Type 2 diabetes mellitus (T2DM) affects over 460 million individuals worldwide, of whom approximately 70% develop diabetic hepatopathy. Emerging evidence implicates gut microbiota dysbiosis as a central contributor to hepatic complications by disrupting the gut-liver axis. This study aimed to evaluate the hepatoprotective efficacy of Zingiber officinale (ginger) extract, alone and in combination with metformin, against diabetes-induced liver injury by modulating gut microbiota. Sixty male Wistar rats were randomly assigned to six experimental groups (n = 10 per group): control, ginger monotherapy, diabetic control, diabetic with ginger treatment, diabetic with metformin treatment, and diabetic with combination therapy. T2DM was induced using a high-fat diet (HFD) followed by low-dose streptozotocin (STZ) (30 mg/kg), and treatments were administered for 14 weeks. Comprehensive evaluations included metabolic profiling, liver function tests, antioxidant enzyme assays, histopathological examinations, and 16S rRNA-based analysis of gut microbiome. Diabetic rats exhibited severe gut dysbiosis characterized by 75% depletion of firmicutes and an 8-fold increase in proteobacteria. Ginger administration significantly restored microbial diversity, normalized the firmicutes/bacteroidetes ratio (F/B ratio), and markedly increased Akkermansia muciniphila abundance (from 0.2% to 2.1%). Furthermore, ginger treatment significantly improved insulin sensitivity (50% reduction in homeostatic model assessment of insulin resistance (HOMA-IR)), enhanced pancreatic β-cell function (95% recovery of HOMA-β), and normalized dyslipidemic profiles. Hepatic protection was associated with substantial restoration of antioxidant enzymes (78–85%) and attenuation of inflammatory responses. Notably, combination therapy with metformin yielded superior outcomes across all measured parameters, suggesting a synergistic interaction. These findings underscore the therapeutic potential of Z. officinale , particularly in combination with metformin, for mitigating diabetic hepatopathy by modulating the gut-liver axis, and support its translational relevance as a microbiome-targeted intervention in T2DM management.
Alaa T. Qumsani (Fri,) studied this question.