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      Diversity analysis of gut microbiota in osteoporosis and osteopenia patients

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          Abstract

          Some evidence suggests that bone health can be regulated by gut microbiota. To better understand this, we performed 16S ribosomal RNA sequencing to analyze the intestinal microbial diversity in primary osteoporosis (OP) patients, osteopenia (ON) patients and normal controls (NC). We observed an inverse correlation between the number of bacterial taxa and the value of bone mineral density. The diversity estimators in the OP and ON groups were increased compared with those in the NC group. Beta diversity analyses based on hierarchical clustering and principal coordinate analysis (PCoA) could discriminate the NC samples from OP and ON samples. Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria constituted the four dominant phyla in all samples. Proportion of Firmicutes was significantly higher and Bacteroidetes was significantly lower in OP samples than that in NC samples ( p < 0.05), Gemmatimonadetes and Chloroflexi were significantly different between OP and NC group as well as between ON and NC group ( p < 0.01). A total of 21 genera with proportions above 1% were detected and Bacteroides accounted for the largest proportion in all samples. The Blautia, Parabacteroides and Ruminococcaceae genera differed significantly between the OP and NC group ( p < 0.05). Linear discriminant analysis (LDA) results showed one phylum community and seven phylum communities were enriched in ON and OP, respectively. Thirty-five genus communities, five genus communities and two genus communities were enriched in OP, ON and NC, respectively. The results of this study indicate that gut microbiota may be a critical factor in osteoporosis development, which can further help us search for novel biomarkers of gut microbiota in OP and understand the interaction between gut microbiota and bone health.

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          Most cited references21

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          Control of osteoblast function and regulation of bone mass.

          The skeleton is an efficient 'servo' (feedback-controlled/steady-state) system that continuously integrates signals and responses which sustain its functions of delivering calcium while maintaining strength. In many individuals, bone mass homeostasis starts failing in midlife, leading to bone loss, osteoporosis and debilitating fractures. Recent advances, spearheaded by genetic information, offer the opportunity to stop or reverse this downhill course.
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            Gut microbiota induce IGF-1 and promote bone formation and growth.

            Appreciation of the role of the gut microbiome in regulating vertebrate metabolism has exploded recently. However, the effects of gut microbiota on skeletal growth and homeostasis have only recently begun to be explored. Here, we report that colonization of sexually mature germ-free (GF) mice with conventional specific pathogen-free (SPF) gut microbiota increases both bone formation and resorption, with the net effect of colonization varying with the duration of colonization. Although colonization of adult mice acutely reduces bone mass, in long-term colonized mice, an increase in bone formation and growth plate activity predominates, resulting in equalization of bone mass and increased longitudinal and radial bone growth. Serum levels of insulin-like growth factor 1 (IGF-1), a hormone with known actions on skeletal growth, are substantially increased in response to microbial colonization, with significant increases in liver and adipose tissue IGF-1 production. Antibiotic treatment of conventional mice, in contrast, decreases serum IGF-1 and inhibits bone formation. Supplementation of antibiotic-treated mice with short-chain fatty acids (SCFAs), products of microbial metabolism, restores IGF-1 and bone mass to levels seen in nonantibiotic-treated mice. Thus, SCFA production may be one mechanism by which microbiota increase serum IGF-1. Our study demonstrates that gut microbiota provide a net anabolic stimulus to the skeleton, which is likely mediated by IGF-1. Manipulation of the microbiome or its metabolites may afford opportunities to optimize bone health and growth.
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              The human microbiome: our second genome.

              The human genome has been referred to as the blueprint of human biology. In this review we consider an essential but largely ignored overlay to that blueprint, the human microbiome, which is composed of those microbes that live in and on our bodies. The human microbiome is a source of genetic diversity, a modifier of disease, an essential component of immunity, and a functional entity that influences metabolism and modulates drug interactions. Characterization and analysis of the human microbiome have been greatly catalyzed by advances in genomic technologies. We discuss how these technologies have shaped this emerging field of study and advanced our understanding of the human microbiome. We also identify future challenges, many of which are common to human genetic studies, and predict that in the future, analyzing genetic variation and risk of human disease will sometimes necessitate the integration of human and microbial genomic data sets.
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                Author and article information

                Contributors
                Journal
                PeerJ
                PeerJ
                peerj
                peerj
                PeerJ
                PeerJ Inc. (San Francisco, USA )
                2167-8359
                15 June 2017
                2017
                : 5
                : e3450
                Affiliations
                [1 ]Hong Hui Hospital, Xi’an Jiaotong University , Xi’an, China
                [2 ]The Tenth Research Institute of Telecommunications Technology , Xi’an, China
                [3 ]Department of Pathogenic Biology and Immunology, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education of China, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center , Xi’an, China
                Article
                3450
                10.7717/peerj.3450
                5474093
                28630804
                21165820-3d2d-4a6e-8bd2-f36825130d19
                ©2017 Wang et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.

                History
                : 29 March 2017
                : 19 May 2017
                Funding
                Funded by: China Postdoctoral Science Foundation
                Award ID: 2017M613176
                Award ID: 2017M613177
                Funded by: National Natural Science Foundation of China
                Award ID: 81601898
                Funded by: Research Foundation of Xi’an Hong-Hui Hospital
                Award ID: YJ2016013
                This project was funded by the China Postdoctoral Science Foundation (No. 2017M613176, No. 2017M613177), the National Natural Science Foundation of China (No. 81601898) and the Research Foundation of Xi’an Hong-Hui Hospital (No. YJ2016013). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Microbiology
                Orthopedics
                Rheumatology

                osteoporosis,16s ribosomal rna,diversity analysis,bone mineral density,gut microbiota

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