Orally administered degradable nanoarmor-assisted probiotics for remodeling the gut microenvironment and treating osteoporosis

Improving the intestinal microenvironment and regulating the intestinal flora are highly important in the treatment of osteoporosis. Although previous studies have shown that oral probiotics can prevent or reverse bone loss, their survival rate and therapeutic effect are greatly reduced when they pass through the gastrointestinal chemical microenvironment, which limits their clinical application. Therefore, improving their survival rate and therapeutic effect is crucial. To address this issue, we formed a metal‒phenolic network (L@Q-Ca) on the surface of Lactobacillus rhamnosus (LR) by combining quercetin and calcium metal ions to enhance its therapeutic effect. To enable the LR to pass successfully pass the gastrointestinal chemical environment, dopamine was polymerized on the surface of the probiotics, forming a dense protective layer (L@Q-Ca/PDA). Probiotics with the L@Q-Ca/PDA coating significantly outperformed traditional uncoated probiotics in terms of both their survival rate in the gastrointestinal tract and their therapeutic effect on osteoporosis. In the intestinal microenvironment, the composite material can effectively counteract intestinal inflammation, oxidative stress, barrier damage, and microenvironmental disorders. The alleviation of systemic inflammation restores the balance of osteoblast and osteoclast activity. The increased absorption of quercetin and short-chain fatty acids in the intestine can further improve the bone microenvironment. This oral probiotic reinforcement strategy is not only safe, reliable, and efficient, but also potentially amenable to an extremely broad range of applications for the clinical transformation of probiotics in the field of osteoporosis treatment.