Multi-omics reveals that polystyrene microplastic exposure induces bone loss in mice by disrupting intestinal glycine metabolism

Polystyrene microplastic exposure induced a pronounced bone-loss phenotype in C57BL/6 mice, characterized by reduced bone density and trabecular bone volume together with impaired osteogenic differentiation. To determine whether this skeletal toxicity was mediated by the gut microenvironment, we performed fecal microbiota transplantation and found that microbiota from microplastic-exposed donors was sufficient to recapitulate bone loss in recipient mice, supporting a causal role for microbiota alterations. Consistent with this mechanism, recipients exhibited compromised intestinal barrier integrity and heightened intestinal inflammation, alongside a dysbiotic microbial profile marked by depletion of beneficial taxa and enrichment of pro-inflammatory bacteria. Integrative multi-omics analyses further connected these gut changes to osteogenic dysfunction, revealing suppression of osteogenesis-related programs and inhibition of key signaling pathways, including PI3K-AKT and WNT/β-catenin signaling. Finally, metabolomic findings guided the selection of glycine for supplementation, which, when initiated concurrently with FMT, attenuated the development of bone loss in recipients receiving fecal microbiota from PS-MP-exposed donors.