Principal Investigator

Elizabeth P
Awardee Organization

Colorado State University
United States

Fiscal Year
Activity Code
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date

Rice Bran Microbial Metabolism for Colon Chemoprevention

Colorectal cancer (CRC) develops as a result of complex interactions between the host mucosal immune response, microbiota, diet components, colon cancer stem cells (CSC) and inflammatory mediators. Rice bran is a `wasted' agricultural byproduct of rice processing that has shown CRC chemopreventive efficacy in numerous animal studies. Our metabolomics investigations revealed novel probiotic metabolism of rice bran using an R03 award, and our completed human studies from a recent R21 award provide compelling support that rice bran is a promising, novel dietary agent to be metabolized by the gut microbiota in favor of reducing CRC. Rice bran is a unique source of plant lipids and contains distinct contents from wheat, oat and other cereal grains. Rice bran is distinguished by gamma oryzanol, a distinct ratio of tocotrienols and tocopherol isoforms, and essential nutrients. Notably, rice bran phenolics, phytic acid, and tricin possess CRC chemoprevention activity. Little, however, is known regarding the microbial byproducts of rice bran that our preliminary studies show may be increasing gut mucosal immunity, decreasing colonic inflammation, and reducing neoplastic growth. The major objective of this proposal is to fill a significant gap in our knowledge regarding the microbiome-mediated mechanisms of action for rice bran associated CRC chemopreventive efficacy. Pre-clinical mice studies and stool results from our pilot human clinical rice bran trial showed that dietary rice bran increases healthy native gut microflora and production of stool metabolites with anti-inflammatory activities, favoring reduced colon tumorigenesis. Human stool extracts collected post- rice bran consumption also showed stronger inhibitory effects on CRC cell viability compared to pre-rice bran consumption samples. These data provide compelling rationale for studying the role of these human microbial populations and the utilization of rice bran by these microbes for CRC growth inhibition. The feasibility of carcinogen-treated humanized mice is now established for CRC, and this approach merits testing of stool samples from CRC survivors before and after daily rice bran consumption. We hypothesize that the phytochemicals in rice bran serve as gut microbial substrates and are metabolized into bioactive microbial metabolites that impact the colonic microenvironment for enhanced efficacy against CRC. Our specific aims are: I) To study the influence of dietary rice bran on the human gut microbiota and the gut microbial metabolism of rice bran for effective CRC chemoprevention.; II) To examine and establish the role of dietary rice bran - human gut microbiota interactions on inflammatory/immune milieu and cancer stem cells in the colonic tumor microenvironment; and III) To identify and define the microbial metabolites of rice bran, and relate their specific metabolic/ molecular signatures with anti-CRC efficacy. The results from these studies will provide rice bran-mediated mechanisms associated with anti-CRC efficacy and promote inclusion of rice bran as a sustainable, global functional food for colon cancer chemoprevention.


  • Zarei I, Oppel RC, Borresen EC, Brown RJ, Ryan EP. Modulation of plasma and urine metabolome in colorectal cancer survivors consuming rice bran. Integrative food, nutrition and metabolism. 2019 May;6. (3). Epub 2019 Apr 5. PMID: 31396400
  • Parker KD, Maurya AK, Ibrahim H, Rao S, Hove PR, Kumar D, Kant R, Raina B, Agarwal R, Kuhn KA, Raina K, Ryan EP. Dietary Rice Bran-Modified Human Gut Microbial Consortia Confers Protection against Colon Carcinogenesis Following Fecal Transfaunation. Biomedicines. 2021 Feb 3;9. (2). PMID: 33546192
  • Brown DG, Borresen EC, Brown RJ, Ryan EP. Heat-stabilised rice bran consumption by colorectal cancer survivors modulates stool metabolite profiles and metabolic networks: a randomised controlled trial. The British journal of nutrition. 2017 May;117(9):1244-1256. PMID: 28643618
  • Hove PR, Nealon NJ, Chan SHJ, Boyer SM, Haberecht HB, Ryan EP. Integrated Profiling of Gram-Positive and Gram-Negative Probiotic Genomes, Proteomes and Metabolomes Revealed Small Molecules with Differential Growth Inhibition of Antimicrobial-Resistant Pathogens. Journal of dietary supplements. 2022 Sep 13: 1-23. Epub 2022 Sep 13. PMID: 36099186
  • Zarei I, Baxter BA, Oppel RC, Borresen EC, Brown RJ, Ryan EP. Plasma and Urine Metabolite Profiles Impacted by Increased Dietary Navy Bean Intake in Colorectal Cancer Survivors: A Randomized-Controlled Trial. Cancer prevention research (Philadelphia, Pa.). 2021 Apr;14(4):497-508. Epub 2020 Dec 24. PMID: 33361317
  • Kumar R, Maurya AK, Parker KD, Kant R, Ibrahim H, Kabir MI, Kumar D, Weber AM, Agarwal R, Kuhn KA, Ryan EP, Raina K. Gender-based effect of absence of gut microbiota on the protective efficacy of Bifidobacterium longum-fermented rice bran diet against inflammation-associated colon tumorigenesis. Molecular carcinogenesis. 2022 Oct;61(10):941-957. Epub 2022 Jul 20. PMID: 35856887
  • Nealon NJ, Parker KD, Lahaie P, Ibrahim H, Maurya AK, Raina K, Ryan EP. Bifidobacterium longum-fermented rice bran and rice bran supplementation affects the gut microbiome and metabolome. Beneficial microbes. 2019 Dec 9;10(8):823-839. Epub 2019 Sep 29. PMID: 31965839
  • Weber AM, Ibrahim H, Baxter BA, Kumar R, Maurya AK, Kumar D, Agarwal R, Raina K, Ryan EP. Integrated Microbiota and Metabolite Changes following Rice Bran Intake during Murine Inflammatory Colitis-Associated Colon Cancer and in Colorectal Cancer Survivors. Cancers. 2023 Apr 10;15. (8). PMID: 37190160