Modulation of bone remodeling by the gut microbiota: a new therapy for osteoporosis

Lyu, Zhengtian; Hu, Yongfei; Guo, Yuming; Liu, Dan

doi:10.1038/s41413-023-00264-x

Cited by 18 publications

(9 citation statements)

References 229 publications

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“…From a translational perspective, the manipulation of GM through prebiotics and probiotics now emerged as a promising tool for augmented bone quality in patients with osteoporosis 39 . Our findings established the association between GM disturbance and aberrant bone homeostasis of AIS.…”

Section: Discussionsupporting

confidence: 64%

Gut Microbiota Alterations in Adolescent Idiopathic Scoliosis Are Associated with Aberrant Bone Homeostasis

Li,

Liu,

et al. 2024

Orthopaedic Surgery

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ObjectiveLow bone mineral density is the major prognostic factor for adolescent idiopathic scoliosis (AIS), but the underlying mechanisms remain unclear. Accumulating evidence suggests that gut microbiota (GM) have the potential to affect bone development, and the GM signatures are altered in AIS patients. However, the effect of GM alterations on aberrant bone homeostasis in AIS remains unclear. This study aims to investigate the GM profile in AIS patients with different bone mineral density (BMD) and explore the association between GM, osteopenia, and aberrant bone turnover.MethodsA total of 126 patients with AIS who received surgical treatment were retrospectively included in this study. We analyzed the composition of the GM by 16S rRNA sequencing and BMD by dual X‐ray absorptiometry. Based on the BMD of the femur neck, the patients were divided into the osteopenia group (OPN) if the Z score < −1, and the normal (NOR) group if the Z score ≥ −1 SD compared to the healthy control. For the 16S rRNA sequencing, the raw reads were filtered to remove low‐quality reads, and operational taxonomic units were identified with the Uparse program. Weighted UniFrac distance matrix for the beta‐diversity metrics and principal coordinate analysis (PCoA) was performed, and the statistical comparisons were made with permutational multivariate analysis of variance (PERMANOVA) and analysis of similarity (ANONISM). Linear discriminant analysis effect size (LEfSe) was used to identify the enriched species in two groups. The “Random forest” was applied to determine the optimal biomarker for OPN according to the mean decrease in Gini value. The metabolic function was predicted by the Tax4Fun analysis. The Pearson correlation coefficient was used to evaluate the associations between GM species, bone turnover markers, and BMD.ResultsThe serum β‐CTX was increased in the OPN group (n = 67) compared to the NOR group (n = 59). Patients in OPN groups showed significantly decreased α diversity indicated by the Shannon index. Principal coordinate analysis (PCoA) analysis showed significant clustering of GM between OPN and NOR groups. At genus level, the Escherichia‐Shigella and Faecalibacterium were significantly enriched in the OPN group compared to that in the NOR group (p < 0.05), whereas the abundance of Prevotella was significantly decreased (p = 0.0012). The relative abundance of Megamonas and Prevotella was positively correlated with the femur BMD. The abundance of Escherichia‐Shigella was negatively correlated with femur BMD and positively correlated with serum β‐CTX levels. Functional analysis revealed significant differences in starch and sucrose metabolism, pyruvate and cysteine, and methionine metabolism between NOR and OPN groups.ConclusionThe alterations of GM in AIS patients are correlated with osteopenia. The association between enriched species, BMD, and bone turnover markers provides novel diagnostic and therapeutic targets for the clinical management of AIS.

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Section: Discussionsupporting

confidence: 64%

Gut Microbiota Alterations in Adolescent Idiopathic Scoliosis Are Associated with Aberrant Bone Homeostasis

Li,

Liu,

et al. 2024

Orthopaedic Surgery

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“…Mechanically, gut microbiota play a crucial role in the regulation of bone remodeling through both direct and indirect mechanisms. Directly, the gut microbiota exert its influence on bone remodeling by releasing extracellular vesicles or microbial metabolites, such as short-chain fatty acids, polyamines, and hydrogen sulfide . Indirectly, the gut microbiota modulates bone remodeling through its interaction with immune cells, specifically T helper cells 17 and T regulatory cells, as well as hormones such as estrogen and parathyroid hormone .…”

Section: Introductionmentioning

confidence: 99%

Phytosterols Protect against Osteoporosis by Regulating Gut Microbiota

Xiao,

Wang,

Zhu

et al. 2023

J. Agric. Food Chem.

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Osteoporosis is increasingly prevalent worldwide, representing a major health burden. However, there is a lack of nutritional strategies for osteoporotic therapy. Phytosterols, as natural bioactive compounds, have the potential to alleviate osteoporosis. In this study, a glucocorticoid-induced osteoporosis mouse model and treatment with low and high concentrations of phytosterols for 4 weeks were established. The results demonstrated that compared to the control group, low-concentration phytosterols (LP) (0.3 mg/mL) increased bone mass, improved trabecular microstructure, reduced serum levels of cross-linked C-telopeptide of type I collagen (CTX-1), and elevated serum levels of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3). Conversely, high-concentration phytosterols (0.5 mg/mL) showed no effect. Additionally, we validated the effect of LP in ameliorating osteoporosis using an ovariectomized (OVX)-induced osteoporosis mouse model. Mechanistically, phytosterols altered the microbial composition to counteract glucocorticoid-induced gut microbiota disorder and improve the length and morphology of the small intestine. Particularly, based on selection strategy and correlation analysis, phytosterols increased the relative abundance of Ruminococcus and decreased the relative abundance of Bilophila, which were significantly associated with glucocorticoid-induced osteoporosis indications. Overall, these findings suggest that phytosterols regulate gut microbiota to increase bone mass, thereby exerting an antiosteoporotic effect.

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“…Despite the widely applied anti‐resorptive agents (such as bisphosphonates (Rachner et al., 2011) and denosumab (Bone et al., 2017) and anabolic drugs (such as parathyroid hormone (Neer et al., 2001), innovative treatment strategy to regulate the osteoblasts‐osteoclasts balance are emphasized (Zhou et al., 2021). Recently, the influence of gut microbes on bone metabolism has received increasing attention (Lyu et al., 2023). Microbes could affect human health by influencing symbiotic flora to inhibit pathogens, regulating host immune responses, increasing epithelial barrier function, and enhancing tight junction function, which are considered to be the first generation of the gut‐bone axis (Zaiss et al., 2019).…”

Section: Discussionmentioning

confidence: 99%

Synthetic biology‐based bacterial extracellular vesicles displaying BMP‐2 and CXCR4 to ameliorate osteoporosis

Liu,

Song,

Zhang

et al. 2024

J of Extracellular Vesicle

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Osteoporosis (OP) is a systematic bone disease characterized by low bone mass and fragile bone microarchitecture. Conventional treatment for OP has limited efficacy and long‐term toxicity. Synthetic biology makes bacterial extracellular vesicle (BEVs)‐based therapeutic strategies a promising alternative for the treatment of OP. Here, we constructed a recombinant probiotics Escherichia coli Nissle 1917‐pET28a‐ClyA‐BMP‐2‐CXCR4 (ECN‐pClyA‐BMP‐2‐CXCR4), in which BMP‐2 and CXCR4 were overexpressed in fusion with BEVs surface protein ClyA. Subsequently, we isolated engineered BEVs‐BMP‐2‐CXCR4 (BEVs‐BC) for OP therapy. The engineered BEVs‐BC exhibited great bone targeting in vivo. In addition, BEVs‐BC had good biocompatibility and remarkable ability to promote osteogenic differentiation of BMSCs. Finally, the synthetic biology‐based BEVs‐BC significantly prevented the OP in an ovariectomized (OVX) mouse model. In conclusion, we constructed BEVs‐BC with both bone‐targeting and bone‐forming in one‐step using synthetic biology, which provides an effective strategy for OP and has great potential for industrialization.

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Modulation of bone remodeling by the gut microbiota: a new therapy for osteoporosis

Cited by 18 publications

References 229 publications

Gut Microbiota Alterations in Adolescent Idiopathic Scoliosis Are Associated with Aberrant Bone Homeostasis

Gut Microbiota Alterations in Adolescent Idiopathic Scoliosis Are Associated with Aberrant Bone Homeostasis

Phytosterols Protect against Osteoporosis by Regulating Gut Microbiota

Synthetic biology‐based bacterial extracellular vesicles displaying BMP‐2 and CXCR4 to ameliorate osteoporosis

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