THIS PROJECT ADDRESSES AN IMPORTANT CHALLENGE AREA OF NANOTOXICOLOGY- DETAILED UNDERSTANDING OF MOLECULAR MECHANISM BY WHICH ENGINEERED NPS INDUCE POTENTIAL ADVERSE EFFECTS. THERE HAS BEEN INCREASING CONCERN ABOUT THE POTENTIAL HEALTH RISKS ASSOCIATED WITH FOODBORNE INORGANIC NANOPARTICLES (NPS) SUCH AS TITANIUM DIOXIDE NPS. GUT MICROBIOTA HAVE BEEN SHOWN TO PLAY IMPORTANT ROLES IN HUMAN HEALTH. DISRUPTION OF THE GUT MICROBIOTA (DYSBIOSIS) IS ASSOCIATED WITH NUMEROUS ADVERSE EFFECTS. OUR PRELIMINARY STUDIES DEMONSTRATED THAT FOODBORNE TITANIUM DIOXIDE NPS SIGNIFICANTLY ALTERED THE COMPOSITION OF GUT MICROBIOTA IN MICE, WHICH DIRECTLY RESULTED IN INFLAMMATORY PATHOLOGICAL CHANGES IN THE COLON. THESE ADVERSE EFFECTS OF TITANIUM DIOXIDE NPS WERE STRONGER IN OBESE MICE THAN NON-OBESE MICE. THIS FINDING IS IMPORTANT BECAUSE IT PROVIDED A NOVEL MECHANISM BY WHICH FOODBORNE TITANIUM DIOXIDE NPS INDUCE POTENTIAL ADVERSE EFFECTS. TO ADDRESS THE LACK OF KNOWLEDGE ON THE MECHANISM OF POTENTIAL TOXICITY OF FOODBORNE TITANIUM DIOXIDE NPS, BASED ON OUR PRELIMINARY DATA, THE OVERALL OBJECTIVE OF THIS PROJECT IS TO DETERMINE THE EFFECTS OF FOODBORNE TITANIUM DIOXIDE NPS IN ALTERING GUT MICROBIOTA, AND ELUCIDATE THE ROLE OF ALTERED GUT MICROBIOTA IN MEDIATING THE POTENTIAL ADVERSE EFFECTS CAUSED BY TITANIUM DIOXIDE NPS. THE SIGNIFICANCE OF THE PROPOSED RESEARCH IS THAT IT WILL PROVIDE DETAILED INFORMATION THAT IS CURRENTLY LACKING THE ROLE OF ALTERED GUT MICROBIOTA IN MEDIATING THE ADVERSE EFFECTS OF FOODBORNE TITANIUM DIOXIDE NPS. THIS INFORMATION IS CRITICALLY IMPORTANT FOR ENSURING THE SAFETY OF A WIDE RANGE OF FOOD PRODUCTS THAT MAY CONTAIN TITANIUM DIOXIDE NPS. A PARTICULARLY INNOVATIVE ASPECT OF THIS PROJECT IS THAT IT AIMS TO DETERMINE THE IMPACT OF THE TITANIUM DIOXIDE NPS IN DIFFERENT POPULATIONS INCLUDE THOSE POTENTIALLY MORE SUSCEPTIBLE TO THE POTENTIAL ADVERSE EFFECTS OF TITANIUM DIOXIDE NPS, SUCH AS CHILDREN AND OBESE INDIVIDUALS.