The attempt microbiota and short chain fatty acids influence bone health in postmenopausal osteoporosis

Postmenopausic osteoporosis (PMOP) is framed as a systemic bone disease driven by estrogen withdrawal, but emerging evidence positions intestinal dysbiosis and its fermentation products: chain chain fatty acids (SCFA), as equally influential regulators of skeletal destination. The loss of estrogen raises intestinal permeability, which allows lipopolysaccharide and pro-inflammatory T cells of the intestine trafficking to the bone marrow, tilting the th17/treg balance towards the cytokines promoted by osteoclasts, such as IL-17, TNF-α and Randl. Germs -free mice with T cells do not lose bone after ovariectomy, underlining the immune microbiota axis as a mechanistic nucleus.

The transversal profile reveals that PMOP cohorts house a reduced alpha-docal reduction, a firm enriched by firmicutes/bacteroides, and the lowest taxons of butyrate and propionate such as butyricicoccus, fusicatenibacter and prevotella histticola. On the contrary, Pathobions expand, including Klebsiella, Escherichia and Clostridium; Its endotoxin and AKT2 signage amplifies the polarization of M1 macrophages and systemic inflammation. These compositional changes correlate with the circulating tlopeptide C, osteocalcine and hip dmo, suggesting that GM firms can serve as biomarkers or therapeutic objectives.

The fecal microbiota transplant of healthy donors in ovariectomized mice restores the integrity of the intestinal barrier, recipes Th17/treg relations in the intestinal marrow and bone marrow, and prevents trabecular bone loss. Probiotic supplementation with lactobacillus rhamnosus gg, L. reuteri or bifidobacterium longum recapitulates these benefits: narrow union proteins zo-1 and the ocludin increases, the leaks of LPs fall and the expression of ITL-10 derived from TREG and TGF-β suppresses the ostoclastogenesis of the oste. of TGF-β. Lactic acid, a metabolite of Lactobacillus, further induces histone lactilation in the mesenquimal stem cells of the bone current, the direction of direction towards the differentiation of osteoblasts.

The scfa emerge as central molecular translators of microbial influence. Acetate, Propionate and Butirate, generated by fermentation of dietary fiber by firmicutes and bacteroides, firm through GPCR (GPR41, GPR43, GPR109A) and act as histone-disacilase inhibitors. In the intestine, they acidify the light, increase calcium solubility and transporter expression, and reinforce the integrity of the epithelial barrier.

Systemically, these metabolites skewed the destination of CD4+ cells towards FOXP3+ TREGS while restricting the differentiation of TH17, thus cushioning the activation of osteoclasts mediated by Rankl. In bone matter crops, butyrate suppresses the signage of NF-κB and P38 Mapk, regulates NFATC1, C-Fos and Trap, and reduces mature osteoclast numbers. Propionate and butyrate change the precursors of early osteoclasts of oxidative phosphorylation to glycolysis, creating metabolic stress incompatible with differentiation.

Osteoblast lineage cells respond favorably to SCFA: the transcription of the butirate dose increases depending bonely, the transcription of osteopontin and osteoprotegerine, improves the formation of mineralized nodules, and amplifies the WNT10B expression in a TREG dependent manner when combined with the intermittent parathyroid hormone. On the contrary, high butyrate exerts cytostatic effects, illustrating the concentration -dependent pleiotropy.

The clinical and preclinical evidence converges in dietary or microbial interventions that raise scfa as attached therapies of PMOP. High fiber diets increase acetate and butyrate, prevent bone loss induced by ovariectomy and are synerus with calcium and vitamin D. A 12 -month probiotic test report longer tracking. Outstanding questions include optimal relationships of scfa species, dose thresholds and interactions with anti-residents or anabolic drugs. Multiple multiple integration (metagenomic, metabolomic and immune phenotyped) must guide personalized strategies based on microbiomas that safely improve skeletal health beyond current pharmacological limits.