Impact of microbiota-mediated biotransformation of black tea polyphenols

微生物介导的红茶多酚生物转化的影响

基本信息

批准号：
8825636
负责人：
Christian Jobin
金额：
$ 47.85万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-01-01 至 2019-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8825636
关键词：
Accounting Acids Address Animals Anti-Inflammatory Agents Anti-inflammatory Apoptosis Bacteria Beverages Bilateral Biological Biological Availability Biological Process Biota Black Tea Cancer Etiology Catechin Cell Proliferation Cessation of life Chemopreventive Agent Colitis Colonic Neoplasms Colorectal Cancer Complex Consumption Data Development Diagnosis Diet Drug Kinetics Economic Burden Enterococcus faecalis Environmental Risk Factor Escherichia coli Excretory function Food Gallic acid Generations Germ-Free Gnotobiotic Goals Health Health Benefit Heart Diseases Hour Housing Human In Vitro Individual Inflammatory Bowel Diseases Intestines Knowledge Location Malignant Neoplasms Measures Mediating Metabolic Metabolic Biotransformation Metabolism Microbe Modeling Molecular Weight Mono-S Mus Oral Organ Organism Pathology Patients Plasma Play Polymers Positioning Attribute Preventive Process Production RNA Sequences Reporting Resources Ribosomal RNA Role Sampling Signal Transduction Specific Pathogen Frees System Tea Theaflavins Therapeutic Tissues United States Urine Wild Type Mouse Woman absorption cancer prevention colon cancer cell line commensal microbes cost dimer enzyme activity expectation germ free condition gut microbiota improved inflammatory marker insight intestinal homeostasis liquid chromatography mass spectrometry medical complication men metabolomics microbial microbial community microbiome microorganism novel phenolic acid polyphenol prevent public health relevance therapeutic target transcriptome sequencing

项目摘要

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.

描述（由适用提供）：茶是世界上最广泛的早餐之一，红茶占生产的78％。茶的消费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，茶多酚在内，包括角肠，它们的二聚体（曲霉）和聚合物（Thearubigins）具有抗炎和癌症预防活性。然而，红茶中主要的多酚曲霉和曲木素的系统生物利用度较差。因此，尚不清楚这些化合物如何发挥其生物学功能。研究表明，较高的分子量多酚是由菌群代谢的，其代谢物可能在红茶化学预防作用中起重要作用。环形产物和较低的分子量苯酚酸已经被确定为近叶蛋白的主要细菌代谢产物。然而，黄曲霉素和硫脂素的细菌代谢产物仍然未知。我们的初步数据表明，微生物衍生的代谢产物是由茶酚曲霉蛋白产生的。我们的中心假设是，菌群会影响红茶多酚衍生的代谢产物的产生，从而增强了其生物利用度和生物学活性。该项目的目的是确定细菌与多酚代谢之间的串扰，并确定对结肠炎相关结直肠癌发展的功能后果。我们的具体目的如下：1）确定选择性微生物群对黑茶多酚衍生代谢产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产物与红茶多酚/代谢物在结肠炎相关的结直肠癌中的生物学作用之间的关系。 3）测量黑茶多酚对微生物群落组成和活动的影响。该项目将确定菌群对IL10 - / - 小鼠中红茶多酚介导的生物学作用的影响。由于微生物群落在个体之间是可变的，因此我们的发现将提供有关微生物如何改变定义的饮食产物生物学活性的新见解。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学活性。另外，基本从微生物与饮食衍生的代谢产物生产之间的相互作用中获得的知识可能会发现新颖的酶活性和治疗靶标。