国际口腔医学杂志 ›› 2017, Vol. 44 ›› Issue (6): 619-627.doi: 10.7518/gjkq.2017.06.001

• 专家论坛 •    下一篇

口腔微生物组在口腔精准医疗中的运用

徐欣, 何金枝, 周学东   

  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
  • 收稿日期:2017-06-09 修回日期:2017-07-13 出版日期:2017-11-01 发布日期:2017-11-01
  • 通讯作者: 周学东,教授,博士,Email:zhouxd@scu.edu.cn
  • 作者简介:徐欣,副教授,博士,Email:xin.xu@scu.edu.cn
  • 基金资助:
    国家自然科学基金(81670978,81600874); 四川省科技厅重大前沿项目(2016JY0006); 四川大学华西口腔医院临床新技术项目(LCXJS2015-3)

Oral microbiome in the precision medicine

Xu Xin, He Jinzhi, Zhou Xuedong.   

  1. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Conservative Dentistry and Endodontis, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
  • Received:2017-06-09 Revised:2017-07-13 Online:2017-11-01 Published:2017-11-01
  • Supported by:
    This study was supported by National Natural Science Foundation of China(81670978, 81600874), Key Project for Frontier Research of Science and Technology Department of Sichuan Province(2016JY0006), and Clinical Innovation Grant of West China Hospital of Stomatology, Sichuan University(LCXJS2015-3).

摘要: 现代医学已从“以疾病为导向”转至“以患者为导向”,开启了以个体化医疗为目标的精准医疗时代。人体的生理功能不但由自身基因组决定,还受共生菌群即人类微生物组的塑造与影响。目前,人类微生物组的研究已经超越了简单解析组成成员与疾病之间的相关性,开始深入分析其对复杂疾病发病、诊断及治疗的贡献,这些突破性研究成果有望成为推动个性化精准医疗的重要助力。本文着重介绍口腔微生物组的最新研究进展、口腔微生物组在疾病早期风险预警、早期诊断、治疗及疗效评估等方面的探索性运用,讨论了口腔微生物组在精准医疗发展中的潜力,以及整合口腔微生物组信息,实现精准医疗所面临的重大挑战。

关键词: 口腔微生物组, 精准医疗, 组学研究, 精准预警, 精准诊断, 精准治疗, 精准疗效评估

Abstract: Modern medicine has shifted from “disease oriented” to “patient oriented” and has consequently created a new era of personalized medicine or precision medicine. The physiological functions of the human body are determined not only by the human genome but also by symbiotic microflora. Currently, studies on the human microbiome have extended from a simple analysis of the association of bacteria and diseases to a complex analysis of the role of microbiome in the pathogenesis, diagnosis, and treatment of diseases. These breakthroughs possibly promote the practice of personalized/precision medicine. This review summarizes the advances in oral microbiome-related research. In particular, the potential role of oral microbiome in the risk prediction, diagnosis, treatment evaluation, and prognosis of diseases is extensively discussed. Current challenges in the development of oral microbiome-based precision medicine are also described.

Key words: oral microbiome, precision medicine, omics, precise risk prediction, precise diagnosis, precise therapy, precise evaluation

中图分类号: 

  • R37
[1] Bayer R, Galea S. Public health in the precision-medicine era[J]. N Engl J Med, 2015, 373(6):499- 501.
[2] Jameson JL, Longo DL. Precision medicine—per-sonalized, problematic, and promising[J]. N Engl J Med, 2015, 372(23):2229-2234.
[3] Ashley EA. The precision medicine initiative: a new national effort[J]. JAMA, 2015, 313(21):2119-2120.
[4] Collins FS, Varmus H. A new initiative on precision medicine[J]. N Engl J Med, 2015, 372(9):793-795.
[5] Turnbaugh PJ, Ley RE, Mahowald MA, et al. An obesity-associated gut microbiome with increased capacity for energy harvest[J]. Nature, 2006, 444 (7122):1027-1031.
[6] Suez J, Korem T, Zeevi D, et al. Artificial sweeteners induce glucose intolerance by altering the gut micro-biota[J]. Nature, 2014, 514(7521):181-186.
[7] Qin J, Li Y, Cai Z, et al. A metagenome-wide asso-ciation study of gut microbiota in type 2 diabetes[J]. Nature, 2012, 490(7418):55-60.
[8] Claesson MJ, Jeffery IB, Conde S, et al. Gut micro-biota composition correlates with diet and health in the elderly[J]. Nature, 2012, 488(7410):178-184.
[9] Dewhirst FE, Chen T, Izard J, et al. The human oral microbiome[J]. J Bacteriol, 2010, 192(19):5002- 5017.
[10] Wade WG. The oral microbiome in health and disease[J]. Pharmacol Res, 2013, 69(1):137-143.
[11] He J, Li Y, Cao Y, et al. The oral microbiome diversity and its relation to human diseases[J]. Folia Microbiol(Praha), 2015, 60(1):69-80.
[12] Riviere GR, Riviere KH, Smith KS. Molecular and immunological evidence of oral Treponema in the human brain and their association with Alzheimer’s disease[J]. Oral Microbiol Immunol, 2002, 17(2): 113-118.
[13] Zhou M, Rong R, Munro D, et al. Investigation of the effect of type 2 diabetes mellitus on subgingival plaque microbiota by high-throughput 16S rDNA pyrosequencing[J]. PLoS One, 2013, 8(4):e61516.
[14] Mendz GL, Kaakoush NO, Quinlivan JA. Bacterial aetiological agents of intra-amniotic infections and preterm birth in pregnant women[J]. Front Cell In-fect Microb, 2013, 3:58.
[15] Zhang Z, Zhai H, Geng J, et al. Large-scale survey of gut microbiota associated with MHE via 16S rRNA-based pyrosequencing[J]. Am J Gastroenterol, 2013, 108(10):1601-1611.
[16] Fåk F, Tremaroli V, Bergström G, et al. Oral micro-biota in patients with atherosclerosis[J]. Atheroscle-rosis, 2015, 243(2):573-578.
[17] Gonzalez A, Hyde E, Sangwan N, et al. Migraines are correlated with higher levels of nitrate-, nitrite-, and nitric oxide-reducing oral microbes in the Ame-rican gut project cohort[J]. mSystems, 2016, 1(5):e00105-16.
[18] Chen T, Wen HY, Izard J, et al. The human oral microbiome database: a web accessible resource for investigating oral microbe taxonomic and genomic information[J]. Database(Oxford), 2010, 2010:baq- 013.
[19] Gizani S, Papaioannou W, Haffajee AD, et al. Distri-bution of selected cariogenic bacteria in five different intra—oral habitats in young children[J]. Int J Pae-diatr Dent, 2009, 19(3):193-200.
[20] Huse SM, Ye Y, Zhou Y, et al. A core human micro-biome as viewed through 16S rRNA sequence clus-ters[J]. PLoS One, 2012, 7(6):e34242.
[21] Xu X, He J, Xue J, et al. Oral cavity contains distinct niches with dynamic microbial communities[J]. Environ Microbiol, 2015, 17(3):699-710.
[22] Nasidze I, Li J, Quinque D, et al. Global diversity in the human salivary microbiome[J]. Genome Res, 2009, 19(4):636-643.
[23] Lazarevic V, Whiteson K, Hernandez D, et al. Study of inter- and intra-individual variations in the salivary microbiota[J]. BMC Genomics, 2010, 11:523.
[24] 杜芹, 王艳, 徐欣, 等. 双生子儿童口腔微生物群组结构分析[J]. 华西口腔医学杂志, 2014, 32(2):182- 185.
Du Q, Wang Y, Xu X, et al. Analysis of the oral microbiota in twin children[J]. West China J Sto-matol, 2014, 32(2):182-185.
[25] Luo AH, Yang DQ, Xin BC, et al. Microbial profiles in saliva from children with and without caries in mixed dentition[J]. Oral Dis, 2012, 18(6):595-601.
[26] Papapostolou A, Kroffke B, Tatakis DN, et al. Con-tribution of host genotype to the composition of health-associated supragingival and subgingival microbiomes[J]. J Clin Periodontol, 2011, 38(6):517- 524.
[27] Teng F, Yang F, Huang S, et al. Prediction of early childhood caries via spatial-temporal variations of oral microbiota[J]. Cell Host Microbe, 2015, 18(3): 296-306.
[28] Yang F, Zeng X, Ning K, et al. Saliva microbiomes distinguish caries-active from healthy human popula-tions[J]. ISME J, 2012, 6(1):1-10.
[29] Huang S, Yang F, Zeng X, et al. Preliminary charac-terization of the oral microbiota of Chinese adults with and without gingivitis[J]. BMC Oral Health, 2011, 11(1):33.
[30] Li Y, He J, He Z, et al. Phylogenetic and functional gene structure shifts of the oral microbiomes in periodontitis patients[J]. ISME J, 2014, 8(9):1879- 1891.
[31] Alves FR, Siqueira JF Jr, Carmo FL, et al. Bacterial community profiling of cryogenically ground sam-ples from the apical and coronal root segments of teeth with apical periodontitis[J]. J Endod, 2009, 35(4):486-492.
[32] Rôças IN, Alves FRF, Santos AL, et al. Apical root canal microbiota as determined by reverse-capture checkerboard analysis of cryogenically ground root samples from teeth with apical periodontitis[J]. J Endod, 2010, 36(10):1617-1621.
[33] Kazor CE, Mitchell PM, Lee AM, et al. Diversity of bacterial populations on the tongue dorsa of patients with halitosis and healthy patients[J]. J Clin Micro-biol, 2003, 41(2):558-563.
[34] Wang K, Miao T, Lu W, et al. Analysis of oral micro-bial community and Th17-associated cytokines in saliva of patients with oral lichen planus[J]. Micro-biol Immunol, 2015, 59(3):105-113.
[35] Mager DL, Haffajee AD, Devlin PM, et al. The salivary microbiota as a diagnostic indicator of oral cancer: a descriptive, non-randomized study of cancer-free and oral squamous cell carcinoma sub-jects[J]. J Transl Med, 2005, 3(1):27.
[36] Ling Z, Kong J, Jia P, et al. Analysis of oral micro-biota in children with dental caries by PCR-DGGE and barcoded pyrosequencing[J]. Microb Ecol, 2010, 60(3):677-690.
[37] Tanner AC, Kent RL Jr, Holgerson PL, et al. Micro-biota of severe early childhood caries before and after therapy[J]. J Dent Res, 2011, 90(11):1298- 1305.
[38] Preza D, Olsen I, Aas JA, et al. Bacterial profiles of root caries in elderly patients[J]. J Clin Microbiol, 2008, 46(6):2015-2021.
[39] Aas JA, Griffen AL, Dardis SR, et al. Bacteria of dental caries in primary and permanent teeth in children and young adults[J]. J Clin Microbiol, 2008, 46(4):1407-1417.
[40] Belda-Ferre P, Alcaraz LD, Cabrera-Rubio R, et al. The oral metagenome in health and disease[J]. ISME J, 2012, 6(1):46-56.
[41] Colombo AP, Boches SK, Cotton SL, et al. Com-parisons of subgingival microbial profiles of refrac-tory periodontitis, severe periodontitis, and periodon-tal health using the human oral microbe identifica-tion microarray[J]. J Periodontol, 2009, 80(9):1421- 1432.
[42] Colombo AP, Bennet S, Cotton SL, et al. Impact of periodontal therapy on the subgingival microbiota of severe periodontitis: comparison between good re-sponders and individuals with refractory periodon-titis using the human oral microbe identification microarray[J]. J Periodontol, 2012, 83(10):1279- 1287.
[43] Shchipkova AY, Nagaraja HN, Kumar PS. Subgin-gival microbial profiles of smokers with periodontitis [J]. J Dent Res, 2010, 89(11):1247-1253.
[44] Griffen AL, Beall CJ, Campbell JH, et al. Distinct and complex bacterial profiles in human periodon-titis and health revealed by 16S pyrosequencing[J]. ISME J, 2012, 6(6):1176-1185.
[45] Heuer W, Kettenring A, Stumpp S, et al. Metagenomic analysis of the peri-implant and periodontal micro-flora in patients with clinical signs of gingivitis or mucositis[J]. Clin Oral Investig, 2012, 16(3):843- 850.
[46] Siqueira JF Jr, Alves FR, Rôças IN. Pyrosequencing analysis of the apical root canal microbiota[J]. J Endod, 2011, 37(11):1499-1503.
[47] Santos AL, Siqueira JF Jr, Rôças IN, et al. Com-paring the bacterial diversity of acute and chronic dental root canal infections[J]. PLoS One, 2011, 6 (11):e28088.
[48] Li L, Hsiao WW, Nandakumar R, et al. Analyzing endodontic infections by deep coverage pyrose-quencing[J]. J Dent Res, 2010, 89(9):980-984.
[49] Rôças IN, Siqueira JF Jr, Debelian GJ. Analysis of symptomatic and asymptomatic primary root canal infections in adult Norwegian patients[J]. J Endod, 2011, 37(9):1206-1212.
[50] Munson MA, Pitt-Ford T, Chong B, et al. Molecular and cultural analysis of the microflora associated with endodontic infections[J]. J Dent Res, 2002, 81 (11):761-766.
[51] Vickerman MM, Brossard KA, Funk DB, et al. Phy-logenetic analysis of bacterial and archaeal species in symptomatic and asymptomatic endodontic infec-tions[J]. J Med Microbiol, 2007, 56(1):110-118.
[52] Porter SR, Scully C. Oral malodour(halitosis)[J]. BMJ, 2006, 333(7569):632-635.
[53] Allaker RP, Waite RD, Hickling J, et al. Topographic distribution of bacteria associated with oral malodour on the tongue[J]. Arch Oral Biol, 2008, 53(Suppl):S8-S12.
[54] Montagner F, Gomes BP, Kumar PS. Molecular fingerprinting reveals the presence of unique com-munities associated with paired samples of root canals and acute apical abscesses[J]. J Endod, 2010, 36(9): 1475-1479.
[55] Ford PJ, Gemmell E, Hamlet SM, et al. Cross-reac-tivity of GroEL antibodies with human heat shock protein 60 and quantification of pathogens in athero-sclerosis[J]. Oral Microbiol Immunol, 2005, 20(5): 296-302.
[56] Figuero E, Sánchez-Beltrán M, Cuesta-Frechoso S, et al. Detection of periodontal bacteria in atheroma-tous plaque by nested polymerase chain reaction[J]. J Periodontol, 2011, 82(10):1469-1477.
[57] Pucar A, Milasin J, Lekovic V, et al. Correlation between atherosclerosis and periodontal putative pathogenic bacterial infections in coronary and in-ternal mammary arteries[J]. J Periodontol, 2007, 78 (4):677-682.
[58] Guinane CM, Tadrous A, Fouhy F, et al. Microbial composition of human appendices from patients fol-lowing appendectomy[J]. MBio, 2013, 4(1):e00366- 12.
[59] Farrell JJ, Zhang L, Zhou H, et al. Variations of oral microbiota are associated with pancreatic diseases including pancreatic cancer[J]. Gut, 2011, 61(4):582- 588.
[60] Fardini Y, Chung P, Dumm R, et al. Transmission of diverse oral bacteria to murine placenta: evidence for the oral microbiome as a potential source of intrau-terine infection[J]. Infect Immun, 2010, 78(4): 1789-1796.
[61] Casarin R, Barbagallo A, Meulman T, et al. Subgin-gival biodiversity in subjects with uncontrolled type- 2 diabetes and chronic periodontitis[J]. J Periodontal Res, 2013, 48(1):30-36.
[62] Zhang X, Zhang D, Jia H, et al. The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment[J]. Nat Med, 2015, 21(8):895-905.
[63] Koren O, Spor A, Felin J, et al. Microbes and Health Sackler Colloquium: human oral, gut, and plaque microbiota in patients with atherosclerosis[J]. Proc Natl Acad Sci U S A, 2011, 108(Suppl 1):4592- 4598.
[64] de Pablo P, Chapple IL, Buckley CD, et al. Perio-dontitis in systemic rheumatic diseases[J]. Nat Rev Rheumatol, 2009, 5(4):218-224.
[65] Han YW, Fardini Y, Chen C, et al. Term stillbirth caused by oral Fusobacterium nucleatum [J]. Obstet Gynecol, 2010, 115(2 Pt 2):442-445.
[66] Huang S, Li R, Zeng X, et al. Predictive modeling of gingivitis severity and susceptibility via oral micro-biota[J]. ISME J, 2014, 8(9):1768-1780.
[67] Huang S, Li Z, He T, et al. Microbiota-based signa-ture of gingivitis treatments: a randomized study[J]. Sci Rep, 2016, 6:24705.
[68] Simón-Soro A, Belda-Ferre P, Cabrera-Rubio R, et al. A tissue-dependent hypothesis of dental caries[J]. Caries Res, 2013, 47(6):591-600.
[69] Duran-Pinedo AE, Chen T, Teles R, et al. Community-wide transcriptome of the oral microbiome in sub-jects with and without periodontitis[J]. ISME J, 2014, 8(8):1659-1672.
[70] Jorth P, Turner KH, Gumus P, et al. Metatranscrip-tomics of the human oral microbiome during health and disease[J]. MBio, 2014, 5(2):e01012-14.
[71] Peterson SN, Meissner T, Su AI, et al. Functional expression of dental plaque microbiota[J]. Front Cell Infect Microbiol, 2014, 4:108.
[72] Frias-Lopez J, Duran-Pinedo A. Effect of periodontal pathogens on the metatranscriptome of a gealthy multispecies biofilm model[J]. J Bacteriol, 2012, 194(8):2082-2095.
[73] Schwanhäusser B, Busse D, Li N, et al. Global quan-tification of mammalian gene expression control[J]. Nature, 2011, 473(7347):337-342.
[74] Jagtap P, McGowan T, Bandhakavi S, et al. Deep metaproteomic analysis of human salivary superna-tant[J]. Proteomics, 2012, 12(7):992-1001.
[75] Belda-Ferre P, Williamsón J, Simon-SoroÁ, et al. The human oral metaproteome reveals potential biomarkers for caries disease[J]. Proteomics, 2015, 15(20):3497-3507.
[76] Bostanci N, Heywood W, Mills K, et al. Application of label-free absolute quantitative proteomics in human gingival crevicular fluid by LC/MS E(gin-gival exudatome)[J]. J Proteome Res, 2010, 9(5): 2191-2199.
[77] Grant MM, Creese AJ, Barr G, et al. Proteomic analysis of a noninvasive human model of acute inflammation and its resolution: the twenty-one day gingivitis model[J]. J Proteome Res, 2010, 9(9): 4732-4744.
[78] Takahashi N, Washio J, Mayanagi G. Metabolomics of supragingival plaque and oral bacteria[J]. J Dent Res, 2010, 89(12):1383-1388.
[79] Barnes VM, Ciancio SG, Shibly O, et al. Metabo-lomics reveals elevated macromolecular degradation in periodontal disease[J]. J Dent Res, 2011, 90(11): 1293-1297.
[80] Listl S, Galloway J, Mossey PA, et al. Global eco-nomic impact of dental diseases[J]. J Dent Res, 2015, 94(10):1355-1361.
[81] Guo L, McLean JS, Yang Y, et al. Precision-guided antimicrobial peptide as a targeted modulator of human microbial ecology[J]. Proc Natl Acad Sci U S A, 2015, 112(24):7569-7574.
[82] Eckert R, He J, Yarbrough DK, et al. Targeted killing of Streptococcus mutans by a pheromone-guided “smart” antimicrobial peptide[J]. Antimicrob Agents Chemother, 2006, 50(11):3651-3657.
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