Gender‐based effect of absence of gut microbiota on the protective efficacy of Bifidobacterium longum‐fermented rice bran diet against inflammation‐associated colon tumorigenesis

Abstract

Dietary rice bran (RB) has shown capacity to influence metabolism by modulation of gut microbiota in individuals at risk for colorectal cancer (CRC), which warranted attention for delineating mechanisms for bidirectional influences and cross‐feeding between the host and RB‐modified gut microbiota to reduce CRC. Accordingly, in the present study, fermented rice bran (FRB, fermented with a RB responsive microbe Bifidobacterium longum), and non‐fermented RB were fed as 10% w/w (diet) to gut microbiota‐intactspf or germ‐free micegf to investigate comparative efficacy against inflammation‐associated azoxymethane/dextran sodium sulfate (AOM/DSS)‐induced CRC. Results indicated both microbiota‐dependent and independent mechanisms for RB meditated protective efficacy against CRC that was associated with reduced neoplastic lesion size and local‐mucosal/systemic inflammation, and restoration of colonic epithelial integrity. Enrichment of beneficial commensals (such as, Clostridiales, Blautia, Roseburia), phenolic metabolites (benzoate and catechol metabolism), and dietary components (ferulic acid‐4 sulfate, trigonelline, and salicylate) were correlated with anti‐CRC efficacy. Germ‐free studies revealed gender‐specific physiological variables could differentially impact CRC growth and progression. In the germ‐free females, the RB dietary treatment showed a ∼72% reduction in the incidence of colonic epithelial erosion when compared to the ∼40% reduction in FRB‐fed micegf. Ex vivo fermentation of RB did not parallel the localized‐protective benefits of gut microbial metabolism by RB in damaged colonic tissues. Findings from this study suggest potential needs for safety considerations of fermented fiber rich foods as dietary strategies against severe inflammation‐associated colon tumorigenesis (particularly with severe damage to the colonic epithelium).

Metagenomic meta-analysis of the gut microbiome in the different primary locations of colorectal cancer

“…Silva-Reis R et al found that Blautia was with high abundance when dimethylhydrazine induced colorectal carcinogenesis [57]. But Kumar R et al considered that the enrichment of Blautia was correlated with anti-CRC e cacy of dietary rice bran [74]. Increasing abundance level of Eubacterium also was associated with anti-CRC e cacy of berberine [75].…”

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

“…The methods of this study have been previously published [ 17 ]. Six-week-old male BALB/c mice ( n = 40) (Charles River Laboratories, Wilmington, MA, USA) were housed in an animal facility at The University of Colorado Denver-AMC, fed a control AIN-93M pellet diet, and acclimatized for 1 week.…”

“…Whole grain brown rice and rice bran contain unique bioactive phytochemicals, vitamins, and prebiotics that have exhibited the control and prevention of several types of human cancers [ 10 , 11 , 12 , 13 ], including colorectal cancer in both animals and humans [ 14 , 15 , 16 , 17 , 18 , 19 ]. Rice bran is the nutrient-rich outer layer of rice milled off to yield white rice.…”

“…Rice bran CRC protective phytochemicals induce apoptosis and block cell proliferation to prevent tumor growth [ 25 , 26 , 27 ]. Numerous studies have previously documented the CRC prevention properties associated with brown rice and rice bran [ 13 , 14 , 16 , 17 , 28 , 29 , 30 ]. The bioactive metabolites from rice bran reduce inflammation by scavenging free radicals [ 31 ] and triggering anti-tumor immune responses in the colonic microenvironment [ 32 , 33 , 34 ].…”

“…Though there are well-established studies in the literature documenting rice bran’s role in CRC control and prevention [ 13 , 14 , 16 , 17 , 28 , 29 , 30 ], a gap in knowledge exists for the time-dependent, weekly changes to fecal microbial communities and metabolites associated with the host digestion of rice bran, which are directly and indirectly contributing to reducing CRC formation. In this regard, we recently reported how rice bran intake results in less local and systemic inflammation in the colon tissue and plasma in an AOM-DSS pre-clinical murine model [ 17 ]. The rice bran-fed mouse group had enriched Clostridiales , Lachnospiraceae , and Ruminiclostridium in the cecum and colon.…”