Strontium ameliorates tibial dyschondroplasia in broilers through gut microbiota-mediated retinoic acid metabolism

Tibial dyschondroplasia (TD) is a prevalent skeletal disorder in fast-growing broilers that impairs animal welfare and production efficiency. Although strontium (Sr) is known to support bone-strengthening properties, its protective mechanisms against TD, particularly those involving the gut‒bone axis, remain unclear. This study showed that dietary Sr supplementation (200 mg/kg) significantly improved growth performance, restored the tibial microstructure, corrected plasma calcium/phosphorus imbalances, enhanced chondrocyte alignment, increased the osteoblast density, increased the bone mineral density, and improved vascularization in the proximal tibial growth plate in TD broilers. Moreover, the Sr intervention upregulated the bone morphogenetic protein-mediated osteogenic pathway while suppressing RANKL activity and promoted angiogenesis by activating the VEGFA and PI3K/AKT/eNOS signaling pathways, thereby restoring bone remodeling. Interestingly, Sr remodeled the gut microbiota of TD broilers, enriching the beneficial species Pediococcus pentosaceus and reducing the abundance of Levilactobacillus brevis, changes that were correlated with the level of the osteotoxic metabolite 9-cis-retinoic acid (9-cis-RA). Furthermore, exogenous retinoic acid (RA) administration induced TD-like damage, whereas Sr cotreatment mitigated the RA-induced tibial impairment, vascular defects, and dysregulation of the PI3K/AKT/eNOS pathway. Collectively, these results demonstrated that Sr alleviated TD by modulating the gut microbiota to inhibit 9-cis-RA accumulation, thereby normalizing retinoic acid metabolism, promoting vascularization and enhancing osteogenesis; these findings provide novel insights for preventing leg disorders in poultry.