Oral Propolis Nanoemulsions\nModulate Gut Microbiota\nto Balance Bone Remodeling for Enhanced Osteoporosis Therapy

The discovery of the bone–gut axis linking bone\nmetabolism\nto gut microbiota (GM) dysbiosis has revolutionized our understanding\nof managing degenerative skeletal diseases. Targeting GM regulation\nhas emerged as a promising approach to osteoporosis treatment. Herein,\nwe develop propolis nanoemulsions (PNEs) with enhanced gastrointestinal\nstability and oral bioavailability for GM-based osteoporosis therapy.\nOrally administered PNEs exhibit superior antiosteoporosis efficacy\nin an ovariectomized (OVX) mouse model by modulating the GM structure\nand metabolites and restoring the intestinal barrier function. Multiomics\nanalysis reveals that a reduction in <i>Streptococcus</i> abundance and an increase in the GM metabolite l-arginine\nare key factors in osteoporosis management. These changes suppress\nosteoclast activity and enhance osteoblast function, leading to balanced\nbone remodeling and, thus, significant antiosteoporotic effects via\nthe gut–bone axis. Our results deepen insights into the intricate\nrelationship between GM and bone remodeling, suggesting a promising\nstrategy that maintains the homeostasis of the GM structure and metabolite\nfor osteoporosis treatment.