Dietary supplementation with rice bran or navy bean alters gut bacterial metabolism in colorectal cancer survivors.

SCOPE: Heat-stabilized rice bran (SRB) and cooked navy bean powder (NBP) contain a variety of phytochemicals that are fermented by colonic microbiota and may influence intestinal health. Dietary interventions with these foods should be explored for modulating colorectal cancer risk. METHODS AND RESULTS: A randomized-controlled pilot clinical trial investigated the effects of eating SRB (30 g/day) or cooked navy bean powder (35 g/day) on gut microbiota and metabolites (NCT01929122). Twenty-nine overweight/obese volunteers with a prior history of colorectal cancer consumed a study-provided meal and snack daily for 28 days. Volunteers receiving SRB or NBP showed increased gut bacterial diversity and altered gut microbial composition at 28 days compared to baseline. Supplementation with SRB or NBP increased total dietary fiber intake similarly, yet only rice bran intake led to a decreased Firmicutes:Bacteroidetes ratio and increased SCFA (propionate and acetate) in stool after 14 days but not at 28 days. CONCLUSION: These findings support modulation of gut microbiota and fermentation byproducts by SRB and suggest that foods with similar ability to increase dietary fiber intake may not have equal effects on gut microbiota and microbial metabolism.

Imaging Inflammatory Hypoxia in the Murine Gut.

The inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis, result in chronic inflammation to the gastrointestinal tract. In ulcerative colitis, inflammation tends to be more superficial and restricted to the colon; contrastingly, Crohn's disease presents as patchy, more penetrative inflammation that can occur throughout the gastrointestinal tract. Other differences between these diseases include the nature of their respective immune responses-Crohn's disease presents as a Th1 and ulcerative colitis as a Th2-type inflammation. During any inflammatory episode, metabolic demand on the tissue increases accompanying the influx of inflammatory cells, increasing the demand for ATP and oxygen. When availability of oxygen is limiting, tissues become hypoxic, which results in adaptive pathways to enable survival of hypoxic episodes. The primary pathway activated is the HIF (hypoxia inducible factor) transcription factor, which regulates adaptive pathways including genes controlling glycolytic metabolism and angiogenesis. In adequately oxygenated tissues (i.e. normoxia), the HIF protein is constantly produced, but oxygen-dependent enzymes called prolyl-hydroxylases utilize available oxygen to hydroxylate HIF on proline residues, targeting it for ubiquitination and subsequent degradation. Here we describe methods for inducing, visualizing, and quantifying in vivo "inflammatory hypoxia," using the murine gut as a model system.

Interaction of caffeine with the SOS response pathway in Escherichia coli.

BACKGROUND: Previous studies have highlighted the antimicrobial activity of caffeine, both individually and in combination with other compounds. A proposed mechanism for caffeine's antimicrobial effects is inhibition of bacterial DNA repair pathways. The current study examines the influence of sub-lethal caffeine levels on the growth and morphology of SOS response pathway mutants of Escherichia coli. METHODS: Growth inhibition after treatment with caffeine and methyl methane sulfonate (MMS), a mutagenic agent, was determined for E. coli mutants lacking key genes in the SOS response pathway. The persistence of caffeine's effects was explored by examining growth and morphology of caffeine and MMS-treated bacterial isolates in the absence of selective pressure. RESULTS: Caffeine significantly reduced growth of E. coli recA- and uvrA-mutants treated with MMS. However, there was no significant difference in growth between umuC-isolates treated with MMS alone and MMS in combination with caffeine after 48 h of incubation. When recA-isolates from each treatment group were grown in untreated medium, bacterial isolates that had been exposed to MMS or MMS with caffeine showed increased growth relative to controls and caffeine-treated isolates. Morphologically, recA-isolates that had been treated with caffeine and both caffeine and MMS together had begun to display filamentous growth. CONCLUSIONS: Caffeine treatment further reduced growth of recA- and uvrA-mutants treated with MMS, despite a non-functional SOS response pathway. However, addition of caffeine had very little effect on MMS inhibition of umuC-mutants. Thus, growth inhibition of E. coli with caffeine treatment may be driven by caffeine interaction with UmuC, but also appears to induce damage by additional mechanisms as evidenced by the additive effects of caffeine in recA- and uvrA-mutants.

Cancer-promoting effects of microbial dysbiosis.

Humans depend on our commensal bacteria for nutritive, immune-modulating, and metabolic contributions to maintenance of health. However, this commensal community exists in careful balance that, if disrupted, enters dysbiosis; this has been shown to contribute to the pathogenesis of colon, gastric, esophageal, pancreatic, laryngeal, breast, and gallbladder carcinomas. This development is closely tied to host inflammation, which causes and is aggravated by microbial dysbiosis and increases vulnerability to pathogens. Advances in sequencing technology have increased our ability to catalog microbial species associated with various cancer types across the body. However, defining microbial biomarkers as cancer predictors presents multiple challenges, and existing studies identifying cancer-associated bacteria have reported inconsistent outcomes. Combining metabolites and microbiome analyses can help elucidate interactions between gut microbiota, metabolism, and the host. Ultimately, understanding how gut dysbiosis impacts host response and inflammation will be critical to creating an accurate picture of the role of the microbiome in cancer.