Intestinal microbiota: a potential target for the treatment of postmenopausal osteoporosis

Xu, Xin; Jia, Xiaoyue; Mo, Longyi; Liu, Chengcheng; Zheng, Liwei; Yuan, Quan; Zhou, Xuedong

doi:10.1038/boneres.2017.46

Cited by 147 publications

(148 citation statements)

References 246 publications

(326 reference statements)

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“…Increased gut permeability causes an invasion of gut lumen antigenic components and subsequent inflammatory responses (Xu, Jia et al, 2017). The active immune cells lining at the gut lumen release some soluble osteoclastogenic cytokines into the circulation and modulate systemic bone metabolism (Li, Toraldo et al, 2007, Pacifici, 2016.…”

Section: Discussionmentioning

confidence: 99%

An emerging role ofPrevotella histicolaon estrogen-deficiency induced bone loss through the gut microbiota-bone axis

Wang

Chen

et al. 2020

Preprint

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Gut microbiota (GM)-bone axis has emerged as a crucial mediator in the maintenance of bone homeostasis. Estrogen-deficiency induced bone loss is closely associated with an altered GM.However, the underlying mechanisms remain not fully understood. To this end, feces samples collected from the postmenopausal patients with osteoporosis (PMO) and with normal bone mass (PMN) were examined by 16s rRNA gene sequencing. We found that GM in PMO group was featured by a significant decreased proportion of genus Prevotella in comparison with that in the PMN group. Next, Prevotella histicola (P.histicola), a typical specie of Prevotella, was orally given to the mice following the ovariectomy (OVX) procedure and it significantly prevented OVX induced bone loss. Mechanistically, the protective effects of P.histicola on bone mass were found to be associated with the inhibition of osteoclastic resorption by attenuating osteoclastogenic cytokines expression and ameliorating gut permeability. Thus, P.histicola may prevent estrogendeficiency induced bone loss through the GM-bone axis.

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Section: Discussionmentioning

confidence: 99%

An emerging role ofPrevotella histicolaon estrogen-deficiency induced bone loss through the gut microbiota-bone axis

Wang

Chen

et al. 2020

Preprint

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“…By analyzing the biological functions behind, we found that 24 novel candidate genes directly affect the pathways closely related to the development of osteoporosis in our results: IBSP, EIF2B2, CD44, FEN1, UBA7, MARCO, ATF1,CBFB, G6PC3, SLC11A2, GAL, CCR3, MST1R, PLEKHM1, ATRIP, CCDC36, AKAP7, EPRS, CTSB, ASB16-AS1, CRHR1, FADS1, MAP1LC3A, MAEA. For example, SLC11A2 enriched in mineral absorption pathway regulates the fine-tuned balance between bone resorption and bone formation and thus affects bone density (Xu et al 2017), shown in Supplementary Figure 7. In the other hand, 129 novel candidate genes seem exerting their biological functions to affect the development of osteoporosis through protein-protein interaction networks.…”

Section: Discussionmentioning

confidence: 99%

Integrating genome-wide association and transcriptome predicted model identify novel target genes with osteoporosis

Yin

Zhu

et al. 2019

Preprint

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Osteoporosis (OP) is a highly polygenetic disease which is usually characterized by low bone mineral density. Genome-wide association studies (GWAS) have identified hundreds of genetic loci associated with bone mineral density. However, the biological mechanisms of these loci remain elusive. To identify potential causal genes of the associated loci, we detected trait-gene expression associations by transcriptome-wide association study (TWAS) method. It directly imputes gene expression effects from GWAS data, using a statistical prediction model trained on GTEx reference transcriptome data, with blood and skeletal tissues data. Then we performed a colocalization analysis to evaluate the posterior probability of biological patterns: association characterized by a single shared causal variant or two distinct causal variants. The ultimate analysis identified 276 candidate genes, including 3 novel loci, 204 novel candidate genes and 69 replicated from GWAS. The 3 novel loci located at chr6: 72417543, chr15: 69601206, chr21: 30530692, mapping to gene RIMS1, SPESP1, MAP3K7CL. The results of colocalization analysis indicated that 142 of them showing strong evidence of a single shared causal variant and 134 of them showing evidence of joint causal variants. Their biological function was directly or indirectly associated with the occurrence of OP validated by VarElect tool. Several important OP-associated pathways were detected by protein-protein interaction and pathway enrichment analysis. Target genes were further enriched for differential expression genes in osteoblasts expression profiles, e.g. IBSP, affecting calcium and hydroxyapatite binding, and CD44, regulating alternative splicing of gene transcription. Transcriptome fine-mapping identifies more disease-related genes and provide additional insight into the development of novel targeted therapeutics to treat OP.

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“…Conventional therapeutic interventions on osteoporosis include general lifestyle changing (e.g., balanced diet and regular exercise) (6), and intake of approved drugs (e.g., oestrogen and bisphosphonates) (7). In recent years, a series of studies suggested that gut microbiota colonizing in the intestinal tract not only affected the nutrition metabolism, but also contributed to the occurrence and progression of osteoporosis (8). Das et al reported there were differences of gut microbiota composition between osteoporosis /osteopenia and controls with an Irish cohort of older adults (9).…”

Section: Introductionmentioning

confidence: 99%

Alteration of fecal microbial compositions and bacterial taxa in female osteoporotic patients

Zhu

Liu

Pan

et al. 2020

Preprint

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Contributions to this study：post doctorate，Responsible for the 34 establishment, detection, analysis and quality control of the database of intestinal 35 flora structure and gene polymorphism) 36 37 Cuifeng Zhu, Jianguo Liu and Yong Pan contributed equally to this work. Author 38 order was determined on the basis of seniority. ( CuiFeng Zhu, Department 39 director of Dept of Clinical Nutrition, chief physician, master tutor of Shenzhen 40 hospital of southern medical university. Post doctor fellows of Dept of 41 endocrinology of university of Hong Kong & The State Key laboratory of 42 Pharmaceutical Biotechnology. E-mail :1794371266@qq.com(Contributions to 43 this study: chief physician of Nutrition department and post doctorate, responsible 44 for the design and implementation of this project, data collation and paper 45 writing); JianGuo Liu, Associate chief physician, Department director of Dept 46 of Health management of Shenzhen hospital of southern medical University. E-47 3 / 25 mail : JgLiu123@163.com(Contribution to this study: general practitioner at 48 health management center, responsible for case collection and data collation); , 13570469574 66 (Contribution to this study：Nutrition department attending physician, in 67 charge of the medical history of selected patients, menstrual history, life history 68 and other data survey) 69 4 / 25 Abstract 120 Background: Gut microbiota, mainly characterized by fecal bacterial 121 compositions, affects human immune system and pathophysiological 122 development. Our aim was to measure the quantitative differences of 123 fecal bacterial compositions between osteoporotic patients and healthy 124 subjects, and to identify novel bacterial taxa that speculate the 125 incidence of osteoporosis in female. 126 127 Method: We recruited 104 female subjects, including 45 osteoporotic 128 individuals and 59 healthy control. Fecal samples were collected for 129 further analysis by 16S rRNA quantitative arrays and bioinformatics 130 analysis. 131 132 Results: Analyses of α-and β-diversity demonstrated that the diversity 133 and composition of fecal bacterial compositions were both significant 134 different in osteoporosis group, as compared with healthy group. 135 Multiple bacterial genera were significantly increased (e.g., Roseburia 136 and Bacteroides) or decreased (e.g., Streptococcus and Dorea) in the 137 osteoporotic cases. Furthermore, the osteoporosiscould be efficiently 138

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Intestinal microbiota: a potential target for the treatment of postmenopausal osteoporosis

Cited by 147 publications

References 246 publications

An emerging role ofPrevotella histicolaon estrogen-deficiency induced bone loss through the gut microbiota-bone axis

An emerging role ofPrevotella histicolaon estrogen-deficiency induced bone loss through the gut microbiota-bone axis

Integrating genome-wide association and transcriptome predicted model identify novel target genes with osteoporosis

Alteration of fecal microbial compositions and bacterial taxa in female osteoporotic patients

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