Intermittent Parathyroid Hormone Alters Gut Microbiota in Ovariectomized Osteoporotic Rats

Zhou, Jiaming; Wang, Rui; Zhao, Rui; Guo, Xing; Gou, Pengguo; Bai, He; Lei, Ping; Xue, Yuan

doi:10.1111/os.13419

Cited by 9 publications

(8 citation statements)

References 47 publications

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“…According to a case-control study, the level of Family Rikenellaceae was higher in the low BMD group and Rikenellaceae might have an adverse impact on bone resorption and bone density ( 36 ). Similarly, compared with the OVX group, the anti-osteoporosis treatment group increased the abundances of Lactobacillus_reuteri , Muribaculaceae , and Clostridia that were reported to increase bone mass and inhibited the relative abundance of Rikenellaceae ( 37 ).…”

Section: Discussionmentioning

confidence: 99%

Causal effects of specific gut microbiota on bone mineral density: a two-sample Mendelian randomization study

et al. 2023

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BackgroundRecent studies have reported that the gut microbiota is essential for preventing and delaying the progression of osteoporosis. Nonetheless, the causal relationship between the gut microbiota and the risk of osteoporosis has not been fully revealed.MethodsA two-sample Mendelian randomization (MR) analysis based on a large-scale genome-wide association study (GWAS) was conducted to investigate the causal relationship between the gut microbiota and bone mineral density (BMD). Instrumental variables for 211 gut microbiota taxa were obtained from the available GWAS meta-analysis (n = 18,340) conducted by the MiBioGen consortium. The summary-level data for BMD were from the Genetic Factors for Osteoporosis (GEFOS) Consortium, which involved a total of 32,735 individuals of European ancestry. The inverse variance-weighted (IVW) method was performed as a primary analysis to estimate the causal effect, and the robustness of the results was tested via sensitivity analyses by using multiple methods. Finally, a reverse MR analysis was applied to evaluate reverse causality.ResultsAccording to the IVW method, we found that nine, six, and eight genetically predicted gut microbiota were associated with lumbar spine (LS) BMD, forearm (FA) BMD, and femoral neck (FN) BMD, respectively. Among them, the higher genetically predicted Genus Prevotella9 level was correlated with increased LS-BMD [β = 0.125, 95% confidence interval (CI): 0.050–0.200, P = 0.001] and FA-BMD (β = 0.129, 95% CI: 0.007–0.251, P = 0.039). The higher level of genetically predicted Family Prevotellaceae was associated with increased FA-BMD (β = 0.154, 95% CI: 0.020–0.288, P = 0.025) and FN-BMD (β = 0.080, 95% CI: 0.015–0.145, P = 0.016). Consistent directional effects for all analyses were observed in both the MR-Egger and weighted median methods. Subsequently, sensitivity analyses revealed no heterogeneity, directional pleiotropy, or outliers for the causal effect of specific gut microbiota on BMD (P > 0.05). In reverse MR analysis, there was no evidence of reverse causality between LS-BMD, FA-BMD, and FN-BMD and gut microbiota (P > 0.05).ConclusionGenetic evidence suggested a causal relationship between the gut microbiota and BMD and identified specific bacterial taxa that regulate bone mass variation. Further exploration of the potential microbiota-related mechanisms of bone metabolism might provide new approaches for the prevention and treatment of osteoporosis.

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Section: Discussionmentioning

confidence: 99%

Causal effects of specific gut microbiota on bone mineral density: a two-sample Mendelian randomization study

et al. 2023

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“…Muribaculaceae and Parasutterella were positively correlated with BMD, BV/TV, Tb.N, and B-ALP. Palmatine and intermittent parathyroid hormone (PTH) have been reported to increase the abundance of Muribaculaceae and increase bone mass in OVX rats [ 37 , 38 ]. Parasutterella is involved in Kefir Peptides’ prevention of estrogen deficiency-induced bone loss and GM disorders [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

Nodakenin Ameliorates Ovariectomy-Induced Bone Loss by Regulating Gut Microbiota

Liu,

Chen,

Wang

et al. 2024

Molecules

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Disordered gut microbiota (GM) structure and function may contribute to osteoporosis (OP). Nodakenin has been shown to ameliorate osteoporosis; however, its anti-osteoporotic mechanism is unknown. This study aimed to further reveal the mechanism of the anti-osteoporotic action of nodakenin from the perspective of the microbiome and metabolome. An osteoporosis model was induced in mice through ovariectomy (OVX), with bone mass and microstructure assessed using μCT. Subsequently, ELISA and histologic examination were used to detect biochemical indicators of bone conversion and intestinal morphology. Using metabolomics and 16S rRNA sequencing, it was possible to determine the composition and abundance of the gut microbiota in feces. The results revealed that nodakenin treatment improved the bone microstructure and serum levels of bone turnover markers, and increased the intestinal mucosal integrity. 16S rRNA sequencing analysis revealed that nodakenin treatment decreased the relative abundance of Firmicutes and Patescibacteria, as well as the F/B ratio, and elevated the relative abundance of Bacteroidetes in OVX mice. In addition, nodakenin enhanced the relative abundance of Muribaculaceae and Allobaculum, among others, at the genus level. Moreover, metabolomics analysis revealed that nodakenin treatment significantly altered the changes in 113 metabolites, including calcitriol. A correlation analysis revealed substantial associations between various gut microbiota taxa and both the osteoporosis phenotype and metabolites. In summary, nodakenin treatment alleviated OVX-induced osteoporosis by modulating the gut microbiota and intestinal barrier.

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“…Lactobacillus is thought to be a beneficial bacterium that potentially affects immune-related bone health by regulating proinflammatory cytokines and markers related to bone metabolism ( 44 ). Muribaculaceae belongs to the phylum Bacteroides and was renamed by Ilias et al Studies have shown that intermittent parathyroid hormone (PTH) can increase the abundance of Muribaculaceae and increase bone mass in OVX rats ( 45 ). An epidemiological analysis showed that Lachnospiraceae abundance was reduced in populations with low bone mineral density (BMD).…”

Section: Discussionmentioning

confidence: 99%

The mechanism of palmatine-mediated intestinal flora and host metabolism intervention in OA-OP comorbidity rats

Jie

Gao

et al. 2023

Front. Med.

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BackgroundErXian decoction is a Chinese herbal compound that can prevent and control the course of osteoarthritis (OA) and osteoporosis (OP). OP and OA are two age-related diseases that often coexist in elderly individuals, and both are associated with dysregulation of the gut microbiome. In the initial study, Palmatine (PAL) was obtained by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and network pharmacological screening techniques, followed by 16S rRNA sequencing and serum metabolomics of intestinal contents, to explore the mechanism of PAL in the treatment of OA and OP.MethodsThe rats selected for this study were randomly divided into three groups: a sham group, an OA-OP group and a PAL group. The sham group was intragastrically administered normal saline solution, and the PLA group was treated with PAL for 56 days. Through microcomputed tomography (micro-CT), ELISA, 16S rRNA gene sequencing and non-targeted metabonomics research, we explored the potential mechanism of intestinal microbiota and serum metabolites in PAL treatment of OA-OP rats.ResultsPalmatine significantly repair bone microarchitecture of rat femur in OA-OP rats and improved cartilage damage. The analysis of intestinal microflora showed that PAL could also improve the intestinal microflora disorder of OA-OP rats. For example, the abundance of Firmicutes, Bacteroidota, Actinobacteria, Lactobacillus, unclassified_f_Lachnospiraceae, norank_f_Muribaculaceae, Lactobacillaceae, Lachnospiraceae and Muribaculaceae increased after PAL intervention. In addition, the results of metabolomics data analysis showed that PAL also change the metabolic status of OA-OP rats. After PAL intervention, metabolites such as 5-methoxytryptophol, 2-methoxy acetaminophen sulfate, beta-tyrosine, indole-3-carboxylic acid-O-sulfate and cyclodopa glucoside increased. Association analysis of metabolomics and gut microbiota (GM) showed that the communication of multiple flora and different metabolites played an important role in OP and OA.ConclusionPalmatine can improve cartilage degeneration and bone loss in OA-OP rats. The evidence we provided supports the idea that PAL improves OA-OP by altering GM and serum metabolites. In addition, the application of GM and serum metabolomics correlation analysis provides a new strategy for uncovering the mechanism of herbal treatment for bone diseases.

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Intermittent Parathyroid Hormone Alters Gut Microbiota in Ovariectomized Osteoporotic Rats

Cited by 9 publications

References 47 publications

Causal effects of specific gut microbiota on bone mineral density: a two-sample Mendelian randomization study

Causal effects of specific gut microbiota on bone mineral density: a two-sample Mendelian randomization study

Nodakenin Ameliorates Ovariectomy-Induced Bone Loss by Regulating Gut Microbiota

The mechanism of palmatine-mediated intestinal flora and host metabolism intervention in OA-OP comorbidity rats

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