Probiotic Metabolism of Rice Bran Phytochemicals for Chemoprevention

描述（由申请人提供）： 虽然流行病学证据支持全谷物消费和癌症风险之间的负相关，结果是不确定的精确的生物活性食品成分发生化学预防。新出现的数据已经确定了米糠中含有的植物化学物质，可以降低癌症风险;然而，人们对这些化学预防植物化学物质在现有品种和地方品种中的浓度和生物利用度知之甚少。水稻（Oryza sativa）是一半人类的主要膳食卡路里来源，也是第一种获得高质量参考基因组序列的作物。应研究具有世界范围内驯化水稻令人印象深刻的基因型和表型多样性的水稻品种的差异性癌症预防特性。此外，对文献的广泛回顾显示，旨在探索益生菌在代谢米糠中所起作用的研究有限。因此，提出了一个实验模型的发展，以评估米糠-益生菌相互作用对血液，淋巴细胞和淋巴结的化学预防化合物的生物利用度的影响。本文提出的研究结果将填补一个显着的空白，我们的知识米糠植物化学多样性和生物利用度的化学预防。将在三个遗传多样的水稻品种中确定具有抗癌特性的选定生物活性米糠组分的化学计量。这些大米品种将与益生菌，干酪乳杆菌和双歧杆菌长，和一个居民非益生菌，大肠杆菌，在目标1中发酵，以确定其对选定的代谢物水平的影响。假设米糠的益生菌消化提高米糠衍生的化学预防化合物的生物利用度。植物化学物质和代谢物将通过液相色谱和气相色谱联用-质谱（LC-MS，GC-MS）检测。第二个目的是确定米糠的剂量，以达到最大的生物利用度的目标植物化学物质和代谢物进入血液，淋巴细胞和淋巴结的自然发生的犬淋巴瘤患者。这种比较肿瘤学模型是评估膳食米糠成分生物利用度的新方法。此外，已经充分确定，与啮齿动物中实验诱导的癌症相比，自然发展的犬癌症表现出更大的翻译潜力，特别是对于淋巴瘤。试验剂量确定研究是可行的，以测试的假设，即生物利用度的癌症预防化合物从饮食全米糠摄入量不同的遗传多样性水稻品种和益生菌发酵。事实上，评估纤维或分离米糠化合物和癌症风险的作用的临床前和临床研究是相互矛盾的，我们提出了新的跨学科科学方法是必要的，以推进米糠预防癌症的营养研究。

DESCRIPTION (provided by applicant): Although epidemiologic evidence supports an inverse association between whole grain consumption and cancer risk, results are inconclusive as to the precise bioactive food components by which chemoprevention occurs. Emerging data has identified phytochemicals contained in rice bran that may reduce cancer risk; however, little is known about the concentrations and bioavailability of these chemopreventive phytochemicals in existing varieties and landraces of cultivated rice. Rice (Oryza sativa) is the primary source of dietary calories for half of humanity and is the first crop plant for which a high-quality reference genome sequence has been produced. Rice varieties that capture the impressive genotypic and phenotypic diversity of domesticated rice world-wide should be investigated for differential cancer prevention properties. Moreover, an extensive review of the literature revealed limited research aimed at exploring the role probiotics play in metabolizing rice bran. Thus, the development of an experimental model to assess the effects of rice bran-probiotic interactions on bioavailability of chemopreventive compounds to blood, lymphocytes and lymph nodes is proposed. Findings from the studies proposed herein will fill a significant gap in our knowledge regarding rice bran phytochemical diversity and bioavailability for chemoprevention. The stoichiometry of selected bioactive rice bran components with reported cancer prevention properties will be determined in three genetically diverse rice cultivars. These rice varieties will be fermented with probiotics, Lactobacillus caseii and Bifidobacteria longum, and one resident non-probiotic, Escherichia coli, in Aim 1 to determine their effect on levels of the selected metabolites. The probiotic digestion of rice bran is hypothesized to enhance bioavailability of rice bran derived chemopreventive compounds. Phytochemicals and metabolites will be detected by liquid and gas chromatography coupled with -mass spectrometry (LC-MS, GC-MS). A second aim is proposed to determine the dose of rice bran that achieves greatest bioavailability of target phytochemicals and metabolites into blood, lymphocytes and lymph nodes of naturally occurring canine lymphoma patients. This comparative oncology model is novel for assessing bioavailability of dietary rice bran components. Furthermore, it has been well established that naturally developing canine cancer exhibits greater translational potential compared to experimentally induced cancer in rodents, particularly for lymphoma. The pilot dose determination studies are feasible for testing the hypothesis that bioavailability of cancer prevention compounds from dietary whole rice bran intake varies across genetically diverse rice cultivars and by probiotic fermentation. Indeed, pre-clinical and clinical studies that evaluate the role of fiber or isolated rice bran compounds and cancer risk are conflicting, and we put forth that novel transdisciplinary scientific approaches are necessary to advance the nutritional investigation of rice bran for cancer prevention.