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Intestinal-Bone Axis Mediated by Bifidobacterium: Mechanistic Analysis and Therapeutic Potential in Osteoporosis

Li F, Zhang H, Zhang B, Xie X, Li N

Microorganisms, 2026

Abstract

Osteoporosis is one of the most prevalent metabolic bone diseases worldwide, and current pharmacological options are limited by adverse effects and are poorly suited to long-term use, underscoring the need for novel therapeutic targets. Bifidobacterium, one of the most representative beneficial bacterial genera in the human gut, has been linked to bone mineral density, and supplementation with specific strains improves bone metabolic parameters in animal models of osteoporosis. This narrative review examines the molecular mechanisms through which Bifidobacterium may protect bone via the gut-bone axis, encompassing four interconnected dimensions: reinforcement of the intestinal barrier, modulation of the immune network, remodeling of the gut microbiota, and production of bone-protective metabolites. The review makes three principal contributions. First, it establishes a four-tier mechanistic framework of Bifidobacterium-mediated regulation of osteoporosis in which the evidence is stratified into three categories-direct evidence from Bifidobacterium-specific studies, indirect evidence from other probiotics, and general mechanisms of gut microbiota-regulated bone metabolism-thereby strengthening the rigor of each argument and explicitly distinguishing evidence derived from Bifidobacterium-specific studies from that based on other probiotics or general gut-microbiota mechanisms throughout the review. Second, it systematically compares the osteoprotective efficacy of different…

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