WHILE THERE IS BROAD CONSENSUS ON WHICH FOODS ARE HEALTHY, THE MOLECULAR BASIS OF THESE HEALTH BENEFITS HAS BEEN ELUSIVE. OUR MECHANISTIC UNDERSTANDING OF ALMOST EVERY FDA-APPROVED SMALL MOLECULE OR BIOLOGIC DWARFS THAT OF DRUG-LIKE MOLECULES THAT ARE ABUNDANT IN FOOD AND OF WHICH WE CONSUME TENS OF MILLIGRAMS TO GRAMS AT EVERY MEAL. THE PURPOSE OF THIS PROJECT IS TO DETERMINE HOW THE MICROBIOME-DEPENDENT PROCESSING OF GLUCOSINOLATES FROM BRASSICAS (E.G., BROCCOLI) AND STEROIDAL SAPONINS FROM SOLANACEOUS PLANTS (E.G., TOMATO) IMPACTS THE HUMAN CONSUMER. THESE COMPOUNDS UNDERGO METABOLISM BY THE GUT MICROBIOTA AND ARE ASSOCIATED WITH NUMEROUS HOST OUTCOMES (E.G. CANCER PREVENTION). IN THIS PROJECT, WE WILL FIRST DETERMINE WHICH STRAINS AND GENES FROM THE MICROBIOME METABOLIZE THESE MOLECULES INTO THEIR ACTIVE FORM (AIM 1). WE WILL THEN USE GNOTOBIOTIC MICE COLONIZED BY DEFINED MICROBIAL COMMUNITIES TO DETERMINE THE IMPACT OF THE PROCESSED DIETARY METABOLITES ON GUT MICROBIOME COMPOSITION (AIM 2) AND HOST OUTCOMES (AIM 3 & 4). OUR RECENT DATA ON THE PROCESSING OF FOOD MOLECULES BY THE MICROBIOME, COMBINED WITH OUR EXPERTISE IN ENGINEERING METABOLIC PATHWAYS IN CROP PLANTS, MAKE US WELL SUITED TO USE QUANTITATIVE METHODS TO STUDY THE METABOLISM AND BIOLOGY OF DIETARY MOLECULES IN A WHOLE FOOD CONTEXT. WE ANTICIPATE THAT THIS PROJECT WILL HELP ELUCIDATE HOW ABUNDANT MOLECULES IN FOOD INFLUENCE HUMAN HEALTH AT THE LEVEL OF MOLECULAR MECHANISM, AND ENABLE FUTURE EFFORTS TO USE DEFINED PROBIOTICS AND ENGINEERING OR BREEDING TO OPTIMIZE THE NUTRIENT CONTENT IN CROP PLANTS FOR DISEASE PREVENTION.

The Leland Stanford Junior University

Investigators