Peptidoglycan Derived From <i>Bifidobacterium animalis</i> KL101 Inhibits RANKL‐Induced Osteoclastogenesis Targeting Oxidative Stress and Autophagy Pathways

Postbiotics derived from probiotic components or metabolites have emerged as promising therapeutic agents for managing inflammation and oxidative stress–related diseases. The inhibitory effects of the peptidoglycan (PGN) fraction of Bifidobacterium animalis KL101 on receptor activator of nuclear factor–kappa B (NF‐κB) ligand (RANKL)–induced osteoclast differentiation were investigated in RAW264.7 macrophages. PGN (10 and 20 μg/mL) significantly reduced tartrate‐resistant acid phosphatase (TRAP) activity, suppressed nuclear factor of activated T‐cells, cytoplasmic 1 (NFATc1), and downregulated osteoclast‐specific genes such as matrix metalloproteinase‐9 (MMP‐9) and Cathepsin K (CtsK). Moreover, PGN decreased intracellular reactive oxygen species (ROS) levels and upregulated heme oxygenase–1 (HO‐1), mitigating ROS‐mediated signaling pathways such as the NF‐κB pathway. In addition, PGN also modulated autophagy, reducing the ratio of microtubule‐associated protein 1 light chain 3–II to LC3–I (LC3–II/LC3–I) and restoring p62/SQSTM1 (p62) levels, thereby impairing osteoclastogenesis. These findings highlight the dual role of PGN from B. animalis KL101 in inhibiting ROS and autophagy pathways critical to osteoclast differentiation and function. This study identifies the PGN of B. animalis KL101 as a promising postbiotic candidate for controlling osteoclast‐mediated bone degradation in disorders such as osteoporosis and periodontitis.