Enhanced Osteoporosis Treatment via Nano Drug Coating Encapsulating <i>Lactobacillus rhamnosus</i> GG

Osteoporosis is the most common systemic skeletal disorder, particularly associated with aging and postmenopausal women. With the growing knowledge about the gut-bone axis, the therapeutic strategies for osteoporosis have been shifted toward regulating gut microbiota to promote positive bone metabolism. Although<i>Lactobacillus rhamnosus</i> GG (LGG) is widely reported to positively regulate bone metabolism by restoring the dysbiotic microbiome, oral administration is associated with sensitivity to gastric fluid and low bioavailability. Other studies also demonstrated that bisphosphonates ameliorate osteoporosis by directly regulating bone metabolism, especially inhibiting osteoclast activity. However, the side effects caused by bisphosphonate treatment still represent a significant problem. In this study, we assembled alendronate, a clinically used bisphosphonate, with DSPE-phospholipid nanoencapsulation and LGG (ADB), to protect LGG from the acidic environment of the stomach, while simultaneously reducing the gastrointestinal side effects associated with the oral administration of alendronate. We further investigated the potential of these DSPE-phospholipid nanoencapsulated bacteria ADB to repair osteoporotic bone deterioration, and their ability to regulate gut microbiota <i>in vivo</i>, which is strongly associated with the intrinsic environment. Compared with the same dosage of LGG and alendronate alone, ADB positively regulated bone metabolism, and osteoporosis was significantly revised in ovariectomized mice models.