Type 2 diabetes mellitus (T2DM), the most prevalent form of diabetes, affects approximately 90% of individuals diagnosed with the condition [1]. This metabolic disorder is becoming increasingly prevalent worldwide and affects individuals across the age spectrum from childhood to senescence [2]. Characterized by impaired glucose tolerance, hyperglycemia, dyslipidemia, and systemic inflammation [3], T2DM frequently leads to severe complications including diabetic nephropathy, neuropathy, retinopathy, cardiovascular disease, and nonalcoholic fatty liver disease (NAFLD), collectively compromising patient outcomes and quality of life [2,4]. Consequently, identifying novel biomarkers and therapeutic strategies for T2DM management holds critical importance.

Sedentary behavior and poor dietary habits, particularly high-fat and high-calorie diets, have been identified as the primary contributors to the global diabetes epidemic [2]. Emerging evidence highlights a functional link between gut microbiota composition and T2DM pathogenesis, particularly in high-fat diet (HFD)-induced T2DM [5,6]. The gut microbiota, a diverse microbial community comprising trillions of microorganisms, plays a crucial role in preserving intestinal homeostasis and promoting systemic health. Previous reports have indicated that T2DM-associated gut microbiota dysbiosis is characterized by compositional alterations, including reduced diversity and microbial abundance [7,8]. The gut microbiota composition in T2DM patients exhibits marked dysbiosis, characterized by elevated levels of Firmicutes and Actinobacteria alongside reduced abundance of Bacteroidetes [9]. Additionally, the Bacteroides/Firmicutes ratio demonstrates a significant positive correlation with blood glucose level [10]. Furthermore, decreased α diversity within the gut microbiota is strongly associated with higher body mass index (BMI) in individuals with T2DM [10]. Emerging evidence collectively links gut microbiota imbalance to metabolic disruptions, including insulin resistance, oxidative stress, chronic inflammation, and intestinal barrier function, all of which may contribute to the pathophysiology of T2DM [11,12].

The dietary intake of nutrients and bioactive compounds plays a pivotal role in maintaining the balance between the gut microbiota and the host, primarily through the modulation of microbial composition and metabolic activity [13]. Prebiotic supplements are widely regarded as safe for consumption due to their selective utilization by beneficial microorganisms, demonstrating efficacy in restoring gut microbial homeostasis and ameliorating T2DM-related pathologies [14]. Clinical trials have confirmed that prebiotic supplementation enhances insulin sensitivity and reduces systemic inflammation in T2DM patients [15,16]. Inulin and fructo-oligosaccharides (FOS) are dietary fibers recognized for their prebiotic properties and potential health benefits. The distinct benefits of inulin and FOS in alleviating metabolic disorders through modulation of the gut microbiota have been widely reported [17,18]. Although inulin and FOS share similar structures, it is crucial to emphasize significant differences in their polymerization (DP). Notably, inulin typically exhibits a broader DP range (3–60), whereas FOS generally demonstrates lower molecular weights with DP values ranging from 3 to 10. Evidence has demonstrated that DP variations directly determine the biological specificity of polysaccharides [19]. In vitro research has established that such structural differences confer distinct prebiotic functionalities to inulin and FOS [20]. Nevertheless, comparative analyses evaluating the differential impacts of insulin and FOS on T2DM-associated metabolic parameters and microbial community dynamics remain insufficiently explored.

The effects of inulin and FOS on metabolic disorders in HFD-induced T2DM mice were systematically investigated in this study. A comparative analysis was conducted to evaluate the differential capacity of inulin and FOS to ameliorate metabolic dysregulation, including hyperlipidemia, insulin resistance, oxidative stress and systemic inflammation, while simultaneously assessing their regulatory effects on gut microbial community structure and compositional dynamics. This study aims to provide novel mechanistic insights for T2DM therapeutic strategies while establishing an evidence-based framework for optimizing prebiotic applications (specifically inulin and FOS) in chronic metabolic disease.