Lactobacillus plantarum attenuates glucocorticoid-induced osteoporosis by altering the composition of rat gut microbiota and serum metabolic profile

Abstract

IntroductionOsteoporosis, one of the most common non-communicable human diseases worldwide, is one of the most prevalent disease of the adult skeleton. Glucocorticoid-induced osteoporosis(GIOP) is the foremost form of secondary osteoporosis, extensively researched due to its prevalence.Probiotics constitute a primary bioactive component within numerous foods, offering promise as a potential biological intervention for preventing and treating osteoporosis. This study aimed to evaluate the beneficial effects of the probiotic Lactobacillus plantarum on bone health and its underlying mechanisms in a rat model of glucocorticoid dexamethasone-induced osteoporosis, using the osteoporosis treatment drug alendronate as a reference.MethodsWe examined the bone microstructure (Micro-CT and HE staining) and analyzed the gut microbiome and serum metabolome in rats.Results and discussionThe results revealed that L. plantarum treatment significantly restored parameters of bone microstructure, with elevated bone density, increased number and thickness of trabeculae, and decreased Tb.Sp. Gut microbiota sequencing results showed that probiotic treatment increased gut microbial diversity and the ratio of Firmicutes to Bacteroidota decreased. Beneficial bacteria abundance was significantly increased (Lachnospiraceae_NK4A136_group, Ruminococcus, UCG_005, Romboutsia, and Christensenellaceae_R_7_group), and harmful bacteria abundance was significantly decreased (Desulfovibrionaceae). According to the results of serum metabolomics, significant changes in serum metabolites occurred in different groups. These differential metabolites were predominantly enriched within the pathways of Pentose and Glucuronate Interconversions, as well as Propanoate Metabolism. Furthermore, treatment of L. plantarum significantly increased serum levels of Pyrazine and gamma-Glutamylcysteine, which were associated with inhibition of osteoclast formation and promoting osteoblast formation. Lactobacillus plantarum can protect rats from DEX-induced GIOP by mediating the “gut microbial-bone axis” promoting the production of beneficial bacteria and metabolites. Therefore L. plantarum is a potential candidate for the treatment of GIOP.

Mapping knowledge landscapes and research frontiers of gastrointestinal microbiota and bone metabolism: a text-mining study

“…Disruption of the gut microbiota has been shown to negatively impact bone health by impairing intestinal calcium absorption and modulating the balance of the Osteoprotegerin (OPG)/Receptor Activator for Nuclear Factor-κ B Ligand (RANKL) pathway through regulation of multiple hormone levels, consequently reducing bone strength and quality ( Han et al., 2023 ; Cai et al., 2024 ). Meanwhile, several probiotic strains, such as Lactobacillus and Bifidobacterium , have been demonstrated to exert significant anti-osteoporotic effects ( de Sire et al., 2022 ; Li et al., 2024 ; Zhang et al., 2024 ). Although research on the therapeutic potential of gut microbiota in osteoporosis and osteoarthritis is still in its nascent stage, most scholars envision gut microbiota intervention as a promising strategy for the diagnosis and treatment of bone metabolic diseases in the future.…”

“…In light of these findings, the study of the relationship between gut microbiota and bone metabolism has garnered widespread attention ( Sánchez Romero et al., 2021 ; Seely et al., 2021 ; de Sire et al., 2022 ; Han et al., 2023 ; Basak et al., 2024 ; Cai et al., 2024 ; Li et al., 2024 ; Zhang et al., 2024 ; Zhang et al., 2024 ). Numerous studies have endeavored to elucidate the intricate mechanisms through which gut microbiota and their metabolites influence bone formation and remodeling, resulting in a plethora of published works.…”