**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** SUBACUTE RUMINAL ACIDOSIS (SARA) HAS LONG BEEN CONSIDERED AN ANIMAL PRODUCTION, HEALTH, AND WELFARE ISSUE. SARA HAS HIGH INCIDENT RATES IN TWO CRITICAL PHASES IN DAIRY PRODUCTION: WEANING PERIOD IN YOUNG CALVES AND MID-LACTATION PERIOD IN DAIRY CATTLE. AS A SEQUELA TO SARA, LIVER ABSCESS CAUSES LIVER FUNCTION DAMAGE AND PREMATURE CULLING. CURRENTLY, A WELL-DEFINED, ACCURATE DIAGNOSTIC TOOL IS LACKING FOR THE DIAGNOSIS AND PREVENTION OF SARA AND ITS SUBSEQUENT LIVER ABSCESS IN CATTLE.DECREASED RUMINAL PH DURING SARA DAMAGES THE GUT EPITHELIAL AND SUBSEQUENTLY COMPROMISES BARRIER FUNCTION, ALLOWING THE TRANSLOCATION OF GUT MICROBES INTO THE BLOOD STREAM AND LEADING TO A SYSTEM-WIDE INFLAMMATORY RESPONSE AND METABOLIC ACIDOSIS. IN THIS STUDY, WE FOCUS ON THE MICROBIAL CHANGES IN TWO MAJOR TISSUE TYPES, LIVER AND BLOOD MICROBIOME (LBM), AND THEIR RELATION TO RUMINAL ACIDOSIS. USING METATRANSCRIPTOMICS AS THE MAIN APPROACH, THE OVERARCHING GOALS OF OUR PROPOSAL ARE 1) TO INVESTIGATE MEMBERSHIP AND LONGITUDINAL SHIFTS IN THE LBM; AND 2) TO ESTABLISH A CORRELATION BETWEEN LBM AND FEED-INDUCED ACIDOSIS DURING THE WEANING PERIOD IN YOUNG CALVES AND THE MID-LACTATION IN ADULT COWS. IDENTIFICATION OF A DYNAMIC AND RESPONSIVE LBM WILL BE TRANSFORMATIVE FOR DELINEATING MOLECULAR MECHANISMS INFLUENCED BY THE GUT MICROBIOME THAT IMPACT CATTLE NUTRITIONAL AND PHYSIOLOGICAL FUNCTIONS. THE EXPECTED ASSOCIATIONS BETWEEN LBM CHANGES AND FEED-INDUCED ACIDOSIS RESULTANT FROM THIS PROJECT WILL GREATLY ADVANCE INVESTIGATIONS INTO THE CAUSATIVE ROLE OF HOST-MICROBE INTERACTIONS IN PREDISPOSITION TO AND DEVELOPMENT OF SARA IN DAIRY CATTLE.