Gender-based effect of absence of gut microbiota on the protective efficacy of Bifidobacterium longum-fermented rice bran diet against inflammation-associated colon tumorigenesis.

Dietary rice bran (RB) has shown capacity to influence metabolism by modulation of gut microbiota in individuals at risk for colorectal cancer (CRC), which warranted attention for delineating mechanisms for bidirectional influences and cross-feeding between the host and RB-modified gut microbiota to reduce CRC. Accordingly, in the present study, fermented rice bran (FRB, fermented with a RB responsive microbe Bifidobacterium longum), and non-fermented RB were fed as 10% w/w (diet) to gut microbiota-intactspf or germ-free micegf to investigate comparative efficacy against inflammation-associated azoxymethane/dextran sodium sulfate (AOM/DSS)-induced CRC. Results indicated both microbiota-dependent and independent mechanisms for RB meditated protective efficacy against CRC that was associated with reduced neoplastic lesion size and local-mucosal/systemic inflammation, and restoration of colonic epithelial integrity. Enrichment of beneficial commensals (such as, Clostridiales, Blautia, Roseburia), phenolic metabolites (benzoate and catechol metabolism), and dietary components (ferulic acid-4 sulfate, trigonelline, and salicylate) were correlated with anti-CRC efficacy. Germ-free studies revealed gender-specific physiological variables could differentially impact CRC growth and progression. In the germ-free females, the RB dietary treatment showed a ∼72% reduction in the incidence of colonic epithelial erosion when compared to the ∼40% reduction in FRB-fed micegf . Ex vivo fermentation of RB did not parallel the localized-protective benefits of gut microbial metabolism by RB in damaged colonic tissues. Findings from this study suggest potential needs for safety considerations of fermented fiber rich foods as dietary strategies against severe inflammation-associated colon tumorigenesis (particularly with severe damage to the colonic epithelium).

Assessment of potentially toxic trace element contamination in urban allotment soils and their uptake by onions: A preliminary case study from Sheffield, England.

Toxic trace element (TTE) contamination in urban soils may pose potential health risks, especially in cities with previous industrial activities. This study aimed to investigate soil contamination in urban allotments in Sheffield, the uptake of TTEs in autumn and spring sown onions (Allium cepa), and their potential risks on human health via consumption of the crops. Paired soil and plant samples were taken in triplicates from four private allotments to assess potentially elevated levels of lead (Pb), zinc (Zn), copper (Cu), arsenic (As), and chromium (Cr). These elements in soils exceeded the ambient background levels for England. Both Pb and As exceeded some UK and EU soil tolerable limits. Concentration factors (CF) were calculated as the ratio of trace element in the plant as compared to that in the soil, and uptake rates were in the order Zn>Cu>Cr>Pb>As. Concentrations were higher for most TTEs in spring sown onions (SSO), and had significantly higher CF (p < 0.05) for Pb and Cr than autumn sown onions (ASO), whereas the opposite was true for As. Toxic elements in plants did not exceed FAO/WHO intake limits when considering TTE content per plant and consumption rates. Human health risk assessment calculations using target hazard quotients (THQ) and hazard indexes (HI) indicated that consuming onions alone did not pose an immediate health risk.

Metabolic pathway elucidation towards time- and dose-dependent electrophoretic screening of stable oxidative phenolic compounds.

This study demonstrates an untested link between model phenolic compounds and the formation/electrophoretic separation of stable urinary metabolites. Sterically encumbered carbonyl groups were examined, and mass determination was used to confirm the presence and stability of two oxidative metabolites of pentachlorophenol: tetrachloro-1,2-benzoquinone and tetrachloro-1,4-dihydroquinone. Subsequently, baseline resolved separation of pentachlorophenol and the two oxidative metabolites was demonstrated under the following conditions: 75 mM sodium tetraborate buffer (pH = 8.5) with 5 % methanol and 50 mM SDS, +10.0 kV running voltage, injection time = 5.0 s, effective capillary length = 55 cm, and run temperature = 20 °C. Results not only provide key metabolic inferences for pentachlorophenol, they also exhibit improvements in the ability to separate and detect changes in urinary metabolites in response to phenolic-related exposure.

Integrated Microbiota and Metabolite Changes following Rice Bran Intake during Murine Inflammatory Colitis-Associated Colon Cancer and in Colorectal Cancer Survivors.

Dietary rice bran-mediated inhibition of colon carcinogenesis was demonstrated previously for carcinogen-induced rodent models via multiple anti-cancer mechanisms. This study investigated the role of dietary rice bran-mediated changes to fecal microbiota and metabolites over the time course of colon carcinogenesis and compared murine fecal metabolites to human stool metabolic profiles following rice bran consumption by colorectal cancer survivors (NCT01929122). Forty adult male BALB/c mice were subjected to azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colitis-associated colon carcinogenesis and randomized to control AIN93M (n = 20) or diets containing 10% w/w heat-stabilized rice bran (n = 20). Feces were serially collected for 16S rRNA amplicon sequencing and non-targeted metabolomics. Fecal microbiota richness and diversity was increased in mice and humans with dietary rice bran treatment. Key drivers of differential bacterial abundances from rice bran intake in mice included Akkermansia, Lactococcus, Lachnospiraceae, and Eubacterium xylanophilum. Murine fecal metabolomics revealed 592 biochemical identities with notable changes to fatty acids, phenolics, and vitamins. Monoacylglycerols, dihydroferulate, 2-hydroxyhippurate (salicylurate), ferulic acid 4-sulfate, and vitamin B6 and E isomers significantly differed between rice bran- and control-fed mice. The kinetics of murine metabolic changes by the host and gut microbiome following rice bran consumption complemented changes observed in humans for apigenin, N-acetylhistamine, and ethylmalonate in feces. Increased enterolactone abundance is a novel diet-driven microbial metabolite fecal biomarker following rice bran consumption in mice and humans from this study. Dietary rice bran bioactivity via gut microbiome metabolism in mice and humans contributes to protection against colorectal cancer. The findings from this study provide compelling support for rice bran in clinical and public health guidelines for colorectal cancer prevention and control.

Multi-omics resources for targeted agronomic improvement of pigmented rice.

Pigmented rice (Oryza sativa L.) is a rich source of nutrients, but pigmented lines typically have long life cycles and limited productivity. Here we generated genome assemblies of 5 pigmented rice varieties and evaluated the genetic variation among 51 pigmented rice varieties by resequencing an additional 46 varieties. Phylogenetic analyses divided the pigmented varieties into four varietal groups: Geng-japonica, Xian-indica, circum-Aus and circum-Basmati. Metabolomics and ionomics profiling revealed that black rice varieties are rich in aromatic secondary metabolites. We established a regeneration and transformation system and used CRISPR-Cas9 to knock out three flowering time repressors (Hd2, Hd4 and Hd5) in the black Indonesian rice Cempo Ireng, resulting in an early maturing variety with shorter stature. Our study thus provides a multi-omics resource for understanding and improving Asian pigmented rice.

Solutions to Enhance Health with Alternative Treatments (SEHAT) protocol: a double-blinded randomised controlled trial for gut microbiota-targeted treatment of severe acute malnutrition using rice bran in ready-to-use therapeutic foods in Indonesia.

INTRODUCTION: Current formulations of ready-to-use therapeutic foods (RUTFs) to treat severe acute malnutrition (SAM) in children focus on nutrient density and quantity. Less attention is given to foods targeting gut microbiota metabolism and mucosal barrier functions. Heat-stabilised rice bran contains essential nutrients, prebiotics, vitamins and unique phytochemicals that have demonstrated favourable bioactivity to modulate gut microbiota composition and mucosal immunity. This study seeks to examine the impact of RUTF with rice bran on the microbiota during SAM treatment, recovery and post-treatment growth outcomes in Jember, Indonesia. Findings are expected to provide insights into rice bran as a novel food ingredient to improve SAM treatment outcomes. METHODS AND ANALYSIS: A total of 200 children aged 6-59 months with uncomplicated SAM (weight-for-height z-scores (WHZ) <-3, or mid-upper arm circumference (MUAC) <115 mm or having bilateral pitting oedema +/++) or approaching SAM (WHZ<-2.5) will be enrolled in a double-blinded, randomised controlled trial. Children in the active control arm will receive a locally produced RUTF; those in the intervention arm will receive the local RUTF with 5% rice bran. Children will receive daily RUTF treatment for 8 weeks and be monitored for 8 weeks of follow-up. Primary outcomes include the effectiveness of RUTF as measured by changes in weight, WHO growth z-scores, MUAC and morbidity. Secondary outcomes include modulation of the gut microbiome and dried blood spot metabolome, the percentage of children recovered at weeks 8 and 12, and malnutrition relapse at week 16. An intention-to-treat analysis will be conducted for each outcome. ETHICS AND DISSEMINATION: The findings of this trial will be submitted to peer-reviewed journals and will be presented at relevant conferences. Ethics approval obtained from the Medical and Health Research Ethical Committee at the Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Madain Yogyakarta Ref. No.: KE/FK/0546/EC/2022 and KE/FK/0703/EC/2023 and from Colorado State University IRB#1823, OHRP FWA00000647. TRIAL REGISTRATION NUMBER: NCT05319717.

Non-Targeted Dried Blood Spot-Based Metabolomics Analysis Showed Rice Bran Supplementation Effects Multiple Metabolic Pathways during Infant Weaning and Growth in Mali.

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.

Metabolomics of Rice Bran Differentially Impacted by Fermentation With Six Probiotics Demonstrates Key Nutrient Changes for Enhancing Gut Health.

The consumption of rice bran has been shown to have a positive effect on nutritional status and prevention of chronic diseases related to hundreds of metabolites with bioactivity. Consumption after fermentation can lead to specific beneficial effects, yet is lacking complete characterization when fermented with diverse strains. The objective of this study was to examine the effect of fermentation on the rice bran metabolite profile. Bacterial probiotics (Bifidobacterium longum, Limosilactobacillus fermentum, Lacticaseibacillus paracasei, Lacticaseibacillus rhamnosus and, Escherichia coli) were used to ferment rice bran alone or after incubation with yeast probiotic Saccharomyces boulardii. Fermented rice bran was methanol extracted and analyzed by UPLC-MS/MS. The metabolome of the two fermentation types was deeply modified when compared with non-fermented rice bran. The two-step fermentation provided alternative substrate to the bacteria in a few cases. Key metabolites of high nutritional value (essential amino acids, vitamins) and gut health (arabinose, maltotriose) were identified.

Arsenic speciation in rice bran: Agronomic practices, postharvest fermentation, and human health risk assessment across the lifespan.

Arsenic (As) exposure is a global public health concern affecting millions worldwide and stems from drinking water and foods containing As. Here, we assessed how agronomic practices and postharvest fermentation techniques influence As concentrations in rice bran, and calculated health risks from consumption. A global suite of 53 rice brans were tested for total As and speciation. Targeted quantification of inorganic As (iAs) concentrations in rice bran were used to calculate Target Hazard Quotient (THQ) and Lifetime Cancer Risk (LCR) across the lifespan. Mean iAs was highest in Thailand rice bran samples (0.619 mg kg-1) and lowest in Guatemala (0.017 mg kg-1) rice bran samples. When comparing monosodium-methanearsonate (MSMA) treated and the Native-soil counterpart under the irrigation technique Alternate Wetting and Drying (AWD) management, the MSMA treatment had significantly higher total As (p = 0.022), and iAs (p = 0.016). No significant differences in As concentrations were found between conventional and organic production, nor between fermented and non-fermented rice bran. Health risk assessment calculations for the highest iAs-rice bran dosage scenario for adults, children and infants exceeded THQ and LCR thresholds, and LCR was above threshold for median iAs-rice bran. This environmental exposure investigation into rice bran provides novel information with food safety guidance for an emerging global ingredient.

Daily Rice Bran Consumption for 6 Months Influences Serum Glucagon-Like Peptide 2 and Metabolite Profiles without Differences in Trace Elements and Heavy Metals in Weaning Nicaraguan Infants at 12 Months of Age.

BACKGROUND: Environmental enteric dysfunction (EED) is associated with chronic gut inflammation affecting nutrient absorption and development of children, primarily in low- and middle-income countries. Several studies have shown that rice bran (RB) supplementation provides nutrients and modulates gut inflammation, which may reduce risk for undernutrition. OBJECTIVE: The aim was to evaluate the effect of daily RB dietary supplementation for 6 mo on serum biomarkers in weaning infants and associated changes in serum and stool metabolites. METHODS: A 6-mo randomized-controlled dietary intervention was conducted in a cohort of weaning 6-mo-old infants in León, Nicaragua. Anthropometric indices were obtained at 6, 8, and 12 mo. Serum and stool ionomics and metabolomics were completed at the end of the 6-mo intervention using inductively coupled plasma MS and ultra-high performance LC-tandem MS. The ɑ1-acid glycoprotein, C-reactive protein, and glucagon-like peptide 2 (GLP-2) serum EED biomarkers were measured by ELISA. RESULTS: Twenty-four infants in the control group and 23 in the RB group successfully completed the 6-mo dietary intervention with 90% dietary compliance. RB participants had higher concentrations of GLP-2 as compared with control participants at 12 mo [median (IQR): 743.53 (380.54) pg/mL vs. 592.50 (223.59) pg/mL; P = 0.04]. Metabolite profiles showed significant fold differences of 39 serum metabolites and 44 stool metabolites from infants consuming RB compared with control, and with significant metabolic pathway enrichment scores of 4.7 for the tryptophan metabolic pathway, 5.7 for polyamine metabolism, and 5.7 for the fatty acid/acylcholine metabolic pathway in the RB group. No differences were detected in serum and stool trace elements or heavy metals following daily RB intake for 6 mo. CONCLUSIONS: RB consumption influences a suite of metabolites associated with growth promotion and development, while also supporting nutrient absorption as measured by changes in serum GLP-2 in Nicaraguan infants. This clinical trial was registered at https://clinicaltrials.gov as NCT02615886.