Gut Microbiota And Short Chain Fatty Acids Influence Bone Health In Postmenopausal Osteoporosis

Postmenopausal osteoporosis (PMOP) is framed arsenic a systemic bony illness driven by estrogen withdrawal, but emerging grounds positions gut dysbiosis and its fermentation products—short-chain fatty acids (SCFAs)—as arsenic influential regulators of skeletal fate. Estrogen nonaccomplishment elevates gut permeability, allowing lipopolysaccharide and pro-inflammatory T cells to postulation from intestine to bony marrow, tipping nan Th17/Treg equilibrium toward osteoclast-promoting cytokines specified arsenic IL-17, TNF-α and RANKL. Germ-free aliases T-cell-depleted mice do not suffer bony aft ovariectomy, underscoring nan microbiota-immune axis arsenic a mechanistic core.

Cross-sectional profiling reveals PMOP cohorts harbor reduced alpha-diversity, a Firmicutes-enriched/Bacteroidetes-depleted signature, and little butyrate- and propionate-producing taxa specified arsenic Butyricicoccus, Fusicatenibacter and Prevotella histicola. Conversely, pathobionts including Klebsiella, Escherichia and Clostridium are expanded; their endotoxin and AKT2 signaling amplify M1 macrophage polarization and systemic inflammation. These compositional shifts correlate pinch circulating C-telopeptide, osteocalcin and hep BMD, suggesting GM signatures whitethorn service arsenic biomarkers aliases therapeutic targets.

Fecal microbiota transplantation from patient donors into ovariectomized mice restores intestinal obstruction integrity, rebalances Th17/Treg ratios successful some gut and bony marrow, and prevents trabecular bony loss. Probiotic supplementation pinch Lactobacillus rhamnosus GG, L. reuteri aliases Bifidobacterium longum recapitulates these benefits: tight-junction proteins ZO-1 and occludin rise, LPS leakage falls, and Treg-derived IL-10 and TGF-β suppress osteoclastogenesis while enhancing osteoprotegerin expression. Lactic acid, a metabolite of Lactobacillus, further induces histone lactylation successful bone-marrow mesenchymal stem cells, steering committedness toward osteoblast differentiation.

SCFAs look arsenic cardinal molecular translators of microbial influence. Acetate, propionate and butyrate—generated via fermentation of dietary fiber by Firmicutes and Bacteroidetes—signal done GPCRs (GPR41, GPR43, GPR109A) and enactment arsenic histone-deacetylase inhibitors. In nan gut, they acidify nan lumen, summation calcium solubility and transporter expression, and reenforce epithelial obstruction integrity.

Systemically, these metabolites skew CD4+ T-cell destiny toward Foxp3+ Tregs while restraining Th17 differentiation, thereby dampening RANKL-mediated osteoclast activation. In bone-marrow cultures, butyrate suppresses NF-κB and p38 MAPK signaling, down-regulates NFATc1, c-Fos and TRAP, and reduces mature osteoclast numbers. Propionate and butyrate displacement early osteoclast precursors from oxidative phosphorylation to glycolysis, creating metabolic accent incompatible pinch differentiation.
Osteoblast lineage cells respond favorably to SCFAs: butyrate dose-dependently increases bone-sialoprotein, osteopontin and osteoprotegerin transcription, enhances mineralized nodule formation, and amplifies Wnt10b look successful a Treg-dependent mode erstwhile mixed pinch intermittent parathyroid hormone. Conversely, high-dose butyrate exerts cytostatic effects, illustrating concentration-dependent pleiotropy.

Clinical and pre-clinical grounds converge connected dietary aliases microbial interventions that elevate SCFAs arsenic adjunctive PMOP therapies. High-fiber diets summation acetate and butyrate, forestall ovariectomy-induced bony loss, and synergize pinch calcium and vitamin D. A 12-month probiotic proceedings reported humble lumbar-spine BMD gains, while multi-strain formulations reduced bone-turnover markers without changing BMD, highlighting nan request for longer follow-up. Outstanding questions see optimal SCFA type ratios, dose thresholds, and interactions pinch anti-resorptives aliases anabolic drugs. Multi-omics integration—metagenomics, metabolomics and immune-phenotyping—should guideline personalized microbiome-based strategies that safely heighten skeletal wellness beyond existent pharmacologic limits.