**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** RECENT STUDIES HAVE HIGHLIGHTED THE ROLE OF THE INTESTINAL MICROBIOTA IN THE SUSCEPTIBILITY TO A NUMBER OF DISEASES INCLUDING METABOLIC SYNDROME. THE MICROBIOTA IS COMPOSED OF MILLIONS OF BACTERIA THAT HAVE PROFOUND EFFECTS ON NUTRIENT AVAILABILITY WHILE AT THE SAME TIME PRODUCING A NUMBER OF DISEASE RELATED METABOLITES, SUCH AS TRIMETHYLAMINE N-OXIDE (TMAO), WHICH WE HAVE DESCRIBED IN OUR PREVIOUS STUDIES. MANY QUESTIONS REMAIN REGARDING THE CONTRIBUTION OF THE MICROBIOME TO THE METABOLIC SYNDROME. FOR EXAMPLE WE DO NOT KNOW WHICH BACTERIA IN THE GUT ARE REGULATING METABOLIC SYNDROME SUSCEPTIBILITY AND HOW DIET INTERACTS WITH THESE BACTERIA. MOREOVER THE INCREASING PREVALENCE OF EARLY ONSET DIABETES AND CHILDHOOD OBESITY SUGGEST THAT MATERNAL FACTORS MAY BE MODULATING DISEASE RISK. WE SUGGEST THAT DISCOVERY OF SPECIFIC BACTERIA, THEIR GENE EXPRESSION PROFILES, AND NUTRIENT*MICROBIOTA INTERACTIONS ARE CRITICAL TO REFINE OUR DIETARY RECOMMENDATIONS.OUR PRELIMINARY STUDIES SUGGEST THATMATERNAL DIET MAY BE INTERACTING WITH THE MICROBIOTA TO AFFECT METABOLIC SYNDROME. IN THE PROPOSED WORK, WE CAPITALIZE UPON OUR EXPERTISE IN MOUSE GENETICS TO FURTHER UNDERSTAND THE IMPACT OF MATERNAL DIET ON METABOLIC SYNDROME SUSCEPTIBILITY IN OFFSPRING. THESE STUDIES ALLOW US TO LEVERAGE WELL-CONTROLLED EXPERIMENTS IN MICE USING THE MOST ADVANCED MOUSE GENETIC RESOURCES AVAILABLE CALLED THE COLLABORATIVE CROSS. USING A SIMPLE BREEDING SCHEME WE WILL TEST THE EFFECTS OF DIET ON MATERNAL MICROBIOTA, THE TRANSMISSION OF MICROBIOTA TO OFFSPRING AND THE EFFECTS OF THESE TRANSMITTED MICROBIOTA ON METABOLIC SYNDROME. SPECIFIC BACTERIAL GENES ARE IDENTIFIED THROUGH RNA-SEQ ANALYSIS AND TESTED IN-VIVO USING ADOPTIVE TRANSFER EXPERIMENTS.