Inter J Stomatol ›› 2017, Vol. 44 ›› Issue (6): 628-635.doi: 10.7518/gjkq.2017.06.002

• Microbiology • Previous Articles     Next Articles

Research progress on gut microbiota regulating bone metabolism

Wu Qi1, Liu Chengcheng2, Zheng Liwei3, Li Jiyao1, Zhou Xuedong1, Xu Xin1   

  1. 1. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Conservative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China;
    2. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China;
    3. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
  • Received:2016-12-26 Revised:2017-07-15 Online:2017-11-01 Published:2017-11-01
  • Supported by:
    This study was supported by National Natural Science Foundation of China(81430011, 81371135) and Scientific Research Foundation for Young Investigators, Sichuan University, China(2015SCU04A16).

Abstract: Heterogeneous microbiota dwells in the human gastrointestinal tract, and the maintenance of gut microbiota homeostasis plays an important role in normal host metabolism. With advancement in studies on human microbial communities, the effects of gut microbiota on bone metabolism have been extensively investigated. This review summarizes the research progress on the association between gut microbiome and bone metabolism and focuses on the relationship between gut microbiota and bone fitness, the potential mechanisms of mutual interactions, and the relationship between intestinal microbiota and alveolar bones. Research advancement in this field not only enhances our understanding of the etiological role of gut microbiota in bone metabolism-related diseases but also possibly provides a novel approach for the management of bone diseases involving the microbiota.

Key words: gut, microbiota, bone metabolism, alveolar bone, periodontitis

CLC Number: 

  • Q939.93

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[1] Methe BA, Nelson KE, Pop M, et al. A framework for human microbiome research[J]. Nature, 2012, 486(742):215-221.
[2] Human Microbiome Project Consortium. Structure, function and diversity of the healthy human micro-biome[J]. Nature, 2012, 486(742):207-214.
[3] Zmora N, Zeevi D, Korem T, et al. Taking it per-sonally: personalized utilization of the human micro-biome in health and disease[J]. Cell Host Microbe, 2016, 19(1):12-20.
[4] O’toole PW, Jeffery IB. Gut microbiota and aging[J]. Science, 2015, 350(6265):1214-1215.
[5] Olszak T, An D, Zeissig S, et al. Microbial exposure during early life has persistent effects on natural killer T cell function[J]. Science, 2012, 336(680): 489-493.
[6] Wopereis H, Oozeer R, Knipping K, et al. The first thousand days—intestinal microbiology of early life: establishing a symbiosis[J]. Pediatr Allergy Immunol, 2014, 25(5):428-438.
[7] Arron JR, Choi Y. Osteoimmunology—bone versus immune system[J]. Nature, 2000, 408(6812):535- 536.
[8] Ohlsson C, Sjögren K. Effects of the gut microbiota on bone mass[J]. Trends Endocrinol Metab, 2015, 26 (2):69-74.
[9] Hooper LV, Macpherson AJ. Immune adaptations that maintain homeostasis with the intestinal micro-biota[J]. Nat Rev Immunol, 2010, 10(3):159-169.
[10] Blanton LV, Charbonneau MR, Salih T, et al. Gut bacteria that prevent growth impairments transmitted by microbiota from malnourished children[J]. Science, 2016, 351(6275):830.
[11] Black AP, Cardozo LF, Mafra D. Effects of uremic toxins from the gut microbiota on bone: a brief look at chronic kidney disease[J]. Ther Apher Dial, 2015, 19(5):436-440.
[12] Cox LM, Yamanishi S, Sohn J, et al. Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences[J]. Cell, 2014, 158(4):705-721.
[13] Cho I, Yamanishi S, Cox L, et al. Antibiotics in early life alter the murine colonic microbiome and adi-posity[J]. Nature, 2012, 488(7413):621-626.
[14] Sivan A, Corrales L, Hubert N, et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy[J]. Science, 2015, 350 (6264):1084-1089.
[15] Sjögren K, Engdahl C, Henning P, et al. The gut microbiota regulates bone mass in mice[J]. J Bone Miner Res, 2012, 27(6):1357-1367.
[16] Ivanov II, Atarashi K, Manel N, et al. Induction of intestinal Th17 cells by segmented filamentous bac-teria[J]. Cell, 2009, 139(3):485-498.
[17] Adamopoulos IE, Chao CC, Geissler R, et al. Inter-leukin-17a upregulates receptor activator of NF-kappaB on osteoclast precursors[J]. Arthritis Res Ther, 2010, 12(1):R29.
[18] Sato K, Suematsu A, Okamoto K, et al. Th17 func-tions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction[J]. J Exp Med, 2006, 203(12):2673-2682.
[19] Guerrini MM, Takayanagi H. The immune system, bone and RANKL[J]. Arch Biochem Biophys, 2014, 561(SI):118-123.
[20] Gaboriau-Routhiau V, Rakotobe S, Lécuyer E, et al. The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell re-sponses[J]. Immunity, 2009, 31(4):677-689.
[21] 周隆, 付勤. 干扰素与骨质疏松关系的研究进展[J]. 中国骨质疏松杂志, 2015, 21(11):1397-1401.
Zhou L, Fu Q. Research progress in the relationship between interferons and osteoporosis[J]. Chin J Os-teoporosis, 2015, 21(11):1397-1401.
[22] Kelchtermans H, Geboes L, Mitera T, et al. Activa-ted CD4 + CD25 + regulatory T cells inhibit osteoclas-togenesis and collagen-induced arthritis[J]. Ann Rheum Dis, 2009, 68(5):744-750.
[23] Atarashi K, Tanoue T, Shima T, et al. Induction of colonic regulatory T cells by indigenous clostridium species[J]. Science, 2011, 331(615):337-341.
[24] Bäckhed F, Ding H, Wang T, et al. The gut micro-biota as an environmental factor that regulates fat storage[J]. Proc Natl Acad Sci U S A, 2004, 101 (44):15718-15723.
[25] Chevalier C, Stojanović O, Colin DJ, et al. Gut mi-crobiota orchestrates energy homeostasis during cold [J]. Cell, 2015, 163(6):1360-1374.
[26] Lafage Proust MH. How the gut affects bone me-tabolism[J]. Joint Bone Spine, 2017, doi:10.1016/j.jbspin.2016.12.015.
[27] Parvaneh K, Jamaluddin R, Karimi G, et al. Effect of probiotics supplementation on bone mineral content and bone mass density[J]. Sci World J, 2014, doi:10.1155/2014/595962.
[28] Ohlsson C, Engdahl C, Fak F, et al. Probiotics protect mice from ovariectomy-induced cortical bone loss[J]. PLoS One, 2014, 9(3):e92368.
[29] Li JY, Chassaing B, Tyagi AM, et al. Sex steroid deficiency-associated bone loss is microbiota de-pendent and prevented by probiotics[J]. J Clin Invest, 2016, 126(6):2049-2063.
[30] Chiang SS, Pan TM. Antiosteoporotic effects of Lactobacillus -fermented soy skim milk on bone mineral density and the microstructure of femoral bone in ovariectomized mice[J]. J Agric Food Chem, 2011, 59(14):7734-7742.
[31] ( Bifidobacterium longum ) increase bone mass den-sity and upregulate sparc and Bmp-2 genes in rats with bone loss resulting from ovariectomy[J]. Biomed Res Int, 2015, doi:10.1155/2015/897639.
[32] Giustina A, Mazziotti G, Canalis E. Growth hor-mone, insulin-like growth factors, and the skeleton [J]. Endocr Rev, 2008, 29(5):535-559.
[33] Çeliker R, Arslan S. Comparison of serum insulin-like growth factor-1 and growth hormone levels in osteoporotic and non-osteoporotic postmenopausal women[J]. Rheumatol Int, 2000, 19(6):205-208.
[34] Pennisi E. Microbiome. The right gut microbes help infants grow[J]. Science, 2016, 351(6275):802.
[35] Yan J, Herzog JW, Tsang K, et al. Gut microbiota induce IGF-1 and promote bone formation and grow-th[J]. Proc Natl Acad Sci U S A, 2016, 113(47):E7554-E7563.
[36] Schieber AM, Lee YM, Chang MW, et al. Disease tolerance mediated by microbiome E. coli involves inflammasome and IGF-1 signaling[J]. Science, 2015, 350(6260):558-563.
[37] Clarke G, Stilling RM, Kennedy PJ, et al. Minireview: gut microbiota: the neglected endocrine organ[J]. Mol Endocrinol, 2014, 28(8):1221-1238.
[38] Markle JG, Frank DN, Mortin-Toth SA, et al. Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity[J]. Science, 2013, 339(6123):1084-1088.
[39] Vanderschueren D, Bouillon R. Androgens and bone [J]. Calcif Tissue Int, 1995, 56(5):341-346.
[40] Van De Wiele T, Vanhaecke L, Boeckaert C, et al. Human colon microbiota transform polycyclic aro-matic hydrocarbons to estrogenic metabolites[J]. Environ Health Perspect, 2005, 113(1):6-10.
[41] Tai V, Leung W, Grey A, et al. Calcium intake and bone mineral density: systematic review and meta-analysis[J]. BMJ, 2015, 351:h4183.
[42] Mccabe L, Britton RA, Parameswaran N. Prebiotic and probiotic regulation of bone health: role of the intestine and its microbiome[J]. Curr Osteoporos Rep, 2015, 13(6):363-371.
[43] Chaplin A, Parra P, Laraichi S, et al. Calcium sup-plementation modulates gut microbiota in a prebiotic manner in dietary obese mice[J]. Mol Nutr Food Res, 2016, 60(2):468-480.
[44] Astbury S, Mostyn A, Symonds ME, et al. Nutrient availability, the microbiome, and intestinal transport during pregnancy[J]. Appl Physiol Nutr Metab, 2015, 40(11):1100-1106.
[45] Ooi JH, Li Y, Rogers CJ, et al. Vitamin D regulates the gut microbiome and protects mice from dextran sodium sulfate-induced colitis[J]. J Nutr, 2013, 143 (10):1679-1686.
[46] Ridaura V, Belkaid Y. Gut microbiota: the link to your second brain[J]. Cell, 2015, 161(2):193-194.
[47] Yadav VK, Ryu JH, Suda N, et al. Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum[J]. Cell, 2008, 135(5):825-837.
[48] Reigstad CS, Salmonson CE, Rainey JF, et al. Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on en-terochromaffin cells[J]. FASEB J, 2015, 29(4):1395- 1403.
[49] Roberfroid M, Gibson GR, Hoyles L, et al. Prebiotic effects: metabolic and health benefits[J]. Br J Nutr, 2010, 104(Suppl 2):S1-S63.
[50] Lee SU, In HJ, Kwon MS, et al. β-Arrestin 2 me-diates G protein-coupled receptor 43 signals to nuclear factor-κB[J]. Biol Pharm Bull, 2013, 36(11): 1754-1759.
[51] Cassidy A, Brown JE, Hawdon A, et al. Factors affecting the bioavailability of soy isoflavones in humans after ingestion of physiologically relevant levels from different soy foods[J]. J Nutr, 2006, 136 (1):45-51.
[52] Landete JM, Arqués J, Medina M, et al. Bioactiva-tion of phytoestrogens: intestinal bacteria and health [J]. Crit Rev Food Sci Nutr, 2016, 56(11):1826-1843.
[53] 李海东, 蒋雷生, 戴力扬. 雌激素在骨关节炎及骨质疏松中的作用研究[J]. 中国矫形外科杂志, 2010, 18(6):474-478.
Li HD, Jiang LS, Dai LY. Role of estrogen in the development of osteoarthritis and osteoporosis[J]. Orthop J Chin, 2010, 18(6):474-478.
[54] Tousen Y, Ishiwata H, Ishimi Y, et al. Equol, a me-tabolite of daidzein, is more efficient than daidzein for bone formation in growing female rats[J]. Phytother Res, 2015, doi:10.1002/ptr.5387.
[55] Wang J, Xu J, Wang B, et al. Equol promotes rat osteoblast proliferation and differentiation through activating estrogen receptor[J]. Genet Mol Res, 2014, 13(3):5055-5063.
[56] Maekawa T, Hajishengallis G. Topical treatment with probiotic Lactobacillus brevis CD2 inhibits experimental periodontal inflammation and bone loss[J]. J Periodontal Res, 2014, 49(6):785-791.
[57] Grishin A, Bowling J, Bell B, et al. Roles of nitric oxide and intestinal microbiota in the pathogenesis of necrotizing enterocolitis[J]. J Pediatr Surg, 2016, 51(1):13-17.
[58] Tomofuji T, Ekuni D, Azuma T, et al. Supplementa-tion of broccoli or Bifidobacterium longum -fer-mented broccoli suppresses serum lipid peroxidation and osteoclast differentiation on alveolar bone surface in rats fed a high-cholesterol diet[J]. Nutrition Research, 2012, 32(4):301-307.
[59] 庞洁, 周娜, 刘鹏, 等. 罗伊氏乳杆菌的益生功能[J]. 中国生物工程杂志, 2011, 31(5):131-137.
Pang J, Zhou N, Liu P, et al. Beneficial effects of Lactobacillus reuteri to human and animals[J]. Chin Biotechnol, 2011, 31(5):131-137.
[60] Mangiapane E, Lamberti C, Pessione A, et al. Se-lenium effects on the metabolism of a Se-metabo-lizing Lactobacillus reuteri : analysis of envelope-enriched and extracellular proteomes[J]. Mol Biosyst, 2014, 10(6):1272-1280.
[61] Delilbasi C, Demiralp S, Turan B. Effects of selenium on the structure of the mandible in experimental diabetics[J]. J Oral Sci, 2002, 44(2):85-90.
[62] 刘文婷. 肠道柔嫩梭菌与牙周健康相关性研究[D]. 济南: 山东大学, 2013.
Liu WT. Correlation between intestinal Clostridium leptum and periodontal health[D]. Jinan: Shandong University, 2013.
[63] O’Mahony C, Scully P, O’Mahony D, et al. Com-mensal-induced regulatory T cells mediate protection against pathogen-stimulated NF-kappaB activation [J]. PLoS Pathog, 2008, 4(8):e1000112.
[64] Britton RA, Irwin R, Quach D, et al. Probiotic L. reuteri treatment prevents bone loss in a menopausal ovariectomized mouse model[J]. J Cell Physiol, 2014, 229(11):1822-1830.
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[6] . [J]. Foreign Med Sci: Stomatol, 1999, 26(04): .
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[9] . [J]. Inter J Stomatol, 2008, 35(S1): .
[10] . [J]. Inter J Stomatol, 2008, 35(S1): .