biostudies-literatureUnknown12Ma J<h4>Purpose</h4>This study evaluated the effect of Tirzepatide on metabolic profiles, kidney function, and gut microbiota composition in mice with diabetic kidney disease (DKD) and clarify the relationship between gut microbiota alterations and the renoprotective effects.<h4>Methods</h4>Seven-week-old diabetic db/db mice and db/m controls were randomly assigned to three groups: db/db, db/db-T, and db/m. In the db/db-T group, mice received 10 nmol/kg Tirzepatide injections for a duration of 8 weeks. Biochemical and histopathological analyses were used to assess body weight, blood glucose, lipid profile, hepatic and renal function, and renal histopathological changes in mice. An antibiotic-pretreated group (ABX-db/db-T) was established to explore the impact of gut microbiome depletion on theFrontiers in molecular biosciences1715024https://www.ebi.ac.uk/biostudies/studies/S-EPMC12740902biostudies-literatureTirzepatide modulates gut microbiota homeostasis to protect against diabetic kidney disease.PMC12740902Zhang WWang MZhou LTao MLu WZhang HLi FYao DMa JfalseTirzepatide modulates gut microbiota homeostasis to protect against diabetic kidney disease.<h4>Purpose</h4>This study evaluated the effect of Tirzepatide on metabolic profiles, kidney function, and gut microbiota composition in mice with diabetic kidney disease (DKD) and clarify the relationship between gut microbiota alterations and the renoprotective effects.<h4>Methods</h4>Seven-week-old diabetic db/db mice and db/m controls were randomly assigned to three groups: db/db, db/db-T, and db/m. In the db/db-T group, mice received 10 nmol/kg Tirzepatide injections for a duration of 8 weeks. Biochemical and histopathological analyses were used to assess body weight, blood glucose, lipid profile, hepatic and renal function, and renal histopathological changes in mice. An antibiotic-pretreated group (ABX-db/db-T) was established to explore the impact of gut microbiome depletion on the2025-01-01T00:00:00Z20252026-06-06T05:53:32.229Z2026-05-27T03:11:59.286ZS-EPMC127409024145862710.3389/fmolb.2025.1715024