GUT MICROBIOTA AS A MODULATOR OF BONE REMODELING: MECHANISTIC INSIGHTS AND THERAPEUTIC IMPLICATIONS IN OSTEOPOROSIS

Resumo

Introduction: Osteoporosis (OP) is a multifactorial metabolic disease characterized by reduced bone mineral density (BMD) and impaired bone microarchitect ure, leading to increased fracture risk. Recent evidence supports the gut microbiota (GM) as a central regulator of bone homeostasis through immune, endocrine, and metabolic pathways, forming the gut -bone axis. Dysbiosis has been associated with systemic i nflammation, altered intestinal permeability, impaired nutrient absorption, and hormonal dysregulation, all contributing to enhanced osteoclastogenesis and bone loss. Objective: To analyze the mechanisms linking gut microbiota to bone remodeling and to evaluate the therapeutic potential of microbiota modulation in osteoporosis. Materials and Methods: A narrative review was conducted using PubMed, prioritizing recent studies (2020-2026) while including foundational evidence without temporal restriction. The search strategy combined descriptors such as “gut microbiota,” “osteoporosis,” “bone remodeling,” “probiotics,” and “short- chain fatty acids” using Boolean operators. Experimental, clinical, and translational studies addressing immunological, endocrine, me tabolic mechanisms and microbiota -targeted therapies were included. Results: The gut microbiota modulates bone remodeling through interconnected pathways. Immunologically, dysbiosis promotes pro-osteoclastogenic signaling via increased Th17 cells and infla mmatory cytokines (e.g., TNF -α, IL -17), whereas microbial metabolites such as short-chain fatty acids (SCFAs) enhance regulatory T cells and suppress osteoclast differentiation. Endocrine interactions involve modulation of estrogen metabolism, the GH/IGF -1 axis, parathyroid hormone (PTH), and gut -derived serotonin, highlighting the relevance of the enteroendocrine-bone axis . Metabolically, microbiota improves calcium bioavailability and regulates bile acid signaling pathways, including TGR5 - mediated effects on bone preservation. Experimental evidence from germ - free and antibiotic -treated models demonstrates significant alterations in bone mass and turnover following microbiota disruption, while probiotic interventions (e.g., Lactobacillus and Lacticaseibacillus strains) have shown anti-inflammatory and bone-protective effects in animal models and emerging clinical studies. Meta -analytical data suggest that probiotic supplementation may improve bone turnover markers in middle -aged and elderly populations, a lthough heterogeneity remains. Conclusion: Gut microbiota modulation represents a promising adjunctive strategy in osteoporosis management. Current evidence suggests that microbiota- targeted interventions may be associated with improvements in bone densit y and remodeling markers; however, these effects vary according to experimental models, studied populations, and types of intervention. Further large -scale, well -controlled clinical trials are required to establish causal relationships and therapeutic applicability.