INFLAMMATORY BOWEL DISEASE (IBD) IS A GLOBAL DISEASE THAT HAS RAPIDLY EXPANDED IN BOTH WESTERN CIVILIZATIONS AND NEWLY INDUSTRIALIZED NATIONS IN THE 21ST CENTURY. IN NORTH AMERICA, OVER 1.5 MILLION PEOPLE SUFFER FROM IBD, WHICH INCLUDES ULCERATIVE COLITIS (UC) AND CROHN'S DISEASE (CD). CHANGES IN ENVIRONMENTAL AND LIFESTYLE FACTORS COINCIDING WITH WESTERNIZATION HAS DRIVEN A RAPID ACCELERATION IN IBD PREVALENCE WORLDWIDE. THE GUT MICROBIOME AS WELL AS HOST IMMUNE RESPONSE AND GUT BARRIER FUNCTION APPEAR TO CONTRIBUTE TO IBD, VIA INCREASING INTESTINAL INFLAMMATION AND COLITIS. THUS, THERE IS A CRITICAL NEED TO IDENTIFY THERAPEUTIC STRATEGIES AIMED AT IMPROVING GUT HEALTH AND HOST-MICROBIOTA INTERACTIONS IN THE MANAGEMENT OF IBD. THE EFFECTS OF DAIRY LIPIDS ON IBD IS CONTROVERSIAL, AS SOME EVIDENCE SUGGESTS MILK FAT EXACERBATES COLITIS IN MICE, WHILE MILK SPHINGOMYELIN (SM) (A TYPE OF MILK POLAR LIPID) PROTECTS AGAINST COLITIS. A RECENT OBSERVATIONAL STUDY FAILED TO FIND ANY NEGATIVE IMPACT OF DAIRY PRODUCTS ON IBD INCIDENCE, WITH MILK CONSUMPTION ACTUALLY BEING PROTECTIVE AGAINST CD. MILK FAT GLOBULES ARE NATURALLY ENCASED IN MILK FAT GLOBULE MEMBRANE (MFGM), A STRUCTURE RICH IN POLAR LIPIDS, LIKE SM. HOWEVER, DAIRY PRODUCTION PROCESSES RESULT IN VARIABLE MILK POLAR LIPID (MPL) CONTENT OF DAIRY PRODUCTS, WITH SOME UNDERUTILIZED DAIRY CO-PRODUCTS, SUCH AS BUTTER SERUM AND BUTTERMILK, BEING RICH SOURCES OF MPLS. WE HAVE REPORTED THAT MILK SM BENEFICIALLY MODULATES GUT MICROBIOTA AND IS ANTI-INFLAMMATORY. PRELIMINARY DATA FROM OUR RESEARCH GROUP ALSO SHOWS MPL-FED MICE HAVE INCREASES IN GUT MICROBIOTA DIVERSITY AND BENEFICIAL GUT MICROBE POPULATIONS. THUS, DAIRY LIPIDS APPEAR TO HAVE DIFFERENTIAL EFFECTS ON COLITIS; HOWEVER, THE UNDERLYING MECHANISMS, INTERACTIONS BETWEEN LIPIDS, AND THE ROLE OF GUT MICROBIOTA ARE UNCLEAR. IN THIS PROJECT, WE PLAN TO 1) DETERMINE THE EFFECTS OF MPLS AND MILK FAT ON COLITIS DEVELOPMENT IN MICE AND THE DEPENDENCE ON GUT BACTERIA, AND 2) EVALUATE THE UNDERLYING MECHANISMS AT PLAY. THERE IS A CLEAR GAP IN THE SCIENTIFIC KNOWLEDGE REGARDING THE ROLE THAT DAIRY LIPIDS MAY PLAY IN COLITIS DEVELOPMENT, ESPECIALLY IN REGARDS TO INTERACTIONS OF MPLS AND MILK FAT IN THE DIET, UNDERLYING MECHANISMS INVOLVED, AND DEPENDENCE ON GUT MICROBIOTA. THIS PROJECT SERVES AS THE FIRST ATTEMPT AT UNDERSTANDING HOW DAIRY LIPIDS INTERACT WITH GUT MICROBIOTA TO INFLUENCE COLON HEALTH, AS WELL AS PROVIDE NOVEL INSIGHT INTO MECHANISMS INVOLVED VIA EMPLOYING TRANSCRIPTOMICS ANALYSIS. SUCH BASIC SCIENCE RESEARCH MAY PROVIDE THE IMPETUS FOR CLINICAL TRIALS INVESTIGATING MPLS IN IBD PATIENTS AND PROMOTE THE CONSUMPTION OF MPL-RICH MILK AND DAIRY PRODUCTS. FURTHERMORE, INEXPENSIVE DAIRY CO-PRODUCTS RICH IN MPLS, SUCH AS BUTTER SERUM OR BUTTERMILK, COULD BE PROMOTED AND UTILIZED AS VALUE-ADDED SOURCES OF THESE BIOACTIVE LIPIDS.