Osteoporosis (OP) is a chronic metabolic bone disease characterized by diminished bone mass, decreased bone strength, deterioration of bone microarchitecture, and increased bone fragility with fracture risk. The aging population has made OP a public health problem that has serious effects on individuals, families, and society as a whole. It is urgent that new strategies that are safe, effective, and inexpensive for the treatment of OP should be developed. Increasing evidence has suggested that the gut microbiota (GM) is inextricably linked to bone homeostasis through cross-talk between host and microbiota. During the development of OP, GM perturbations can initiate and reinforce the disruption of bone remodeling balance. In this review, we first review the current knowledge of how the GM affects bone metabolism, and conclude that GM changes bone metabolism and participates in the formation of OP by affecting intestinal barrier, host metabolites, immune system and endocrine system. Then, we discuss that probiotics are expected to be a potential oral therapeutic strategy for OP, but there are limitations. Furthermore, we discuss how bioactive functional materials for providing probiotics to the gut can be constructed based on the chemical barrier, biological barrier, immune barrier, and mechanical barrier in the gut. This review is anticipated to stimulate further innovative thinking focusing on the intestinal barrier as a key target for delivery of probiotics and treatment of OP.
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