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.

描述（由申请人提供）：大肠癌的死亡率是所有癌症的第二高死亡率，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。米麸可以预防致癌物诱导的结肠癌模型的结肠肿瘤发展并促进人类结肠癌细胞的细胞死亡，但是，对于水稻麸皮植物化学物质和肠道微生物之间的相互作用，知之甚少，这是一种引起这些预防作用的机制。生物活性米麸组成分可能会减少炎症，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型底物。化学预防水稻麸皮化学物质包括但不限于植酸，γ-果丹醇，禁食和植物固醇和酚类。先前尚未检查饮食中麸皮摄入量引起的肠道发酵和微生物代谢副产品的机制。关于饮食米麸摄入后产生的微生物代谢产生的微生物代谢产生的微生物代谢物存在很大的差距。我们假设米麸的植物化学物质将刺激结肠中有益微生物的种群，产生抗炎的SCFA和/或代谢米Bran成分，例如γ-鸟烯醇，例如其生物活性代谢物，通过微生物酯酶的活性。 拟议的研究项目将使用454个焦磷酸测序，QPCR和代谢组学技术确定在粪便中发现的微生物和代谢产物的变化。检查改变米麸组成分的新陈代谢的细菌菌群变化将促进我们对饮食中消费饮食的理解，从而降低结肠癌风险。高通量DNA测序和微生物特异性数据分析工具的进展允许在各种人类粪便样本之间进行培养无关的比较，并定义了来自众多属的微生物的变化。将这些信息与粪便代谢组的变化整合在一起，代表了一种创新的方法，用于确定米麸化学物质如何减轻和/或预防结肠炎症。在AIM 1中提出了米麸摄入量增加（30 g/day的30 g/天）或安慰剂控制摄入后的粪便样品的收集，我们将确定AIM 2中的每日水稻麸皮在AIM 2中调节粪便微生物群落结构。AIM3将通过稻草摄入量与对照癌症进行癌症的效果相比，将检查乳液摄取量的粪便代谢物。这项研究的主要结果是鉴定特定的肠道微生物和由膳食米麸摄入调节的代谢物。这些发现将作为对大米麸皮介导的微生物代谢变化的关键数据，用于使用R01机制进行确定的，基于机制的化学预防水稻麸皮 - 微生物 - 代谢物研究。

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