pubmed.ncbi.nlm.nih.gov

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

Randomized Controlled Trial

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

Dustin G Brown et al. Br J Nutr. 2017 May.

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.

Keywords: AGE advanced glycation end product; CRC colorectal cancer; RB Rice bran; UPLC ultra-performance liquid chromatography; Colorectal cancer; Metabolic pathways; Metabolomics; Phytochemicals; Rice bran.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1

Stool metabolite profile differences in the rice bran group over time. (a) Stool metabolites that were significantly different between 4-week and baseline time points with fold change values ≥5·00 and (b) stool metabolites that were significantly different between 4-week and baseline time points and had fold change values <5·00., Metabolites with significance and were identified in the rice bran food metabolome (see online Supplementary Table S3).

Fig. 2
Fig. 2

Pathway set enrichment scores for stool metabolome. (a) Metabolic pathways in rice bran over time that were significantly different between 4-week and baseline time points and (b) rice bran diet compared with control diet at 4 weeks. Pathway set enrichment scores were determined as defined in the ‘Methods’ section, and are presented for pathways with scores ≥2. SAM, S-adenosyl methionine.

Fig. 3
Fig. 3

Stool metabolomic pathway network analysis of lipid, cofactor and vitamin metabolites significantly different in rice bran consumers at 4 weeks compared with baseline. Pathway specific network views (Cytoscape) are presented for (a) steroid metabolism, (b) primary bile acid metabolism, (c) inositol metabolism, (d) cofactors and vitamin metabolism. Each metabolite is represented as a node, extending from a central metabolic pathway (with pathway impact score). A pathway set enrichment score ≥2 implies that pathway contains more metabolites of statistical significance relative to the entire study. The size of a node is proportional to the fold change between baseline and 4-week time points. A node coloured red represents metabolites with significantly (P ≤0·05) higher expression at 4 weeks compared with baseline. A node coloured dark green represents metabolites with significantly lower expression at 4 weeks compared with baseline. Nodes coloured pink or light green represent metabolites trending towards significance (0·05 < P ≤0·1) with higher expression at 4 weeks and lower expression at 4 weeks, respectively. CEHC, carboxyethyl-hydroxychroman.

Fig. 4
Fig. 4

Stool metabolomic pathway network analysis of carbohydrate and amino acid metabolites significantly different in rice bran consumers at 4 weeks compared with baseline. Pathway specific network views (Cytoscape) are presented for (a) advanced glycation end product metabolism, (b) leucine, isoleucine and valine metabolism, (c) methionine, cysteine, S-adenosyl methionine (SAM) and taurine metabolism, (d) urea cycle; arginine and proline metabolism. Each metabolite is represented as a node, extending from a central metabolic pathway (with pathway impact score). A pathway set enrichment score ≥2 implies that pathway contains more metabolites of statistical significance relative to the entire study. The size of a node is proportional to the fold change between baseline and 4-week time points. A node coloured red represents metabolites with significantly (P ≤0·05) higher expression at 4 weeks compared with baseline. A node coloured dark green represents metabolites with significantly lower expression at 4 weeks compared with baseline. Nodes coloured pink or light green represent metabolites trending towards significance (0·05 < P ≤0·1) with higher expression at 4 weeks and lower expression at 4 weeks, respectively.

Similar articles

Cited by

References

    1. Perera PST, Thompson RL, Wiseman MJ. Recent evidence for colorectal cancer prevention through healthy food, nutrition, and physical activity: implications for recommendations. Curr Nutr Rep. 2012;1:44–54.
    1. Li YH, Niu YB, Sun Y, et al. Role of phytochemicals in colorectal cancer prevention. World J Gastroenterol. 2015;21:9262–9272. - PMC - PubMed
    1. Liu RH. Potential synergy of phytochemicals in cancer prevention: mechanism of action. J Nutr. 2004;134:3479S–3485S. - PubMed
    1. Ferlay J, Soerjomataram I, Ervik M, et al. GLOBOCAN 2012 v1.1, Cancer Incidence and Mortality Worldwide, IARC CancerBase no. 11. Lyon: International Agency for Research on Cancer; 2014. [accessed February 2017]. http://globocan.iarc.fr.
    1. Slavin J. Whole grains and human health. Nutr Res Rev. 2004;17:99–110. - PubMed

Publication types

MeSH terms