Abstract
BACKGROUND: Male reproductive health is intricately linked to dietary components and gut microbiota balance. Osteopontin (OPN) deficiency and gut dysbiosis are associated with impaired spermatogenesis, yet the synergistic effects of probiotics and OPN remain unexplored. RESULTS: In OPN-deficient mice, combined intervention with Bifidobacterium longum subsp. infantis B8762 and OPN increased gut microbiota alpha diversity and upregulated key reproductive genes (Etv4, Adamts16, Prok2, Gpr55, Rad54b). Testicular histology revealed restored spermatogenic cell density and seminiferous tubule integrity. CONCLUSION: This study demonstrates that co-administration of B8762 and OPN alleviates reproductive dysfunction via gut microbiota modulation and testicular gene regulation, offering a novel nutritional strategy for male fertility enhancement. © 2025 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.