Black-Bean-Derived Oligopeptides Ameliorate Osteoporosis via Modulation of Gut Microbiota and Glutamate Metabolism

Osteoporosis is a systemic skeletal disease caused by disrupted bone homeostasis. Black-bean-derived oligopeptides have shown promise as natural osteogenic candidates, yet their roles in mitigating osteoporosis based on gut microecology modulation remain poorly understood. In this study, black-bean-hydrolyzed peptides (<1 kDa), KIGT, and KGVG significantly improved bone mass and microarchitecture in ovariectomy (OVX) mice, primarily owing to osteoanabolic activities. All three oligopeptides ameliorated gut microbiota dysbiosis by increasing the abundance of <i>Bacteroides</i>, <i>Bilophila</i>, <i>Bifidobacterium</i>, and <i>Lactobacillus</i>, which were highly associated with the intestinal levels of glutamic acid and α-ketoglutaric acid (α-KG). Notably, α-KG exhibited the strongest positive correlation with bone mass in OVX mice. <i>In vitro</i> assays confirmed that α-KG stimulated bone formation by activating Wnt/β-catenin signaling. This study highlights the antiosteoporosis effects of black-bean oligopeptides via regulation of the gut microbiota and metabolites, providing novel mechanistic insights into peptide-based therapies for bone-related disorders.