Integrated Microbiota and Metabolite Changes following Rice Bran Intake during Murine Inflammatory Colitis-Associated Colon Cancer and in Colorectal Cancer Survivors

Abstract

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.

Antitumor Effect and Gut Microbiota Modulation by Quercetin, Luteolin, and Xanthohumol in a Rat Model for Colorectal Cancer Prevention

“…The genus Eubacterium xylanophilum group was reduced in all flavonoid-treated cohorts, especially in the luteolin cohort ( Table 4 and Figure 7 ). Controversially, this genus was found to be increased in a CRC-mice cohort fed with rice bran, which improved the CRC condition [ 75 ]. Regarding the Oscillospiraceae and Ruminococcaceae families, a notable increase in the abundance of an uncultured genus within each family was found, which was particularly evident in the luteolin cohort ( Table 4 and Figure 7 ).…”

Exploring the Impact of Fermentation on Brown Rice: Health Benefits and Value-Added Foods—A Comprehensive Meta-Analysis

“…Moreover, it showed prophylactic properties against tumor development induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a crucial agent in lung cancer, the leading cause of cancer deaths in 2020 [26]. This fermented rice has also been associated with the inhibition of tumor formation in the colon [27], liver [28], and esophagus [29].…”