The “gut-immune-bone axis”: quantitative MRI reveals the microbial-immune-bone metabolic interplay in osteoporosis

Osteoporosis is a systemic skeletal disorder, whose pathogenesis is related to abnormalities in bone metabolism, as well as gut microbiota and immune system dysregulations. This structured narrative review synthesizes recent evidence on the “gut-immune-bone axis” in osteoporosis, with emphasis on studies published from 2020 to 2025 and selected later studies incorporated during manuscript revision when directly relevant. This article first outlines the direct and indirect regulatory roles of gut microbiota and its products (short-chain fatty acids, tryptophan catabolites, etc.) in bone metabolism. It then focuses on immune cells that participate in bone remodeling, including the Th17/Treg balance, B cells, and macrophages, and their interactions with the gut microbiota. The review further discusses recent developments in quantitative magnetic resonance imaging for quantifying bone microarchitecture, marrow composition, and metabolic status and considers how these measures may serve as downstream phenotyping tools in studies of the gut–immune–bone axis. Finally, an integrative model of the microbial-immune-bone metabolic network is proposed and translational strategies, including microbiome-directed interventions, immunomodulatory therapies, and multi-omics approaches, are critically discussed.