotherapies have failed to treat hydrocephalus in the human population; therefore, treatment options remain exclusively surgical. The need to develop pharmacotherapies for the treatment of hydrocephalus remains an unmet clinical need and paramount to this need is the study of brain fluid regulation. Previous studies in our laboratory identified the transient receptor potential vanilloid 4 (TRPV4) channel as a potential regulatory hub protein in the choroid plexus responsible, in part, for the regulation of CSF production. Antagonists of the TRPV4 channel were shown to ameliorate hydrocephalus in a genetic rat model. The current studies highlight a novel drug target: serum‐ and glucocorticoid‐induced kinase 1 (SGK1) in the choroid plexus. A specific small molecular weight, membrane permeant inhibitor of SGK1, SI113, has shown promising results in cancer and metabolic research in recent years. In other tissues, SGK1 has been shown to phosphorylate and activate TRPV4 at the membrane, indicating SGK1 as an important upstream regulatory kinase. SI113 blocked TRPV4‐mediated transepithelial ion flux and barrier conductance increases in a cell culture model of human choroid plexus epithelia (HIBCPP line), and ameliorated ventriculomegaly in the genetic rat model. In hydrocephalic animals, there is an increased apical membrane signal in the choroid plexus epithelial cells via immunofluorescent localization of p‐SGK1 and TRPV4, but not of pan‐SGK1. This is not accompanied by a significant increase in either protein or transcript abundance as measured by western blotting or qPCR, respectively. The change in localization is, however, attenuated by treatment with SI113. Animals treated with SI113 show no change in amounts of TRPV4 or total SGK1, but do show significantly reduced levels of p‐SGK1. Thus, phosphorylation of SGK1 appears to be crucial for the activation of TRPV4 which is, in turn, a channel protein that is activated during the development of hydrocephalus. Like Trpv4‐/‐mice, Sgk1‐/‐mice do not show overt phenotypes, indicating pharmacological antagonism of the kinase would have minimal off‐target effects. Overall, these data provide a strong preclinical basis for the use of SGK1 inhibitors in the treatment of hydrocephalus.