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.

PUBLIC HEALTH RELEVANCE: Colorectal cancer is the third leading cause of cancer death in men and women in the United States. An average of about 6 people die every hour of colorectal cancer and approximately 150,000 new cases are diagnosed annually. Colitis-associated colorectal cancer (CAC) represents a major form of cancer and a serious medical complication for patients suffering from inflammatory bowel disease (IBD). The economic burden for inflammatory bowel diseases (IBD) treatment is significant with annual costs in the United States estimated to be $6.3 billion. Despite this health and socio-economical burden, limited therapeutic options are currently available to prevent/treat colorectal cancer. Consumption of tea has been associated with many health benefits including the prevention of cancer and heart disease. This project investigates the role of bacteria on metabolites production derived from black tea polyphenols and their functional consequences on the development of CAC. This knowledge could be utilized to improve biotransformation of food and to prevent/treat colorectal cancer. In addition, the basic knowledge gained from the interplay between microorganisms and dietary-derived metabolite productions could uncover novel enzymes activity and therapeutic targets.