Dietary Rice Bran Phytochemicals and Microbial Metabolites for Colon Chemoprevent

用于结肠化学预防的膳食米糠植物化学物质和微生物代谢物

• 批准号: 8304033
• 负责人: Elizabeth P Ryan
• 金额: $ 19.04万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8304033
• 关键词: Agriculture; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Antioxidants; Attention; Bacteria; Bacteroides; Cancer Control; Cancer Model; Cancer Survivor; Carcinogens; Cell Death; Chemicals; Chemoprevention; Chemopreventive Agent; Clinical Trials; Colitis; Collection; Colon; Colon Carcinoma; Colonic Neoplasms; Colorectal Cancer; Consumption; DNA Sequence; Data; Data Analyses; Development; Diet; Dietary Intervention; Eating; Epithelial; Escherichia coli; Exhibits; Fatty Acids; Feces; Fermentation; Food; Goals; Health; Homeostasis; Human; Individual; Inflammation; Inflammation Mediators; Inositol; Intake; Intervention; Intestines; Investigation; Knowledge; Laboratories; Lactic acid; Lactobacillus; Lead; Lipids; Macronutrients Nutrition; Malignant Neoplasms; Measures; Mediating; Metabolic; Metabolic Biotransformation; Metabolism; Microbe; Micronutrients; Modeling; Mus; Neptune; Nutritional; Outcome Study; Participant; Phytochemical; Phytosterols; Placebo Control; Plants; Population; Preventive; Prevotella; Probiotics; Production; Public Health; Randomized; Reporting; Research; Research Project Grants; Rice; Risk; Ruminococcus; Sampling; Structure; Techniques; Testing; Tissues; Tocopherols; Tocotrienols; Volatile Fatty Acids; Work; base; bran (dietary); cancer cell; cancer prevention; cancer recurrence; cancer risk; colorectal cancer prevention; esterase; ferulic acid; gamma-oryzanol; innovation; metabolomics; microbial; microbial community; microbiome; microorganism; mortality; multidisciplinary; novel; phenolic acid; phytate; prevent; tool; tumorigenesis; two-arm study

DESCRIPTION (provided by applicant): Colorectal cancer has the second highest mortality rate of all cancers and recent studies indicate that increasing the amount of plant-based foods in the diet could prevent 70% of colorectal cancers. Rice bran can prevent colonic tumor development in carcinogen-induced colon cancer models and promote cell death of human colon cancer cells, however little is known regarding the interactions between rice bran phytochemicals and intestinal microbes as a mechanism to elicit these preventive effects. Bioactive rice bran components may reduce inflammation as they are novel substrates for colonic microorganisms that produce short chain fatty acids (SCFA) and other anti-inflammatory metabolites. Chemopreventive rice bran chemicals include, but are not limited to phytate, gamma-oryzanol, ferulate and phytosterols and phenolics. The mechanisms of gut fermentation and microbial metabolic by-products resulting from dietary rice bran intake have not been previously examined for colonic chemoprevention. A significant gap in our knowledge exists regarding the microbial metabolites produced following dietary rice bran intake. We hypothesize that rice bran phytochemicals will stimulate populations of beneficial microbes in the colon that produce anti-inflammatory SCFA and/or metabolize rice bran components, such as gamma-oryzanol to its bioactive metabolite ferulic acid via the activity of microbial ferulate esterases. The proposed research project will identify the change in microbes and metabolites found in stool using 454 pyrosequencing, qPCR, and metabolomics techniques. Examination of changes in bacterial flora that alter metabolism of rice bran components will advance our understanding of the dietary potential for rice bran consumption to reduce colon cancer risk. Advances in high-throughput DNA sequencing and microbe-specific data analysis tools allows for culture-independent comparisons between diverse human fecal samples and for defining changes in microbes from numerous genera. Integrating this information with changes in the fecal metabolome represents an innovative approach for determining how rice bran chemicals mitigate and/or prevent colonic inflammation. The collection of stool samples following increased rice bran intake (30 g/day for 28 days) or placebo control intake in colon cancer survivors is proposed in Aim 1, and we will determine how daily rice bran intake modulates fecal microbial community structure in Aim 2. Aim 3 will examine fecal metabolites from rice bran intake compared to control levels and will assess the effects of fecal metabolite extracts on colon cancer viability. Major outcomes from this study will be the identification of specific gut microbes and metabolites modulated by dietary rice bran intake. These findings will serve as critical, pilot data on rice bran-mediated changes in microbial metabolism for a definitive, mechanism based chemopreventive rice bran-microbe- metabolite investigation using a R01 mechanism. PUBLIC HEALTH RELEVANCE: Colorectal cancer has the second highest mortality rate of all cancers and dietary intervention with rice bran components represents a promising opportunity for chemoprevention in humans. Dietary rice bran inhibits colon tumorigenesis in animal studies, but little is known regarding the effects of dietary rice bran intake in humans for reducing coloni inflammation directly or through metabolic by-products resulting from gut fermentation. Rice bran is a readily available agricultural by-product that is not yet widely consumed by humans. Clinical investigations into anti-inflammatory activity of rice bran phytochemicals, their biotransformation products, and microbial metabolites whose production is stimulated by rice bran consumption can help to advance the inclusion of rice bran as an agent to inhibit colonic inflammation and for widespread colorectal cancer prevention.

描述（由申请人提供）：结直肠癌是所有癌症中死亡率第二高的癌症，最近的研究表明，增加饮食中植物性食物的含量可以预防 70% 的结直肠癌。米糠可以预防致癌物诱导的结肠癌模型中结肠肿瘤的发展，并促进人类结肠癌细胞的细胞死亡，但对于米糠植物化学物质与肠道微生物之间的相互作用作为引发这些预防作用的机制知之甚少。生物活性米糠成分可以减轻炎症，因为它们是产生短链脂肪酸 (SCFA) 和其他抗炎代谢物的结肠微生物的新底物。化学预防米糠化学物质包括但不限于植酸盐、γ-谷维素、阿魏酸盐、植物甾醇和酚类。此前尚未研究过膳食米糠摄入引起的肠道发酵和微生物代谢副产物的机制是否可用于结肠化学预防。关于膳食米糠摄入后产生的微生物代谢物，我们的知识存在重大差距。我们假设米糠植物化学物质会刺激结肠中的有益微生物群，这些微生物产生抗炎 SCFA 和/或通过微生物阿魏酸酯酶的活性将米糠成分（例如 γ-谷维素）代谢为其生物活性代谢物阿魏酸。 拟议的研究项目将利用 454 焦磷酸测序、qPCR 和代谢组学技术来确定粪便中微生物和代谢物的变化。检查改变米糠成分代谢的细菌菌群变化将加深我们对食用米糠降低结肠癌风险的饮食潜力的理解。高通量 DNA 测序和微生物特异性数据分析工具的进步允许在不同的人类粪便样本之间进行独立于培养物的比较，并确定多个属的微生物的变化。将这些信息与粪便代谢组的变化相结合，代表了一种确定米糠化学物质如何减轻和/或预防结肠炎症的创新方法。目标 1 提议在结肠癌幸存者增加米糠摄入量（每天 30 克，持续 28 天）或安慰剂对照摄入量后收集粪便样本，我们将在目标 2 中确定每日米糠摄入量如何调节粪便微生物群落结构。目标 3 将检查米糠摄入量的粪便代谢物与对照水平相比，并将评估粪便代谢物提取物对结肠癌生存力的影响。这项研究的主要成果将是确定受膳食米糠摄入量调节的特定肠道微生物和代谢物。这些发现将作为米糠介导的微生物代谢变化的关键试点数据，用于使用 R01 机制进行明确的、基于机制的化学预防米糠-微生物代谢物研究。 公共健康相关性：结直肠癌的死亡率位居所有癌症中第二位，米糠成分的饮食干预为人类化学预防提供了一个充满希望的机会。在动物研究中，膳食米糠可抑制结肠肿瘤的发生，但人们对膳食米糠摄入对人类直接或通过肠道发酵产生的代谢副产物减少结肠炎症的影响知之甚少。米糠是一种容易获得的农业副产品，但尚未被人类广泛消费。对米糠植物化学物质、其生物转化产物以及通过食用米糠刺激其产生的微生物代谢物的抗炎活性的临床研究，有助于推动米糠作为抑制结肠炎症和广泛预防结直肠癌的药物。