Regulation of gut microbial dysbiosis and inflammatory microenvironment by GQD-derived nanoparticles for the treatment of colitis-associated osteoporosis

Traditional Chinese Medicine (TCM) formula derived nanoparticles (NPs) have been widely reported to exert therapeutic effects in various diseases; however, their application in disorders involving the gut-bone axis remains largely unexplored. Gegen Qinlian Decoction (GQD), a classical formula, is widely used for the treatment of colitis. Given that persistent intestinal inflammation and gut microbiota dysbiosis can contribute to osteoporosis as an extraintestinal complication, the present study aimed to isolate nanoparticles from GQD and determine whether these GQD derived nanoparticles (GQD_NPs) could alleviate chronic colitis induced bone loss. The NPs successfully isolated from GQD markedly ameliorated gut microbial dysbiosis, as evidenced by a reduction in the pathogenic Escherichia-Shigella and an increase in the beneficial Lactobacillus . Meanwhile, the levels of amino acids, including arginine, histidine, and leucine, as well as short-chain fatty acids such as acetic acid, propionic acid, and butyric acid, were significantly restored. These changes were accompanied by a pronounced alleviation of chronic colitis symptoms, including reduced expression of the pro-inflammatory cytokines IL-1β and TNF-α, increased expression of the anti-inflammatory cytokine IL-10, and recovery of intestinal immune and epithelial barriers. Notably, GQD_NPs also restored intestinal microbial and metabolic homeostasis in chronic colitis, thereby promoting favorable bone microstructural remodeling. These findings demonstrate that GQD_NPs exert protective effects against chronic colitis-associated bone loss by rebalancing the microbiota-bone axis, highlighting their therapeutic potential for the treatment of colitis and its related osteoporosis.