Microbiota diversity and its influence on diabetic osteoporosis development

Diabetic osteoporosis represents a form of secondary osteoporosis whereby diabetes, particularly through chronic hyperglycemia, compromises bone quality and elevates fracture risk. Recent studies using type II diabetes mellitus (T2DM) rat models induced by a high-fat diet (HFD) and low-dose streptozotocin (STZ) have revealed both gut microbiota dysbiosis and osteoporotic bone changes. However, the mechanisms by which the gut microbiota contributes to diabetic osteoporosis remain poorly understood. This study aimed to elucidate the underlying mechanisms of diabetic osteoporosis through microbiome profiling and pathway enrichment analysis. A male T2DM rat model was established via HFD feeding and STZ injection. Bone structural integrity was assessed using micro-computed tomography, while gut microbiota composition was analyzed via 16 S rRNA gene pyrosequencing and subsequent bioinformatic processing. The results showed that T2DM rats exhibited significantly elevated levels of proinflammatory cytokines, which were negatively correlated with bone density and bone turnover markers. Microbiota diversity analysis revealed a decrease in beneficial bacterial taxa, including Lactobacillus, Romboutsia, Turicibacter, and Clostridia UCG-014, alongside an increase in potentially pathogenic Enterococcus, despite a modest increase in other beneficial genera such as Parabacteroidetes, Intestinomonas, and Faecalibaculum. Functional enrichment analysis indicated impaired short-chain fatty acid (SCFA) metabolism, specifically reduced propanoate and butanoate pathway, and enhanced tryptophan metabolism, both of which were associated with decreased bone mass. These findings suggest that microbiota-driven alterations in SCFA production contribute to systemic inflammation and bone loss. Identification of key microbial metabolites and pathways may guide the development of microbiome-targeted therapies to improve metabolic and skeletal health in diabetic populations.