Maintaining gut microbiota micro-environment homeostasis via silver-nanocubes for ameliorating estrogen deficiency-induced osteoporosis

Abstract

Osteoporosis (OP) is a prevalent bone disorder characterized by decreased bone density and increased fracture risk, particularly affecting postmenopausal women. Recent research has revealed that gut microbiota plays a crucial role in OP progression, which emphasizes the concept of the “gut-bone axis.” Dysbiosis, or an imbalance in gut microbiota, contributes to bone loss by promoting systemic inflammation, impairing nutrient absorption, and altering immune responses. Silver nanocubes (AgNC), due to their anti-inflammatory, anti-angiogenic, and gut microbiota-regulating abilities, show promising therapeutic effects on inflammatory conditions such as rheumatoid arthritis (RA). However, the protective effects of AgNC on the progression of OP remain unclear. Here, we found that AgNC alleviated OP progression by altering the structure and composition of gut microbiota, particularly by increasing the abundance of beneficial bacteria, notably the genera Lactobacillus and Bifidobacterium. These probiotics play a crucial role in maintaining bone health by enhancing gut integrity, reducing inflammation, and promoting immune homeostasis. Specifically, AgNC treatment improved gut barrier function by upregulating tight junction proteins such as Claudin-1 and ZO-1, thereby reducing the translocation of pro-inflammatory molecules. Furthermore, AgNC modulated the immune environment by increasing the population of Treg cells and decreasing Th17 cells in the bone marrow, thus maintaining the Th17/Treg balance. This shift leaded to reduced release of inflammatory cytokines, including CXCL1, IL-23p19, IL-1β, and MCP-1, contributing to the preservation of bone mass. Collectively, these findings suggested that AgNC mitigated OP in a gut microbiota-dependent manner, offering a novel approach for OP treatment by targeting the gut-bone axis.