Impact of microbiota-mediated biotransformation of black tea polyphenols

 描述（申请人提供）：茶是世界上消费最广泛的饮料之一，红茶占产量的78%。喝茶与许多健康益处有关，包括预防癌症和心脏病。这些作用归因于茶中存在的多酚化合物。大量研究表明，茶多酚包括儿茶素、其二聚体（茶黄素）和聚合物（茶红素），具有抗炎和预防癌症的活性。然而，红茶中的主要多酚类物质茶黄素和茶红素的系统生物利用度较差。因此，目前还不清楚这些化合物如何发挥其生物学功能。研究表明，较高分子量的多酚被微生物群代谢，其代谢产物可能在红茶的化学预防作用中发挥重要作用。环分裂产物和低分子量酚酸已被确定为儿茶素的主要细菌代谢产物。然而，茶黄素和茶红素的细菌代谢产物仍然是未知的。我们的初步数据表明，微生物衍生的代谢产物产生的茶多酚茶红素。我们的中心假设是，微生物群影响红茶多酚衍生代谢物的产生，提高其生物利用度和生物活性。该项目的目标是确定细菌和多酚代谢之间的串扰，并建立结肠炎相关结直肠癌发展的功能后果。本研究的具体目标如下：1）确定选择性微生物群对红茶多酚衍生代谢物的生物转化和药代动力学的影响。2)确定微生物衍生的代谢物和黑茶多酚/代谢物在结肠炎相关结直肠癌中的生物学作用之间的关系。3)测量红茶多酚对微生物群落组成和活性的影响。本项目将在Il 10-/-小鼠中确定微生物群对红茶多酚介导的生物效应的影响。由于微生物群落在个体之间是可变的，我们的研究结果将为微生物如何改变特定膳食产品的生物活性提供新的见解。这些知识可用于改善活性食品的生物转化，并增强其在包括肠道在内的各种器官中的生物活性。且基本 从微生物和饮食衍生的代谢产物之间的相互作用中获得的知识可以发现新的酶活性和治疗靶点。

 DESCRIPTION (provided by applicant): Tea is one of the most widely consumed beverages in the world, with black tea accounting for 78% of the production. Consumption of tea has been associated with many health benefits including the prevention of cancer and heart disease. These effects have been attributed to the polyphenol compounds present in tea. Numerous studies have shown that tea polyphenols including catechins, their dimers (theaflavins) and polymers (thearubigins), have anti-inflammatory and cancer preventive activities. However, theaflavins and thearubigins, the major polyphenols in black tea, have poor systematic bioavailability. Therefore, it is still unclear how these compounds could exert their biological functions. Studies have shown that higher molecular weight polyphenols are metabolized by the microbiota and their metabolites may play an important role in black tea chemopreventive action. Ring-fission products and lower molecular weight phenolic acids have been identified as the major bacterial metabolites of catechins. However, the bacterial metabolites of theaflavins and thearubigins are still unknown. Our preliminary data indicate that microbial-derived metabolites are generated from the tea polyphenol thearubigins. Our central hypothesis is that the microbiota influence the generation of black tea polyphenol-derived metabolites enhancing their bioavailability and biological activities. The goal of this project is to determine the crosstalk between bacteria and polyphenol metabolism and establish the functional consequences on development of colitis-associated colorectal cancer. Our specific aims are as follows: 1) Determine the impact of the selective microbiota on biotransformation and pharmacokinetics of black tea polyphenol-derived metabolites. 2) Determine the relationship between microbial-derived metabolites and the biological action of black tea polyphenols/metabolites in colitis-associated colorectal cancer. 3) Measure the impact of black tea polyphenols on microbial community composition and activities. This project will determine the impact of the microbiota on black tea polyphenol- mediated biological effect in Il10-/- mice. Since the microbial community is variable among individuals, our findings will provide novel insight into how the biological activity of a defined dietary product could be altered by microorganisms. This knowledge could be utilized to improve biotransformation of active food products and to enhance their biological activity in various organs including the intestine. In addition, the basic knowledge gained from the interplay between microorganisms and dietary-derived metabolite productions could uncover novel enzymes activity and therapeutic targets.