A barrier-centered perspective on the gut-barrier-bone axis: a review of the core role of the intestinal barrier and related probiotics with nanocoatings.

Osteoporosis (OP) is a major public health problem characterized by reduced bone mass, deterioration of bone microarchitecture, and increased fracture risk. Growing evidence links the gut microbiota (GM) to bone remodeling, but the intestinal barrier is often treated as one component of microbiota-driven inflammation rather than as an interface that coordinates microbial, immune, endocrine, and nutritional signals. This review therefore adopts a barrier-centered perspective within the established gut-bone axis. We synthesize how epithelial, mucus, and immune barrier dysfunction may alter microbial products, immune-cell trafficking, gut-derived hormones, and nutrient handling, while distinguishing mechanistic evidence from association. Particular attention is given to Th17/Treg balance, macrophage responses, estrogen, serotonin, glucagon-like peptides, and mineral and vitamin absorption. We also critically evaluate nano-coated probiotics as a preclinical strategy to improve probiotic survival, mucosal retention, and barrier repair.This review adopts a barrier-centered perspective within the gut-bone axis and systematically summarizes the mechanisms through which the GM may influence the development and progression of OP via intestinal barrier dysfunction, with particular emphasis on immune dysregulation. Additionally, regarding novel intervention strategies for OP, this review specifically explores the technical advantages, mechanisms of action, and challenges in clinical translation of nano-coated probiotics. This review aims to provide a new theoretical framework and insights for research into the pathogenesis of OP, intervention strategies targeting the intestinal barrier, and clinical prevention and treatment.