TEA IS THE MOST ABUNDANTLY CONSUMED PREPARED BEVERAGE IN THE WORLD. GREEN TEA, CONTAINING BIOACTIVE CATECHINS, EXERTS ANTIINFLAMMATORY ACTIVITIES. HOWEVER, A FUNDAMENTAL GAP EXISTS CONCERNING ITS INTESTINAL-LEVEL TARGETS THAT CAN PREVENT THE DEVELOPMENT AND PROGRESSION OF METABOLIC SYNDROME (METS). OUR PRELIMINARY DATA DEMONSTRATE THAT GREEN TEA INHIBITS INFLAMMATION (E.G. NFΚB ACTIVATION) IN OBESE RODENTS BY LIMITING THE TRANSLOCATION OF GUT-DERIVED ENDOTOXIN (I.E. A COMPONENT OF THE MEMBRANCE FROM CERTAIN BACTERIA)TO THE PORTAL CIRCULATION AND DECREASING LIVER PRO-INFLAMMATORY DAMAGE ATTRIBUTED TO TOLL-LIKE RECEPTOR-4 (TLR4), A RECEPTOR THAT BINDS ENDOTOXINS. IN HUMANS, GREEN TEA ALSO DECREASES INTESTINAL PERMEABILITY. THE OBJECTIVE OF THIS PROJECT IS TO ESTABLISH EVIDENCE-BASED RECOMMENDATIONS FOR GREEN TEA, BASED ON IMPROVEMENTS IN ENDOTOXEMIA AND RESTORED GUT BARRIER FUNCTION, THAT PROMOTE OPTIMAL HEALTH. THE HYPOTHESIS IS THAT GREEN TEA CATECHINS FUNCTION TO LIMIT METABOLIC ENDOTOXEMIA BY AMELIORATING GUT DYSBIOSIS (ALTERED POPULATIONS OF GUT BACTERIA)-MEDIATED INFLAMMATION THAT OTHERWISE PROVOKES INTESTINAL PERMEABILITY. THE SPECIFIC AIMS INCLUDE: 1) TRANSLATING INTESTINAL-LEVEL BENEFITS OF GREEN TEA CATECHINS; AND 2) DEFINING ANTIINFLAMMATORY CATECHIN-MICROBIOTA INTERACTIONS. THE PLANNED APPROACH INCLUDES A DOUBLE-BLIND, PLACEBO-CONTROLLED, RANDOMIZED CROSSOVER TRIAL IN METS AND HEALTHY PERSONS TO EXAMINE THE EFFICACY OF GREEN TEA ON METABOLIC ENDOTOXEMIA. SEPARATE STUDIES IN A HUMAN COLONIC MODEL WILL ESTABLISH CATECHIN-SPECIFIC BENEFITS ON MICROBIOTA FUNCTION TO GENERATE ANTIINFLAMMATORY METABOLITES. THE INTEGRATION OF BIOMOLECULAR, METAGENOMICS, AND METABOLOMICS ASPECTS WILL DEFINE ANTIINFLAMMATORY BIOACTIVITIES OF CATECHINS, EITHER DIRECTLY AND/OR INDIRECTLY FROM MICROBIAL-DERIVED METABOLITES, THAT LIMIT ENDOTOXIN TRANSLOCATION AND CONSEQUENT TLR4/NFΚB INFLAMMATION. THE ANTICIPATED OUTCOMES ARE EXPECTED TO BE OF SIGNIFICANCE, BECAUSE THEY WILL SUBSTANTIALLY ADVANCE A CRITICALLY NEEDED DIETARY STRATEGY TO AVERT METS COMPLICATIONS ATTRIBUTED TO METABOLIC ENDOTOXEMIA BY ESTABLISHING ANTIINFLAMMATORY PREBIOTIC AND ANTIMICROBIAL BIOACTIVITIES OF CATECHINS THAT PROMOTE INTESTINAL HEALTH.

Ohio State University, The, Columbus OH

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