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 β-hydroxyisovaleroylcarnitine and 18-fold increase in β-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.
Highlights
Convincing evidence supports that foods rich in phytochemicals and dietary fibre decrease risk of colorectal cancer (CRC)(1,2,3)
Of the ninety-three stool metabolites changed with rice bran (RB) consumption, thirty-three metabolites increased and sixty metabolites decreased after 4 weeks (Fig. 1(a) and (b)). β-Hydroxyisovaleroylcarnitine and hydroxybutyrlcarnitine showed a 265-fold and 66-fold increase over time, respectively
The primary objective of this study was to understand the stool metabolite profile differences between CRC survivors consuming a diet supplemented with RB for 4 weeks compared with a control group
Summary
Convincing evidence supports that foods rich in phytochemicals and dietary fibre decrease risk of colorectal cancer (CRC)(1,2,3). Whole grains are a rich source of dietary fibre and phytochemicals that have been studied for cancer chemopreventive properties[5,6]. Clinical trials established the feasibility of increased consumption of heat-stabilised RB in people and showed that RB intake can modulate the human stool microbiome[15,21,22]. These studies helped determine what phytochemicals from RB interact for enhanced microbial metabolism in the colon and excretion in stool. We hypothesised that stool metabolites resulting from both host and microbial metabolism following dietary RB intake represent viable, chemopreventive agents for inhibition of colonic inflammation and CRC recurrence. Results from this study have important dietary implications for prevention of primary and secondary CRC recurrence in adults
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