[go: up one dir, main page]

Skip to main content
Log in

The oral microbiome profile and biomarker in Chinese type 2 diabetes mellitus patients

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Purpose

Oral microbiota maintains a dynamic ecological balance with the host. However, a disruption in this balance can lead to oral diseases such as dental caries and periodontitis. Several studies suggest differences in microbial composition in the oral cavity between patients with T2DM and nondiabetic patients. However, there is inadequate oral microbiome-related data from Chinese patients with T2DM, and the difference in microbiome profile between Chinese patients with T2DM and other ethnicities needs to be investigated further.

Method

Oral swab samples were collected from 280 adult patients with T2DM and 162 healthy controls. Illumina sequencing was performed on oral samples targeting V1–V2 region of 16S rRNA gene and sequence analysis was carried in the QIIME.

Results

Patients with T2DM and healthy cohorts exhibited distinct oral microbial clusters based on principal coordinate analysis (PCoA). The Firmicutes/Bacteroidetes ratio increased in T2DM and T2DM patients presented significantly higher numbers of Neisseria, Streptococcus, Haemophilus, and Pseudomonas genera, and lower numbers of Acinetobacteria compared with healthy controls. When compared with the available published data of oral and gut microbiome associated with T2DM patients, we found the ratio of Firmicutes/Bacteroidetes and the abundance of Haemophilus could be a specific microbial biomarker in Chinese patients with T2DM.

Conclusions

Our study revealed a significant difference in the oral microbiota between T2DM patients and healthy individuals. We identified 25 taxa, including 6 genera, with significant difference in abundance between T2DM and healthy controls.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. N.H. Cho, J.E. Shaw, S. Karuranga, Y. Huang, R.F.J. Da, A.W. Ohlrogge, B. Malanda, IDF diabetes Atlas: global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res. Clin. Pract. 138, 271 (2018)

    Article  CAS  Google Scholar 

  2. J. Tuomilehto, The emerging global epidemic of type 1 diabetes. Curr. Diab. Rep. 13(6), 795–804 (2013). https://doi.org/10.1007/s11892-013-0433-5

    Article  CAS  PubMed  Google Scholar 

  3. M.E. Cerf, Beta cell dysfunction and insulin resistance. Front. Endocrinol. 4, 37 (2013)

  4. K.N. Keane, E.K. Calton, R. Carlessi, P.H. Hart, P. Newsholme, The bioenergetics of inflammation: insights into obesity and type 2 diabetes. Eur. J. Clin. Nutr. 71(7), 904–912 (2017)

    Article  CAS  Google Scholar 

  5. F. Llambés, S. Ariasherrera, R. Caffesse, Relationship between diabetes and periodontal infection. World J. Diabetes 6(7), 927–935 (2015)

    Article  Google Scholar 

  6. P.M. Preshaw, A.L. Alba, D. Herrera, S. Jepsen, A. Konstantinidis, K. Makrilakis, R. Taylor, Periodontitis and diabetes: a two-way relationship. Diabetologia 55(1), 21–31 (2012)

    Article  CAS  Google Scholar 

  7. R.C. Casarin, A. Barbagallo, T. Meulman, V.R. Santos, E.A. Sallum, F.H. Nociti, P.M. Duarte, M.Z. Casati, R.B. Gonçalves, Subgingival biodiversity in subjects with uncontrolled type-2 diabetes and chronic periodontitis. J. Periodontal Res. 48(1), 30–36 (2013)

    Article  CAS  Google Scholar 

  8. N. Makiura, M. Ojima, Y. Kou, N. Furuta, N. Okahashi, S. Shizukuishi, A. Amano, Relationship of Porphyromonas gingivalis with glycemic level in patients with type 2 diabetes following periodontal treatment. Oral. Microbiol. Immunol. 23(4), 348–351 (2010)

    Article  Google Scholar 

  9. F.E. Dewhirst, T. Chen, J. Izard, B.J. Paster, A.C. Tanner, W.H. Yu, A. Lakshmanan, W.G. Wade, The human oral microbiome. J. Bacteriol. 192(19), 5002 (2010)

    Article  CAS  Google Scholar 

  10. W.G. Wade, The oral microbiome in health and disease. Pharmacol. Res. 69(1), 137–143 (2013). https://doi.org/10.1016/j.phrs.2012.11.006

    Article  CAS  PubMed  Google Scholar 

  11. M. Kilian, I.L. Chapple, M. Hannig, P.D. Marsh, V. Meuric, A.M. Pedersen, M.S. Tonetti, W.G. Wade, E. Zaura, The oral microbiome—an update for oral healthcare professionals. Br. Dent. J. 221(10), 657 (2016)

  12. F. Teng, F. Yang, S. Huang, C. Bo, Z. Xu, Prediction of early childhood caries via spatial-temporal variations of oral microbiota. Cell Host Microbe 18(3), 296–306 (2015)

    Article  CAS  Google Scholar 

  13. C. Chen, C. Hemme, J. Beleno, Z.J. Shi, D. Ning, Y. Qin, Q. Tu, M. Jorgensen, Z. He, L. Wu, Oral microbiota of periodontal health and disease and their changes after nonsurgical periodontal therapy. ISME J. 12(5), 1210–1224 (2018)

    Article  Google Scholar 

  14. Y.W. Han, X. Wang, Mobile microbiome: oral bacteria in extra-oral infections and inflammation. J. Dent. Res. 92(6), 485–491 (2013)

    Article  CAS  Google Scholar 

  15. W.D. Miller, The human mouth as a focus of infection. Lancet 138(3546), 340–342 (1891)

  16. M.L. Metzker, Sequencing technologies—the next generation. Nat. Rev. Genet. 11(1), 31–46 (2010)

    Article  CAS  Google Scholar 

  17. E. Figuero, S. Cuesta-Frechoso, J.M. Tejerina, J.A. Del Castro, D. Herrera, M. Sanz, Detection of periodontal bacteria in atheromatous plaque by nested polymerase chain reaction. J. Periodontol. 82(10), 1469–1477 (2011)

    Article  CAS  Google Scholar 

  18. P.N. Madianos, Y.A. Bobetsis, S. Offenbacher, Adverse pregnancy outcomes (APOs) and periodontal disease: pathogenic mechanisms. J. Clin. Periodontol. 40(s14), S170–S180 (2013)

    PubMed  Google Scholar 

  19. J.M. Goodson, D. Groppo, S. Halem, E. Carpino, Is obesity an oral bacterial disease? J. Dent. Res. 88(6), 519–523 (2009)

    Article  CAS  Google Scholar 

  20. J.C.O. Sardi, C. Duque, G.A.C.G. Camargo, J.F. Hofling, R.B. Gonçalves, Periodontal conditions and prevalence of putative periodontopathogens and Candida spp. in insulin-dependent type 2 diabetic and non-diabetic patients with chronic periodontitis—a pilot study. Arch. Oral. Biol. 56(10), 1098–1105 (2011)

    Article  CAS  Google Scholar 

  21. R. Anbalagan, P. Srikanth, M. Mani, R. Barani, K.G. Seshadri, R. Janarthanan, Next generation sequencing of oral microbiota in type 2 diabetes mellitus prior to and after neem stick usage and correlation with serum monocyte chemoattractant-1. Diabetes Res. Clin. Pract. 130, 204 (2017)

    Article  CAS  Google Scholar 

  22. T. Ogawa, M. Hondaogawa, K. Ikebe, Y. Notomi, Y. Iwamoto, I. Shirobayashi, S. Hata, M. Kibi, S. Masayasu, S. Sasaki, Characterizations of oral microbiota in elderly nursing home residents with diabetes. J. Oral. Sci. 60(4), 549–555 (2017)

    Article  Google Scholar 

  23. M. Zhou, R. Rong, D. Munro, C. Zhu, X. Gao, Q. Zhang, Q. Dong, Investigation of the effect of type 2 diabetes mellitus on subgingival plaque microbiota by high-throughput 16S rDNA pyrosequencing. PLoS ONE 8(4), e61516 (2013)

    Article  CAS  Google Scholar 

  24. E.J. Ohlrich, M.P. Cullinan, J.W. Leichter, Diabetes, periodontitis, and the subgingival microbiota. J. Oral. Microbiol. 2(2010), 10 (2010)

    PubMed Central  Google Scholar 

  25. F. Fouhy, A.G. Clooney, C. Stanton, M.J. Claesson, P.D. Cotter, 16S rRNA gene sequencing of mock microbial populations- impact of DNA extraction method, primer choice and sequencing platform. BMC Microbiol. 16(1), 123 (2016)

    Article  Google Scholar 

  26. T. Magoč, S.L. Salzberg, FLASH: fast length adjustment of short reads to improve genome assemblies. Bioinformatics 27(21), 2957–2963 (2011)

    Article  Google Scholar 

  27. R.C. Edgar, Search and clustering orders of magnitude faster than BLAST. Bioinformatics 26(19), 2460 (2010)

    Article  CAS  Google Scholar 

  28. J.R. Cole, Q. Wang, E. Cardenas, J. Fish, B. Chai, R.J. Farris, A.S. Kulamsyedmohideen, D.M. Mcgarrell, T. Marsh, G.M. Garrity, The Ribosomal Database Project: improved alignments and new tools for rRNA analysis. Nucleic Acids Res. 37, D141–D145 (2009)

  29. N. Segata, J. Izard, L. Waldron, D. Gevers, L. Miropolsky, W.S. Garrett, C. Huttenhower, Metagenomic biomarker discovery and explanation. Genome Biol. 12(6), R60 (2011)

    Article  Google Scholar 

  30. L. Dong, J. Yin, J. Zhao, S. Ma, H. Wang, M. Wang, W. Chen, W. Wei, Microbial similarity and preference for specific sites in healthy oral cavity and esophagus. Front. Microbiol. 9, 1603 (2018)

    Article  Google Scholar 

  31. J. Qin, Y. Li, Z. Cai, S. Li, J. Zhu, F. Zhang, S. Liang, W. Zhang, Y. Guan, D. Shen, Y. Peng, D. Zhang, Z. Jie, W. Wu, Y. Qin, W. Xue, J. Li, L. Han, D. Lu, P. Wu, Y. Dai, X. Sun, Z. Li, A. Tang, S. Zhong, X. Li, W. Chen, R. Xu, M. Wang, Q. Feng, M. Gong, J. Yu, Y. Zhang, M. Zhang, T. Hansen, G. Sanchez, J. Raes, G. Falony, S. Okuda, M. Almeida, E. LeChatelier, P. Renault, N. Pons, J.M. Batto, Z. Zhang, H. Chen, R. Yang, W. Zheng, S. Li, H. Yang, J. Wang, S.D. Ehrlich, R. Nielsen, O. Pedersen, K. Kristiansen, J. Wang, A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 490(7418), 55–60 (2012). https://doi.org/10.1038/nature11450

    Article  CAS  PubMed  Google Scholar 

  32. N. Qin, F. Yang, A. Li, E. Prifti, Y. Chen, L. Shao, J. Guo, C.E. Le, J. Yao, L. Wu, Alterations of the human gut microbiome in liver cirrhosis. Nature 513(7516), 59–64 (2014)

    Article  CAS  Google Scholar 

  33. X. Zhang, D. Zhang, H. Jia, Q. Feng, D. Wang, D. Liang, X. Wu, J. Li, L. Tang, Y. Li, Z. Lan, B. Chen, Y. Li, H. Zhong, H. Xie, Z. Jie, W. Chen, S. Tang, X. Xu, X. Wang, X. Cai, S. Liu, Y. Xia, J. Li, X. Qiao, J.Y. Al-Aama, H. Chen, L. Wang, Q.J. Wu, F. Zhang, W. Zheng, Y. Li, M. Zhang, G. Luo, W. Xue, L. Xiao, J. Li, W. Chen, X. Xu, Y. Yin, H. Yang, J. Wang, K. Kristiansen, L. Liu, T. Li, Q. Huang, Y. Li, J. Wang, The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment. Nat. Med. 21(8), 895–905 (2015). https://doi.org/10.1038/nm.3914

    Article  CAS  PubMed  Google Scholar 

  34. N. Larsen, F.K. Vogensen, F.W. van den Berg, D.S. Nielsen, A.S. Andreasen, B.K. Pedersen, W.A. Al-Soud, S.J. Sorensen, L.H. Hansen, M. Jakobsen, Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS ONE 5(2), e9085 (2010). https://doi.org/10.1371/journal.pone.0009085

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. M. Remely, E. Aumueller, D. Jahn, B. Hippe, H. Brath, A.G. Haslberger, Microbiota and epigenetic regulation of inflammatory mediators in type 2 diabetes and obesity. Benef. Microbes 5(1), 33–43 (2014)

    Article  CAS  Google Scholar 

  36. K. Forslund, F. Hildebrand, T. Nielsen, G. Falony, E. Le Chatelier, S. Sunagawa, E. Prifti, S. Vieira-Silva, V. Gudmundsdottir, H.K. Pedersen, M. Arumugam, K. Kristiansen, A.Y. Voigt, H. Vestergaard, R. Hercog, P.I. Costea, J.R. Kultima, J. Li, T. Jorgensen, F. Levenez, J. Dore, H.I.Tc Meta, H.B. Nielsen, S. Brunak, J. Raes, T. Hansen, J. Wang, S.D. Ehrlich, P. Bork, O. Pedersen, Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature 528(7581), 262–266 (2015). https://doi.org/10.1038/nature15766

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. A. Rodriguez-Hernandez, L. Marquez-Corono, A.-P. Pontigo-Loyola, L.A. Ximenez-Fyvie, Subgingival microbiota of an indigenous mexican population with chronic periodontitis and T2DM, 7(2), 00238 (2017)

  38. K. Kampoo, Bacteriological Investigations of the Human Oral Microbiota in Health and Disease, Doctoral dissertation, University of Manchester (2011)

  39. Z. Xun, Q. Zhang, T. Xu, N. Chen, F. Chen, Dysbiosis and ecotypes of the salivary microbiome associated with inflammatory bowel diseases and the assistance in diagnosis of diseases using oral bacterial profiles. Front. Microbiol. 9, 1136 (2018). https://doi.org/10.3389/fmicb.2018.01136

    Article  PubMed  PubMed Central  Google Scholar 

  40. M.Z. Afzal, R.R. Mercado, K. Shirai, Efficacy of metformin in combination with immune checkpoint inhibitors (anti-PD-1/anti-CTLA-4) in metastatic malignant melanoma. J. Immunother. Cancer 6(1), 64 (2018). https://doi.org/10.1186/s40425-018-0375-1

    Article  PubMed  PubMed Central  Google Scholar 

  41. T. Bryrup, C.W. Thomsen, T. Kern, K.H. Allin, I. Brandslund, N.R. Jorgensen, H. Vestergaard, T. Hansen, T.H. Hansen, O. Pedersen, T. Nielsen, Metformin-induced changes of the gut microbiota in healthy young men: results of a non-blinded, one-armed intervention study. Diabetologia 62(6), 1024–1035 (2019). https://doi.org/10.1007/s00125-019-4848-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. H. Wu, E. Esteve, V. Tremaroli, M.T. Khan, R. Caesar, L. Manneras-Holm, M. Stahlman, L.M. Olsson, M. Serino, M. Planas-Felix, G. Xifra, J.M. Mercader, D. Torrents, R. Burcelin, W. Ricart, R. Perkins, J.M. Fernandez-Real, F. Backhed,, Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug. Nat. Med. 23(7), 850–858 (2017). https://doi.org/10.1038/nm.4345

    Article  CAS  PubMed  Google Scholar 

  43. R. Pryor, P. Norvaisas, G. Marinos, L. Best, L.B. Thingholm, L.M. Quintaneiro, W. De Haes, D. Esser, S. Waschina, C. Lujan, R.L. Smith, T.A. Scott, D. Martinez-Martinez, O. Woodward, K. Bryson, M. Laudes, W. Lieb, R.H. Houtkooper, A. Franke, L. Temmerman, I. Bjedov, H.M. Cocheme, C. Kaleta, F. Cabreiro, Host-microbe-drug-nutrient screen identifies bacterial effectors of metformin therapy. Cell 178(6), 1299–1312.e29 (2019). https://doi.org/10.1016/j.cell.2019.08.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

The study was supported by the National Natural Science Foundation of China, under contract No. 31471202 (L.Z.), 81570712 (Z.W.); the Shandong Provincial Key Research and Development Program under contract No. 2016YYSP009 (L.Z.), 2016GSF201009 (Z.W.); Natural Science Outstanding Youth Foundation of Shandong Province, under contract No. JQ201519 (Q.Z.); Major Science and Technology Innovation Project of Shandong Province, under contract No. 2018CXGC1218 and No. 2018CXGC1219; Weihai Technique Extension Project under contract No. 2016GNS023 (L.Z.), L.Z. was also supported by the TaiShan Scholars Program of Shandong Province (No. tshw20120206) and TaiShan Industrial Experts Program (No. tscy20190612).

Author information

Authors and Affiliations

Authors

Contributions

L.Z. and Q.Z. designed the study. B.C., Z.W., J.W., X.S., and J.Y. performed measurements and data analysis. Z.W., Q.Z., and X.S. obtained samples and clinical details. B.C. and J.W. wrote the manuscript. All authors have read and critically revised the manuscript.

Corresponding authors

Correspondence to Qunye Zhang or Lei Zhang.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in the above studies involving human participants were in accordance with the ethical standards of the institution and/or national research committee and with the 1964 Declaration of Helsinki along with its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, B., Wang, Z., Wang, J. et al. The oral microbiome profile and biomarker in Chinese type 2 diabetes mellitus patients. Endocrine 68, 564–572 (2020). https://doi.org/10.1007/s12020-020-02269-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-020-02269-6

Keywords

Navigation