** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** THIS RESEARCH PROJECT AIMS TO INVESTIGATE A WHOLE FOOD'S EFFECT ON THE GUT MICROBIOME TO IMPROVE HUMAN HEALTH AND ADVANCE THE NUTRITION FIELD BY DETERMINING THE ROLE OF WHOLE FOOD IN CHRONIC DISEASE. WE AIM TO INVESTIGATE THE ROLE OF THE MICROBIOME IN MEDIATING THE RENAL PROTECTIVE EFFECTS OF WHOLE OATS IN TYPE 2 DIABETES. DIABETES IS THE MOST PREVALENT CAUSE OF END-STAGE RENAL KIDNEY DISEASE IN THE WORLD. OUR RESEARCH GROUP HAS DEMONSTRATED THAT RESISTANT STARCH, A LOW GLYCEMIC INDEX CARBOHYDRATE HIGH IN FERMENTABLE FIBER, ATTENUATED THE PROGRESSION OF DIABETIC NEPHROPATHY. THE POSSIBLE BENEFITS OF RESISTANT STARCH CONSUMPTION FOR THE INHIBITION OF DIABETIC NEPHROPATHY ARE PROMISING, YET REGULAR CONSUMPTION OF THIS FIBER MAY NOT BE SUSTAINABLE DUE TO PALATABILITY ISSUES. WHOLE OATS REPRESENT A FERMENTABLE LOW GLYCEMIC CARBOHYDRATE SOURCE THAT IS MORE PALATABLE AND PRODUCES A FAVORABLE GLYCEMIC RESPONSE IN DIABETICS. THE IMPACT OF OATS ON NEPHROPROTECTION AND WHETHER THE MICROBIOME MEDIATES THIS EFFECT ARE UNCLEAR.TO TACKLE THIS ISSUE, WE PLAN TO COMPLETE TWO PRE-CLINICAL STUDIES, WHERE TYPE 2 DIABETIC RATS WILL CONSUME A DIET HIGH IN WHOLE OATS TO DETERMINE WHETHER THEIR FERMENTATION BY THE GUT MICROBIOME CAN ATTENUATE KIDNEY DISEASE, COMPARED TO A CONTROL GROUP. SERUM, FECES, AND TISSUES WILL BE COLLECTED AFTER AN EIGHT-WEEK FEEDING STUDY, AND RENAL FUNCTION WILL BE ASSESSED TO DETERMINE THE EFFECT OF WHOLE OATS ON DIABETIC NEPHROPATHY. DEPENDING ON OUR RESULTS, WE WILL FOLLOW UP THIS STUDY WITH A FECAL MICROBIOTA TRANSPLANTATION STUDY, WHERE RECIPIENT RATS WILL RECEIVE FECAL MATERIAL FROM DIABETIC DONORS FED WITH WHOLE OATS AND RESISTANT STARCH TO ASSESS IF THE GUT MICROBIOME MEDIATES THE NEPHROPROTECTIVE EFFECTS. WE ALSO PLAN TO DEMONSTRATE THAT THIS DIETARY INTERVENTION IS FEASIBLE FOR TRANSLATIONAL STUDIES, AS WE WILL UTILIZE MODERATE LEVELS OF WHOLE OATS AND RESISTANT STARCH IN THE PROPOSED STUDIES. UNDERSTANDING THE ROLE OF WHOLE FOOD IN IMPROVING THE PROGRESSION OF SUCH PREVALENT DISEASE WILL PROVIDE A NOVEL UNDERSTANDING OF THE NEPHROPROTECTIVE MECHANISMS OF ACTIONS OF DIETARY WHOLE OATS AND RESISTANT STARCH TO THE NUTRITIONAL SCIENCE FIELD.