Gut microbiota-metabolome remodeling associated with low bone mass: an integrated multi-omics study in fracture patients.

Background: The gut microbiota is increasingly implicated in the pathogenesis of osteoporosis, but its role in the specific context of fracture patients remains poorly defined. High-resolution multi-omics studies are needed to elucidate the complex interplay between microbes, their metabolites, and bone health. This study aimed to characterize the gut microbial and fecal metabolic signatures associated with low bone mass in fracture patients. Methods: We conducted a cross-sectional study of 51 fracture patients, stratified by bone mineral density into Normal, Osteopenia, and Osteoporosis groups. For key analyses, the latter two groups were combined into a Low Bone Mass (LBM) group. We performed shotgun metagenomic sequencing and untargeted liquid chromatography-mass spectrometry metabolomics on fecal samples. An integrated bioinformatics and statistical analysis were used to identify differential taxa and metabolites, construct correlation networks, and build diagnostic biomarker models. Results: Patients with LBM exhibited a distinct gut microbial and metabolic profile compared to controls. A notable finding was the unexpected enrichment of Conclusion: Our findings reveal a significant remodeling of the gut microbiota-metabolome axis in fracture patients with low bone mass, highlighting a context-dependent, potentially pathological role for the typically beneficial species