Impairments of the extracellular matrix are the direct or indirect cause of most chronic diseases, including Alzheimer’s disease, cardiovascular disease, cancer, and bone fragility. Age-related reductions in bone mineral density (BMD) are a major contributor to bone fragility, but age-related impairment of the bone extracellular matrix has an even greater effect on whole bone strength and resistance to clinical fractures. Impairments to the bone extracellular matrix are thought to be irreversible and therefore not targeted by existing therapeutics. Here, I discuss recent preclinical studies demonstrating that the gut microbiome can modulate the bone extracellular matrix in the adult skeleton. Specifically, we find that changes in the composition of the gut microbiome can lead to impairment or improvement of bone matrix strength or toughness – an effect that is not limited to matrix formed after the change in the gut microbiome and therefore does not appear to be related to osteoclast/osteoblast-mediated bone modeling and remodeling. Surprisingly, microbiome-induced changes in bone matrix are associated with the same transcriptional changes in bone observed in age-related impairment of bone matrix and can be induced by transfer of the gut microbiota from an older animal into a younger animal. I discuss investigations into the molecular signals and responsive cell populations that enable the gut microbiome to alter the composition and function of the bone extracellular matrix. This work and that from other groups suggest the feasibility of interventions that can enhance bone extracellular matrix, thereby reducing fracture risk below what is currently possible with therapeutics that focus on increasing bone mineral density.