Combined exposure to microplastics and tetracycline leads to impaired skeletal development in young mice by the microbiota gut bone axis

Microplastics (MPs) and tetracycline (TCs) are widespread environmental pollutants, yet the impact of their co-exposure on children's skeletal development remains unclear. In this study, we constructed a young mouse model exposed to MPs and TCs both individually and in combination over 8 weeks to investigate the potential mechanisms of bone damage. We found that co-exposure significantly exacerbated colonic damage, inflammation, and gut barrier dysfunction compared to individual exposures. Critically, 16S rRNA sequencing revealed that co-exposure induced profound gut microbiota dysbiosis, characterized by a decreased Firmicutes/Bacteroidetes ratio, a reduction in beneficial genera, and an enrichment of pro-inflammatory genera. This was accompanied by increased systemic inflammation and elevated serum LPS. Subsequently, these disruptions inhibited the Wnt/β-catenin signaling pathway in bone, associated with impaired chondrocyte proliferation and differentiation, increased apoptosis, and ultimately suppression of endochondral ossification. Our results demonstrate that co-exposure to MPs and TCs disrupts the microbiota-gut-bone axis, resulting in delayed longitudinal bone growth and reduced bone density. Notably, this study is the first to confirm this phenomenon in mammals, while also highlighting the novel mechanistic link between gut microbiota dysbiosis and pollutant-induced skeletal impairments.