Limosilactobacillus fermentum CCFM1126 attenuates osteoporosis by modulating the gut microbiota composition and fecal metabolites: A randomized, double-blind, placebo-controlled clinical trial

Osteoporosis (OP) is a common systemic metabolic bone disorder characterized by reduced bone mass and deteriorated bone microarchitecture. Limosilactobacillus fermentum CCFM1126 has previously been shown to mitigate intestinal barrier dysfunction and modulate bone metabolism, thereby attenuating bone loss in OP rat models. To further evaluate its clinical efficacy, a double-blind, randomized, placebo-controlled trial was conducted. Additionally, the optimal intervention dose and potential bioactive components were investigated using ovariectomized (OVX) rat models and MC3T3-E1 pre-osteoblast cell assays. In the clinical trial, CCFM1126 supplementation significantly increased bone mineral density (BMD), elevated serum calcium and 25-hydroxyvitamin D levels, and reshaped gut microbiota composition by reducing the relative abundances of Paraprevotella, Marvinbryantia, Ruminococcus 1, and Granulicatella. In OVX rats, a dose of 10⁷ CFU/mL exerted minimal effects on bone morphology and metabolism, whereas doses ≥ 10⁸ CFU/mL led to significant improvements in bone structure and systemic metabolic indices, accompanied by favorable modulation of the gut microbial profile. The most pronounced effects were observed at 10⁹ CFU/mL. In MC3T3-E1 pre-osteoblasts, metabolites derived from CCFM1126 enhanced cell viability and upregulated the expression of key osteogenic genes. Among these, choline was identified as a potential bioactive compound contributing to the anti-osteoporotic effects of CCFM1126.