Abstract
The gut microbiota plays a crucial role in regulating health and mitigating diabetes-induced liver injury. This study evaluated the hepatoprotective effects of Bifidobacterium bifidum supplementation, both alone and in combination with metformin, in a rat model of diabetes-induced liver dysfunction. Rats were divided into six groups: control, probiotic only, metformin only, diabetic, diabetic with probiotic supplementation, and diabetic with combined probiotic and metformin treatment. Diabetes was induced using a single streptozotocin (STZ) injection following a 12 h fast. Probiotic supplementation (1 × 10(9) CFU/kg daily) was initiated 2 weeks before diabetes induction and continued throughout the experiment, while metformin was administered concurrently at a therapeutic dose. Weekly assessments included fasting blood glucose, insulin levels, glycation markers, and liver function tests. Both probiotic and metformin treatments significantly improved glycemic control (p < 0.05) and reduced fasting blood glucose levels (p < 0.01), with the combined therapy demonstrating the most pronounced effects. Additionally, insulin sensitivity was enhanced (p < 0.05), antioxidant enzyme levels were restored (p < 0.01), and histopathological analyses revealed preserved liver architecture, decreased inflammation (p < 0.01), and reduced fibrosis (p < 0.05). The Comet assay confirmed a significant reduction in DNA damage (p < 0.01), indicating the protective effects of the interventions against diabetes-induced hepatic injury. These findings highlight the potential of combining Bifidobacterium bifidum supplementation with metformin as a promising probiotic-based therapeutic approach for managing diabetes-related liver complications. Future studies are warranted to confirm these results and to optimize the long-term efficacy of probiotic interventions in diabetes management.