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: 8517050
• 负责人: Elizabeth P Ryan
• 金额: $ 14.86万
• 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/8517050
• 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; 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; intestinal homeostasis; metabolomics; microbial; microbial community; microbiome; microorganism; mortality; multidisciplinary; novel; phenolic acid; phytate; prevent; pyrosequencing; 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.

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数量可以预防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，然而关于米糠植物化学物质和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少炎症，因为它们是产生短链脂肪酸（SCFA）和其他抗炎代谢产物的结肠微生物的新底物。化学预防米糠化学品包括但不限于植酸盐、γ-谷维素、阿魏酸盐和植物甾醇和酚类。肠道发酵和微生物代谢副产物的机制，导致膳食米糠摄入量以前没有检查结肠化学预防。我们的知识中存在着一个显着的差距，关于饮食米糠摄入后产生的微生物代谢产物。我们假设米糠植物化学物质将刺激结肠中的有益微生物群体，其产生抗炎SCFA和/或代谢米糠组分，例如γ-谷维素通过微生物阿魏酸酯酶的活性代谢成其生物活性代谢物阿魏酸。 拟议的研究项目将使用454焦磷酸测序，qPCR和代谢组学技术来确定粪便中发现的微生物和代谢物的变化。检查改变米糠成分代谢的细菌植物群的变化将促进我们对米糠消费的饮食潜力的理解，以降低结肠癌的风险。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的比较，并定义来自许多属的微生物的变化。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中提出了在结肠癌幸存者中增加米糠摄入量（30 g/天，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将检查来自米糠摄入的粪便代谢物与对照水平的比较，并将评估粪便代谢物提取物对结肠癌存活率的影响。本研究的主要结果将是确定特定的肠道微生物和代谢产物的饮食米糠摄入量调制。这些研究结果将作为关键的，试点数据米糠介导的微生物代谢的变化，一个明确的，基于机制的化学预防米糠微生物代谢物的调查使用R 01机制。

项目成果

Modulation of plasma and urine metabolome in colorectal cancer survivors consuming rice bran.

食用米糠的结直肠癌幸存者血浆和尿液代谢组的调节。

• DOI: 10.15761/ifnm.1000252
• 发表时间: 2019
• 期刊: Integrative food, nutrition and metabolism
• 作者: Zarei,Iman;Oppel,ReneeC;Borresen,EricaC;Brown,ReginaJ;Ryan,ElizabethP
• 通讯作者: Ryan,ElizabethP

Diet and the development of the human intestinal microbiome.

• DOI: 10.3389/fmicb.2014.00494
• 发表时间: 2014
• 期刊: Frontiers in microbiology
• 影响因子: 5.2
• 作者: Voreades N;Kozil A;Weir TL
• 通讯作者: Weir TL

Plasma and Urine Metabolite Profiles Impacted by Increased Dietary Navy Bean Intake in Colorectal Cancer Survivors: A Randomized-Controlled Trial.

• DOI: 10.1158/1940-6207.capr-20-0270
• 发表时间: 2021-04
• 期刊: Cancer prevention research (Philadelphia, Pa.)
• 作者: Zarei I;Baxter BA;Oppel RC;Borresen EC;Brown RJ;Ryan EP
• 通讯作者: Ryan EP

Cancer-promoting effects of microbial dysbiosis.

• DOI: 10.1007/s11912-014-0406-0
• 发表时间: 2014-10
• 期刊: CURRENT ONCOLOGY REPORTS
• 影响因子: 4.7
• 作者: Sheflin, Amy M.;Whitney, Alyssa K.;Weir, Tiffany L.
• 通讯作者: Weir, Tiffany L.

Pilot dietary intervention with heat-stabilized rice bran modulates stool microbiota and metabolites in healthy adults.

• DOI: 10.3390/nu7021282
• 发表时间: 2015-02-16
• 期刊: Nutrients
• 影响因子: 5.9
• 作者: Sheflin AM;Borresen EC;Wdowik MJ;Rao S;Brown RJ;Heuberger AL;Broeckling CD;Weir TL;Ryan EP
• 通讯作者: Ryan EP