Peng Qi ¹ Hao Liu ¹ Zixuan Zhang ¹ Yuan Cheng ¹ Jilong Ma ¹ Kangwei Wan ¹ Xingwen Xie ^1,2*

• ¹ Gansu University of Chinese Medicine, Lanzhou, China
• ² Affiliated Hospital of Gansu University of Traditional Chinese Medicine, Lanzhou, Gansu Province, China

Postmenopausal osteoporosis (PMOP) is a metabolic bone disease driven by estrogen deficiency, primarily manifesting as reduced bone mass and heightened fracture risk. Its development is intricately linked to the balance between Th17 and Treg cells. Recent studies have highlighted the significant role of gut homeostasis in PMOP. The gut microbiota profoundly impacts bone health by modulating the host's immune system, metabolic pathways, and endocrine functions. In particular, the regulation of Th17 and Treg cell balance by gut homeostasis plays a pivotal role in the onset and progression of PMOP. Th17 cells secrete proinflammatory cytokines that stimulate osteoclast activity, accelerating bone resorption, while Treg cells counteract this process through anti-inflammatory mechanisms, preserving bone mass. The gut microbiota and its metabolites can influence Th17/Treg equilibrium, thereby modulating bone metabolism. Furthermore, the integrity of the gut barrier is critical for systemic immune stability, and its disruption can lead to immune dysregulation and metabolic imbalances. Thus, targeting gut homeostasis to restore Th17/Treg balance offers a novel therapeutic avenue for the prevention and treatment of PMOP. that drives the differentiation of helper T cells 17 (Th17) and regulatory T cells (Treg) (10). Alterations in the gut microbiota are closely associated with changes in bone mass, particularly through their role in bone immunology and the gut-bone axis (11,12). Previous studies have investigated the role of the gut microbiota in PMOP (13). Thus, elucidating the mechanisms by which gut homeostasis regulates the Th17/Treg balance could provide valuable insights into the pathogenesis of PMOP and inform the development of novel therapeutic strategies.PMOP is primarily caused by estrogen deficiency, which leads to decreased bone mass, deterioration of microarchitecture, and impaired bone metabolism. A hallmark pathological feature of PMOP is the imbalance between bone resorption and formation, with accelerated resorption outpacing bone formation ( 14). Recent advances in osteoimmunology have revealed that estrogen deficiency induces a chronic low-grade inflammatory state, significantly contributing to disease progression. This inflammatory response is mediated through various immune pathways, driving the pathological mechanisms underlying PMOP. System is shown in Fig. 1