国际口腔医学杂志 ›› 2017, Vol. 44 ›› Issue (6): 628-635.doi: 10.7518/gjkq.2017.06.002

• 微生物专栏 • 上一篇    下一篇

肠道微生物调控骨代谢的研究进展

吴琪1, 刘程程2, 郑黎薇3, 李继遥1, 周学东1, 徐欣1   

  1. 1.口腔疾病研究国家重点实验室 国家口腔疾病临床医学研究中心,四川大学华西口腔医院牙体牙髓病科 成都 610041;
    2.口腔疾病研究国家重点实验室 国家口腔疾病临床医学研究中心,四川大学华西口腔医院牙周病科 成都 610041;
    3.口腔疾病研究国家重点实验室 国家口腔疾病临床医学研究中心,四川大学华西口腔医院儿童口腔科 成都 610041
  • 收稿日期:2016-12-26 修回日期:2017-07-15 出版日期:2017-11-01 发布日期:2017-11-01
  • 通讯作者: 徐欣,副教授,博士,Email:xin.xu@scu.edu.cn
  • 作者简介:吴琪,硕士,Email:893222526@qq.com
  • 基金资助:
    国家自然科学基金(81430011,81371135); 四川大学优秀青年学者基金(2015SCU04A16)

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).

摘要: 人类胃肠道内栖居着数量众多且种类繁杂的微生物群,肠道菌群稳态的维持对于宿主正常代谢活动的有序进行至关重要。随着人体微生物组研究的开展,肠道菌群变化对骨代谢活动的影响引起众多学者的关注。本文对肠道微生物与骨健康的关系、肠道微生物影响骨代谢的潜在机制以及肠道微生物对牙槽骨可能发挥的调控作用进行综述,以期为肠道微生物与骨代谢相关疾病的病因学研究以及疾病诊疗提供新的思路。

关键词: 肠道, 微生物群落, 骨代谢, 牙槽骨, 牙周炎

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

中图分类号: 

  • Q939.93
[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.
[1] 郭淑娟,刘倩,丁一. 牙周病和植体周病国际新分类简介[J]. 国际口腔医学杂志, 2019, 46(2): 125-134.
[2] 吕慧欣,杜留熠,王鹞,于维先,任静宜,顾芯铭,周延民. 炎症小体在牙周炎中的研究进展[J]. 国际口腔医学杂志, 2019, 46(2): 186-190.
[3] 聂然,郭天奇,李雪,裴婷婷,秦勤,周延民. 与牙周炎相关的组织蛋白酶研究进展[J]. 国际口腔医学杂志, 2019, 46(2): 197-202.
[4] 王鹞,吕慧欣,杜留熠,顾芯铭,任静宜,于维先,周延民. 软脑膜在外周炎症影响神经炎症过程中的作用[J]. 国际口腔医学杂志, 2019, 46(2): 223-227.
[5] 杨卓,张盛丹,刘程程,丁一. 侵袭性牙周炎唾液诊断标记物的研究进展[J]. 国际口腔医学杂志, 2019, 46(1): 55-61.
[6] 许彩薇,薛毅,吴仲寅. 骨硬化蛋白与牙周炎相关性的研究进展[J]. 国际口腔医学杂志, 2018, 45(6): 703-709.
[7] 田江雪,莫龙义,贾小玥,刘程程,徐欣. 转化生长因子β在牙周炎发生发展中的作用及其机制[J]. 国际口腔医学杂志, 2018, 45(5): 553-559.
[8] 姜懿轩,莫龙义,贾小玥,徐欣,刘程程. 植物雌激素防治牙周炎的研究进展[J]. 国际口腔医学杂志, 2018, 45(5): 571-578.
[9] 黄海霞, 兰玉燕, 张昊, 潘兰兰, 郭玲, 刘敏. 慢性牙周炎患者种植修复后种植体牙周指数及龈沟液炎性因子水平的变化研究[J]. 国际口腔医学杂志, 2018, 45(4): 396-402.
[10] 郑直, 颜世果. 疱疹病毒与牙周炎的关系[J]. 国际口腔医学杂志, 2018, 45(2): 224-227.
[11] 张鹏, 丁一, 王琪. 炎性衰老在糖尿病牙周炎中的作用机制及研究现状[J]. 国际口腔医学杂志, 2017, 44(6): 664-668.
[12] 唐秋玲, 李格格, 潘佳慧, 侯玉帛, 孟阳, 于维先. 细胞焦亡与牙龈卟啉单胞菌的关系及其在牙周病发生发展中的作用机制[J]. 国际口腔医学杂志, 2017, 44(6): 660-663.
[13] 刘双, 李纾. 表观遗传学及其调控与牙周病[J]. 国际口腔医学杂志, 2017, 44(5): 523-527.
[14] 李格格, 潘佳慧, 唐秋玲, 刘歆婵, 侯玉帛, 于维先. 牙龈素促进牙龈卟啉单胞菌免疫逃逸的机制[J]. 国际口腔医学杂志, 2017, 44(5): 519-522.
[15] 李琳, 王丹, 赵曼竹, 唐明. 慢性牙周炎与神经退行性疾病相关性的研究进展[J]. 国际口腔医学杂志, 2017, 44(5): 514-518.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
[1] 张京剧. 青年期至中年期颅面复合体变化的头影测量研究[J]. 国际口腔医学杂志, 1999, 26(06): .
[2] 刘玲. 镍铬合金中铍对可铸造性和陶瓷金属结合力的影响[J]. 国际口腔医学杂志, 1999, 26(06): .
[3] 王昆润. 在种植体上制作固定义齿以后下颌骨密度的动态变化[J]. 国际口腔医学杂志, 1999, 26(06): .
[4] 王昆润. 修补颌骨缺损的新型生物学相容材料[J]. 国际口腔医学杂志, 1999, 26(06): .
[5] 汤庆奋,王学侠. 17β-雌二醇对人类阴道和口腔颊粘膜的渗透性[J]. 国际口腔医学杂志, 1999, 26(06): .
[6] 王昆润. 咀嚼口香糖对牙周组织微循环的影响[J]. 国际口腔医学杂志, 1999, 26(06): .
[7] 宋红. 青少年牙周炎外周血分叶核粒细胞的趋化功能[J]. 国际口腔医学杂志, 1999, 26(06): .
[8] 高卫民,李幸红. 发达国家牙医学院口腔种植学教学现状[J]. 国际口腔医学杂志, 1999, 26(06): .
[9] 张新春. 桩冠修复与无髓牙的保护[J]. 国际口腔医学杂志, 1999, 26(06): .
[10] 逄键梁. 两例外胚层发育不良儿童骨内植入种植体后牙槽骨生长情况[J]. 国际口腔医学杂志, 1999, 26(05): .