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Heat-stabilised rice bran consumption by colorectal cancer survivors modulates stool metabolite profiles and metabolic networks: a randomised controlled trial.

ABSTRACT: Rice bran (RB) consumption has been shown to reduce colorectal cancer (CRC) growth in mice and modify the human stool microbiome. Changes in host and microbial metabolism induced by RB consumption was hypothesised to modulate the stool metabolite profile in favour of promoting gut health and inhibiting CRC growth. The objective was to integrate gut microbial metabolite profiles and identify metabolic pathway networks for CRC chemoprevention using non-targeted metabolomics. In all, nineteen CRC survivors participated in a parallel randomised controlled dietary intervention trial that included daily consumption of study-provided foods with heat-stabilised RB (30 g/d) or no additional ingredient (control). Stool samples were collected at baseline and 4 weeks and analysed using GC-MS and ultra-performance liquid chromatography-MS. Stool metabolomics revealed 93 significantly different metabolites in individuals consuming RB. A 264-fold increase in ?-hydroxyisovaleroylcarnitine and 18-fold increase in ?-hydroxyisovalerate exemplified changes in leucine, isoleucine and valine metabolism in the RB group. A total of thirty-nine stool metabolites were significantly different between RB and control groups, including increased hesperidin (28-fold) and narirutin (14-fold). Metabolic pathways impacted in the RB group over time included advanced glycation end products, steroids and bile acids. Fatty acid, leucine/valine and vitamin B6 metabolic pathways were increased in RB compared with control. There were 453 metabolites identified in the RB food metabolome, thirty-nine of which were identified in stool from RB consumers. RB consumption favourably modulated the stool metabolome of CRC survivors and these findings suggest the need for continued dietary CRC chemoprevention efforts.

SUBMITTER: Brown DG

PROVIDER: S-EPMC5654571 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Heat-stabilised rice bran consumption by colorectal cancer survivors modulates stool metabolite profiles and metabolic networks: a randomised controlled trial.

Brown Dustin G DG Borresen Erica C EC Brown Regina J RJ Ryan Elizabeth P EP

The British journal of nutrition 20170501 9

Rice bran (RB) consumption has been shown to reduce colorectal cancer (CRC) growth in mice and modify the human stool microbiome. Changes in host and microbial metabolism induced by RB consumption was hypothesised to modulate the stool metabolite profile in favour of promoting gut health and inhibiting CRC growth. The objective was to integrate gut microbial metabolite profiles and identify metabolic pathway networks for CRC chemoprevention using non-targeted metabolomics. In all, nineteen CRC s ...[more]

PMID: 28643618

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Project description: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.

Project description:BackgroundEnvironmental 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.ObjectiveThe 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.MethodsA 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.ResultsTwenty-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.ConclusionsRB 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.

Project description:Rice bran is a high-quality and renewable livestock feed material rich in nutrients and bioactive substances. To investigate the effects of dietary supplementation with fermented heat-treated rice bran on the performance, apparent digestibility of nutrients, cecal microbiota and metabolites in laying hens, a total of 128 18-week-old Hy-Line brown layers were randomly assigned to four treatment groups: 2.5% HRB (basal diet contained 2.5% heat-treated rice bran), 5.0% HRB (5.0% heat-treated rice bran), 2.5% FHRB (2.5% fermented heat-treated rice bran), 5.0% FHRB (5.0% fermented heat-treated rice bran). Results showed that FHRB supplementation significantly increased the average daily feed intake (ADFI) during 25-28 weeks, and improved apparent digestibility of dry matter (DM), crude protein (CP), ether extract (EE) and crude fiber (CF) in laying hens. Moreover, feeding 5.0% of HRB and FHRB resulted higher egg production (EP) and average egg weight (AEW) during the feeding period, and decreased the feed conversion ratio (FCR) during 21 to 28 weeks. The alpha and beta diversity indices indicated that FHRB altered the cecal microbiota. In particular, dietary supplementation with FHRB significantly increased the relative abundances of Lachnospira and Clostridium. Compared with the 2.5% level of supplementation, supplementing 5.0% HRB and 5.0% FHRB increased the relative abundances of Firmicutes, Ruminococcus and Peptococcus, and lowered the relative abundance of Actinobacteria. Furthermore, dietary FHRB supplementation significantly increased the concentration of short-chain fatty acids in cecum and changed the overall metabolome. The results of correlation analysis showed a close interaction between cecal microbiota, metabolites and apparent digestibility of nutrients. Taken together, we revealed that FHRB supplementation can induce characteristic structural and metabolic changes in the cecal microbiome, which could potentially promote nutrient digestion and absorption, and improve the production performance of laying hens.

Dataset Information

Heat-stabilised rice bran consumption by colorectal cancer survivors modulates stool metabolite profiles and metabolic networks: a randomised controlled trial.

Publications

Heat-stabilised rice bran consumption by colorectal cancer survivors modulates stool metabolite profiles and metabolic networks: a randomised controlled trial.

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