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On-line Access: 2022-12-15

Received: 2022-06-29

Revision Accepted: 2022-08-11

Crosschecked: 2022-12-15

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Shaohui ZONG


Gaofeng ZENG


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Journal of Zhejiang University SCIENCE B 2022 Vol.23 No.12 P.1002-1013


Changes in the gut microbiota of osteoporosis patients based on 16S rRNA gene sequencing: a systematic review and meta-analysis

Author(s):  Rui HUANG, Pan LIU, Yiguang BAI, Jieqiong HUANG, Rui PAN, Huihua LI, Yeping SU, Quan ZHOU, Ruixin MA, Shaohui ZONG, Gaofeng ZENG

Affiliation(s):  College of Public Hygiene of Guangxi Medical University, Nanning 530021, China; more

Corresponding email(s):   xiaohui3008@126.com, fengfeng_388@126.com

Key Words:  Osteoporosis, Microbiome, Intestinal, 16S ribosomal RNA (rRNA) sequencing

Rui HUANG, Pan LIU, Yiguang BAI, Jieqiong HUANG, Rui PAN, Huihua LI, Yeping SU, Quan ZHOU, Ruixin MA, Shaohui ZONG, Gaofeng ZENG. Changes in the gut microbiota of osteoporosis patients based on 16S rRNA gene sequencing: a systematic review and meta-analysis[J]. Journal of Zhejiang University Science B, 2022, 23(12): 1002-1013.

@article{title="Changes in the gut microbiota of osteoporosis patients based on 16S rRNA gene sequencing: a systematic review and meta-analysis",
author="Rui HUANG, Pan LIU, Yiguang BAI, Jieqiong HUANG, Rui PAN, Huihua LI, Yeping SU, Quan ZHOU, Ruixin MA, Shaohui ZONG, Gaofeng ZENG",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Changes in the gut microbiota of osteoporosis patients based on 16S rRNA gene sequencing: a systematic review and meta-analysis
%A Pan LIU
%A Yiguang BAI
%A Jieqiong HUANG
%A Rui PAN
%A Huihua LI
%A Yeping SU
%A Quan ZHOU
%A Ruixin MA
%A Shaohui ZONG
%A Gaofeng ZENG
%J Journal of Zhejiang University SCIENCE B
%V 23
%N 12
%P 1002-1013
%@ 1673-1581
%D 2022
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2200344

T1 - Changes in the gut microbiota of osteoporosis patients based on 16S rRNA gene sequencing: a systematic review and meta-analysis
A1 - Rui HUANG
A1 - Pan LIU
A1 - Yiguang BAI
A1 - Jieqiong HUANG
A1 - Rui PAN
A1 - Huihua LI
A1 - Yeping SU
A1 - Quan ZHOU
A1 - Ruixin MA
A1 - Shaohui ZONG
A1 - Gaofeng ZENG
J0 - Journal of Zhejiang University Science B
VL - 23
IS - 12
SP - 1002
EP - 1013
%@ 1673-1581
Y1 - 2022
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2200344

Backgroundosteoporosis (OP) has become a major public health issue, threatening the bone health of middle-aged and elderly people from all around the world. Changes in the gut microbiota (GM) are correlated with the maintenance of bone mass and bone quality. However, research results in this field remain highly controversial, and no systematic review or meta-analysis of the relationship between GM and OP has been conducted. This paper addresses this shortcoming, focusing on the difference in the GM abundance between OP patients and healthy controls based on previous 16S ribosomal RNA (rRNA) gene sequencing results, in order to provide new clinical reference information for future customized prevention and treatment options of OP.
MethodsAccording to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), we comprehensively searched the databases of PubMed, Web of Science, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI). In addition, we applied the R programming language version 4.0.3 and Stata 15.1 software for data analysis. We also implemented the Newcastle-Ottawa Scale (NOS), funnel plot analysis, sensitivity analysis, Egger’s test, and Begg’s test to assess the risk of bias.
ResultsThis research ultimately considered 12 studies, which included the fecal GM data of 2033 people (604 with OP and 1429 healthy controls). In the included research papers, it was observed that the relative abundance of Lactobacillus and Ruminococcus increased in the OP group, while the relative abundance for Bacteroides of Bacteroidetes increased (except for Ireland). Meanwhile, Firmicutes, Blautia, Alistipes, Megamonas, and Anaerostipes showed reduced relative abundance in Chinese studies. In the linear discriminant analysis Effect Size (LEfSe) analysis, certain bacteria showed statistically significant results consistently across different studies.
ConclusionsThis observational meta-analysis revealed that changes in the GM were correlated with OP, and variations in some advantageous GM might involve regional differences.

基于16S rRNA基因测序技术揭示骨质疏松症患者肠道菌群的改变:一项系统评价和荟萃分析

概要:骨质疏松症(osteoporosis,OP)已成为严重威胁全球中老年人骨健康的重大公共卫生问题。肠道菌群(gut microbiota,GM)的改变与维持骨量和骨质量有关。然而,相关研究结果仍存在很大争议,目前尚没有研究对肠道菌群和骨质疏松间关系进行过系统评价和荟萃分析。本研究通过对骨质疏松症患者和健康人群之间肠道菌群差异的既往16S rRNA基因测序结果进行系统评价和荟萃分析,以期为未来个体化预防和治疗骨质疏松症提供新的临床参考。这项观察性的荟萃分析显示,肠道菌群的改变与骨质疏松症之间存在关联,并且一些优势菌群的变化可能存在地域差异。

关键词:骨质疏松症;微生物群;肠道;16S rRNA测序

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1]AkbariS, Rasouli-GhahroudiAA, 2018. Vitamin K and bone metabolism: a review of the latest evidence in preclinical studies. Biomed Res Int, 2018:4629383.

[2]Anonymous, 1993. Consensus development conference: diagnosis, prophylaxis, and treatment of osteoporosis. Am J Med, 94(6):646-650.

[3]AtkinsGJ, WelldonKJ, WijenayakaAR, et al., 2009. Vitamin K promotes mineralization, osteoblast-to-osteocyte transition, and an anticatabolic phenotype by γ-carboxylation-dependent and -independent mechanisms. Am J Physiol Cell Physiol, 297(6):C1358-C1367.

[4]BakerRG, HaydenMS, GhoshS, 2011. NF‍-‍‍κB, inflammation, andmetabolic disease. Cell Metab, 13(1):11-22.

[5]BrittonRA, IrwinR, QuachD, et al., 2014. Probiotic L. reuteri treatment prevents bone loss in a menopausal ovariectomized mouse model. J Cell Physiol, 229(11):1822-1830.

[6]BuiTPN, Mannerås-HolmL, PuschmannR, et al., 2021. Conversion of dietary inositol into propionate and acetate by commensal Anaerostipes associates with host health. Nat Commun, 12:4798.

[7]Crespo-PiazueloD, LawlorPG, RanjitkarS, et al., 2021. Intestinal microbiota modulation and improved growth in pigs with post-weaning antibiotic and ZnO supplementation but only subtle microbiota effects with Bacillus altitudinis. Sci Rep, 11:23304.

[8]DanneC, RyzhakovG, Martínez-LópezM, et al., 2017. A large polysaccharide produced by Helicobacter hepaticus induces an anti-inflammatory gene signature in macrophages. Cell Host Microbe, 22(6):733-745.e5.

[9]DasM, CroninO, KeohaneDM, et al., 2019. Gut microbiota alterations associated with reduced bone mineral density in older adults. Rheumatology (Oxford), 58(12):2295-2304.

[10]DingC, 2017. The Effects of LPS on the Proliferation and Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells and the Study on the Related Mechanisms. MS Thesis, Naval Medical University, Shanghai, China(in Chinese).

[11]DuvalletC, 2018. Meta-analysis generates and prioritizes hypotheses for translational microbiome research. Microb Biotechnol, 11(2):273-276.

[12]GuptaVK, PaulS, DuttaC, 2017. Geography, ethnicity or subsistence-specific variations in human microbiome composition and diversity. Front Microbiol, 8:1162.

[13]HeJQ, XuSB, ZhangBZ, et al., 2020. Gut microbiota and metabolite alterations associated with reduced bone mineral density or bone metabolic indexes in postmenopausal osteoporosis. Aging (Albany NY), 12(9):8583-8604.

[14]HouM, XuGL, RanMS, et al., 2021. APOE-ε4 carrier status and gut microbiota dysbiosis in patients with alzheimer disease. Front Neurosci, 15:619051.

[15]JafarnejadS, DjafarianK, FazeliMR, et al., 2017. Effects of a multispecies probiotic supplement on bone health in osteopenic postmenopausal women: a randomized, double-blind, controlled trial. J Am Coll Nutr, 36(7):497-506.

[16]JanssonPA, CuriacD, Lazou AhrénI, et al., 2019. Probiotic treatment using a mix of three Lactobacillus strains for lumbar spine bone loss in postmenopausal women: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet Rheumatol, 1(3):e154-e162.

[17]JuanolaO, PiñeroP, Gómez-HurtadoI, et al., 2018. Regulatory T cells restrict permeability to bacterial antigen translocation and preserve short-chain fatty acids in experimental cirrhosis. Hepatol Commun, 2(12):1610-1623.

[18]Juárez-FernándezM, PorrasD, García-MediavillaMV, et al., 2020. Aging, gut microbiota and metabolic diseases: management through physical exercise and nutritional interventions. Nutrients, 13(1):16.

[19]KhokhlovaEV, SmeianovVV, EfimovBA, et al., 2012. Anti-inflammatory properties of intestinal Bifidobacterium strains isolated from healthy infants. Microbiol Immunol, 56(1):27-39.

[20]LambertMNT, ThyboCB, LykkeboeS, et al., 2017. Combined bioavailable isoflavones and probiotics improve bone status and estrogen metabolism in postmenopausal osteopenic women: a randomized controlled trial. Am J Clin Nutr, 106(3):909-920.

[21]LiC, HuangQ, YangR, et al., 2019. Gut microbiota composition and bone mineral loss-epidemiologic evidence from individuals in Wuhan, China. Osteoporos Int, 30(5):‍1003-1013.

[22]LiLS, 2019. Study of Correlation Between Structural Characteristics of Gut Microbiota and TH17/Treg Ratio in Osteoporosis. MS Thesis, Southern Medical University, Guangzhou, China(in Chinese).

[23]LiSY, WangZL, YangY, et al., 2017. Lachnospiraceae shift in the microbial community of mice faecal sample effects on water immersion restraint stress. AMB Express, 7:82.

[24]LiangC, PengSL, LiJ, et al., 2018. Inhibition of osteoblastic Smurf1 promotes bone formation in mouse models of distinctive age-related osteoporosis. Nat Commun, 9:3428.

[25]LingCW, MiaoZL, XiaoML, et al., 2021. The association of gut microbiota with osteoporosis is mediated by amino acid metabolism: multiomics in a large cohort. J Clin Endocrinol Metab, 106(10):e3852-e3864.

[26]LiuXM, MaoBY, GuJY, et al., 2021. Blautia—a new functional genus with potential probiotic properties? Gut Microbes, 13(1):1875796.

[27]LiuZJ, XuC, TianR, et al., 2021. Screening beneficial bacteriostatic lactic acid bacteria in the intestine and studies of bacteriostatic substances. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 22(7):533-547.

[28]LyuJ, ZhaoHP, YuY, et al., 2021a. Composition and gene function of intestinal microbiota in male osteoporotic patients. Chin J Osteoporosis Bone Miner Res, 14(5):457-469 (in Chinese).

[29]LyuJ, ZhaoHP, YuY, et al., 2021b. Profile and gene functional analysis of gut microbiota in women with postmenopausal osteoporosis. Chin J Microbiol Immunol, 41(11):‍867-874 (in Chinese).

[30]MandatoriD, PelusiL, SchiavoneV, et al., 2021. The dual role of vitamin K2 in “bone-vascular crosstalk”: opposite effects on bone loss and vascular calcification. Nutrients, 13(4):1222.

[31]MccabeLR, IrwinR, SchaeferL, et al., 2013. Probiotic use decreases intestinal inflammation and increases bone density in healthy male but not female mice. J Cell Physiol, 228(8):1793-1798.

[32]MoherD, LiberatiA, TetzlaffJ, et al., 2009. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ, 339:b2535.

[33]NaguraN, KomatsuJ, IwaseH, et al., 2015. Effects of the combination of vitamin K and teriparatide on the bone metabolism in ovariectomized rats. Biomed Rep, 3(3):295-300.

[34]NilssonAG, SundhD, BäckhedF, et al., 2018. Lactobacillus reuteri reduces bone loss in older women with low bone mineral density: a randomized, placebo-controlled, double-blind, clinical trial. J Intern Med, 284(3):307-317.

[35]Palacios-GonzálezB, Ramírez-SalazarEG, Rivera-ParedezB, et al., 2020. A multi-omic analysis for low bone mineral density in postmenopausal women suggests a relationship between diet, metabolites, and microbiota. Microorganisms, 8(11):1630.

[36]RaviA, AvershinaE, AngellIL, et al., 2018. Comparison of reduced metagenome and 16S rRNA gene sequencing for determination of genetic diversity and mother-child overlap of the gut associated microbiota. J Microbiol Methods, 149:44-52.

[37]RettedalEA, Ilesanmi-OyelereBL, RoyNC, et al., 2021. The gut microbiome is altered in postmenopausal women with osteoporosis and osteopenia. JBMR Plus, 5(3):e10452.

[38]ReyFE, FaithJJ, BainJ, et al., 2010. Dissecting the in vivo metabolic potential of two human gut acetogens. J Biol Chem, 285(29):22082-22090.

[39]RinaldiE, ConsonniA, CordiglieriC, et al., 2019. Therapeutic effect of bifidobacterium administration on experimental autoimmune myasthenia gravis in Lewis rats. Front Immunol, 10:2949.

[40]SalariN, GhasemiH, MohammadiL, et al., 2021. The global prevalence of osteoporosis in the world: a comprehensive systematic review and meta-analysis. J Orthop Surg Res, 16:609.

[41]ShiHL, YuYH, LinDH, et al., 2020. β-Glucan attenuates cognitive impairment via the gut-brain axis in diet-induced obese mice. Microbiome, 8:143.

[42]SjögrenK, EngdahlC, HenningP, et al., 2012. The gut microbiota regulates bone mass in mice. J Bone Miner Res, 27(6):1357-1367.

[43]SmetsW, LeffJW, BradfordMA, et al., 2016. A method for simultaneous measurement of soil bacterial abundances and community composition via 16S rRNA gene sequencing. Soil Biol Biochem, 96:145-151.

[44]StroupDF, BerlinJA, MortonSC, et al., 2000. Meta-analysis of observational studies in epidemiology: a proposal for reporting. JAMA, 283(15):2008-2012.

[45]SuzukiTA, LeyRE, 2020. The role of the microbiota in human genetic adaptation. Science, 370(6521):eaaz6827.

[46]TakimotoT, HatanakaM, HoshinoT, et al., 2018. Effect of Bacillus subtilis C-3102 on bone mineral density in healthy postmenopausal Japanese women: a randomized, placebo-controlled, double-blind clinical trial. Biosci Microbiota Food Health, 37(4):87-96.

[47]TettA, PasolliE, MasettiG, et al., 2021. Prevotella diversity, niches and interactions with the human host. Nat Rev Microbiol, 19(9):585-599.

[48]TousenY, MatsumotoY, NagahataY, et al., 2019. Resistant starch attenuates bone loss in ovariectomised mice by regulating the intestinal microbiota and bone-marrow inflammation. Nutrients, 11(2):297.

[49]TyagiAM, YuMC, DarbyTM, et al., 2018. The microbial metabolite butyrate stimulates bone formation via T regulatory cell-mediated regulation of WNT10B expression. Immunity, 49(6):1116-1131.e7.

[50]VangayP, JohnsonAJ, WardTL, et al., 2018. US immigration westernizes the human gut microbiome. Cell, 175(4):962-972.e10.

[51]WanXY, EguchiA, FujitaY, et al., 2022. Effects of (R)-ketamine on reduced bone mineral density in ovariectomized mice: a role of gut microbiota. Neuropharmacology, 213:109139.

[52]WangBK, ZhouYH, MaoYL, et al., 2021. Dietary supplementation with Lactobacillus plantarum ameliorates compromise of growth performance by modulating short-chain fatty acids and intestinal dysbiosis in broilers under Clostridium perfringens challenge. Front Nutr, 8:706148.

[53]WangZX, ChenK, WuCC, et al., 2021. An emerging role of Prevotella histicola on estrogen deficiency-induced bone loss through the gut microbiota-bone axis in postmenopausal women and in ovariectomized mice. Am J Clin Nutr, 114(4):1304-1313.

[54]WeiMH, LiC, DaiY, et al., 2021. High-throughput absolute quantification sequencing revealed osteoporosis-related gut microbiota alterations in Han Chinese elderly. Front Cell Infect Microbiol, 11:630372.

[55]WeiMY, ShiS, LiangC, et al., 2019. The microbiota and microbiome in pancreatic cancer: more influential than expected. Mol Cancer, 18:97.

[56]XuL, WuZF, WangY, et al., 2021. High-throughput sequencing identifies salivary microbiota in Chinese caries-free preschool children with primary dentition. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 22(4):285-294.

[57]XuZM, XieZ, SunJG, et al., 2020. Gut microbiome reveals specific dysbiosis in primary osteoporosis. Front Cell Infect Microbiol, 10:160.

[58]YachidaS, MizutaniS, ShiromaH, et al., 2019. Metagenomic and metabolomic analyses reveal distinct stage-specific phenotypes of the gut microbiota in colorectal cancer. Nat Med, 25(6):968-976.

[59]ZhaoZH, ShiAM, WangQ, et al., 2019. High oleic acid peanut oil and extra virgin olive oil supplementation attenuate metabolic syndrome in rats by modulating the gut microbiota. Nutrients, 11(12):3005.

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