Effects of <i>Lactiplantibacillus plantarum</i> W1, inulin, and their combination against dexamethasone-induced osteoporosis via modulation of microRNA and gut microbiome

Glucocorticoid-Induced Osteoporosis (GIO) is a common secondary form of osteoporosis characterized by rapid bone loss. While probiotics and prebiotics modulate the gut microbiota and influence host metabolism, their specific impact on GIO and associated molecular mechanisms remain unexplored. Lactiplantibacillus plantarum W1 (LpW1) represents a promising probiotic with reported protective effect against different diseases. In this study, seventy Wistar rats were assigned to seven groups (n=10) as follows: Control (CON), L. plantarum W1 alone (Lp), inulin alone (In), dexamethasone alone (DX), (DX+Lp), (DX+In), and (DX+Lp+In). Treatments lasted for 12 weeks. Bone morphology, serum calcium, phosphorus, alkaline phosphatase, bone histopathology, expression of miRNA-29b and miRNA-133, and gut microbiota diversity were assessed. The co-treatment groups (DX+Lp, DX+In, DX+Lp+In) showed improved bone health, reduced alkaline phosphatase activity, and enhanced serum mineral levels. Inulin significantly reduced miRNA-29b and miRNA-133 expression compared to the DX group. The Lp, In, and DX+Lp+In groups showed improved gut microbial profiles with enhanced alpha and beta diversity, compared to DX group. We conclude that inulin, LpW1, and their combination mitigated the skeletal abnormalities induced by DX treatment. Remarkably, Inulin alone demonstrated strong protective effects, and the synbiotic formulation reduced DX-induced osteoporosis.