Dietary Fiber Intake Improves Osteoporosis Caused by Chronic Lead Exposure by Restoring the Gut–Bone Axis

<b>Background:</b> Lead (Pb), a pervasive environmental toxicant with specific toxicity to bone, has been recognized as a significant etiological factor in the pathogenesis of osteoporosis. While dietary fiber (DF) demonstrates anti-osteoporotic potential, its protective role against Pb-induced bone loss remains unexplored. <b>Methods:</b> This study analyzed the association between dietary fiber, blood lead, and osteoporosis based on the NHANES database, and validated it by constructing a lead exposed mouse model. Micro CT was used to evaluate bone microstructure, ELISA was used to detect bone markers, q-PCR/Western blot was used to measure intestinal tight junction protein, flow cytometry was used to analyze Treg cells in colon/bone tissue, GC-MS was used to detect short chain fatty acids, and 16S rRNA sequencing was used to analyze changes in gut microbiota. The regulatory mechanism of dietary fiber on bone metabolism and intestinal barrier in lead exposed mice was systematically evaluated. <b>Results:</b> Based on NHANES data analysis, it was found that dietary fiber can reduce the risk of osteoporosis in lead exposed populations. Animal experiments have shown that dietary fiber intervention significantly increases bone density, improves bone microstructure and metabolic indicators, repairs intestinal barrier damage caused by lead exposure, and regulates immune balance in lead exposed mice. At the same time, it promotes the generation of short chain fatty acids and the proliferation of beneficial gut microbiota. <b>Conclusions:</b> These findings indicate that DF mitigates Pb-induced osteoporosis through gut barrier restoration, SCFA-mediated immunomodulation, and microbiota-driven Treg cell expansion along the gut-bone axis.