Abstract 1265: Protective efficacy of gut microbiome and microbial metabolites after rice bran consumption against colon tumorigenesis

Colorectal cancer (CRC) is the 2nd leading cause of cancer-related deaths in US. Therefore, practical interventions that reduce incidence of adenomatous polyps and/or prevent their progression to CRC are urgently needed. In this regard, several studies have reported the chemopreventive potential of dietary rice bran [a wasted ‘by-product9 of white rice (Oryza sativa) processing] against CRC. Given that high heat can stabilize rice-bran for safe human consumption, our research efforts are evaluating ‘stabilized-rice bran9, as a functional food for CRC control and prevention. Rice bran has been previously shown to increase colonization of native gut probiotics and undergo microbiota fermentation. However, little is known about rice bran constituents as prebiotics, microbial substrates that promote healthy gut microbiota, and how these microbes produce novel, bioactive microbial metabolites. In this regard, our studies show that native gut probiotic - fermented rice bran extracts have strong in vitro activity against CRC cells and significantly decrease their colonosphere formation (a stem cell characteristic). Rice bran (fermented and non-fermented) also strongly inhibits TNF alpha-induced NF-kappa B activation and interleukin (IL)- 4-induced expression of CD44, which along with its variant form (CD44 v3-v6) plays an essential role in the adhesion and infiltration of inflammatory cells in CRC. Notably, even the stool extracts from rice bran-fed CRC survivors showed increased inhibitory effects on CRC cell viability compared to the stools collected from the same individuals prior to rice bran consumption. Next, extensive in vivo investigations were performed to determine the relative efficacy of dietary rice bran-modified gut microbiota and microbiota-fermented rice bran on inflammation associated-colon tumorigenesis. First, Bifidobacterium Longum -fermented (fermented with selected rice bran responsive microbe that was induced during rice bran feeding clinical trials) and non-fermented dietary rice bran were fed to conventionally-raised or germ-free mice and evaluated for their comparative efficacy against azoxymethane (AOM)/ dextran sodium sulphate (DSS)-induced CRC. In second set of studies, we ‘humanized9 gut of germ-free mice with stool inoculum from rice bran feeding human clinical trials and evaluated their efficacy against AOM/DSS-induced CRC. In conventional mice study, both the rice bran diets showed protective efficacy against CRC. Interestingly, germ-free mice having undergone transfaunation with rice-bran modified stool inoculum showed significantly less cancerous lesions compared to mice humanized with control stool inoculums, indicating that rice bran has the potential to re-structure the ‘high risk9 gut microflora of CRC patients towards the colonization of populations with protective effects against CRC growth and progression. Citation Format: Akhilendra K. Maurya, Sushil Kumar, Rama Kant, Dileep Kumar, Bupinder Raina, Anita Yadav, Elizabeth P. Ryan, Komal Raina. Protective efficacy of gut microbiome and microbial metabolites after rice bran consumption against colon tumorigenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1265.