Skip to main content

Advertisement

SpringerLink
Log in

Chicken or the Egg: Microbial Alterations in Biopsy Samples of Patients with Oral Potentially Malignant Disorders

  • Original Article
  • Published:
Pathology & Oncology Research

Abstract

Oral carcinogenesis often leads to the alteration of the microbiota at the site of the tumor, but data are scarce regarding the microbial communities of oral potentially malignant disorders (OPMDs). Punch biopsies were taken from healthy and non-healthy mucosa of OPMD patients to analyze the microbiome using metagenome sequencing. In healthy oral mucosa biopsies the bacterial phyla Firmicutes, Fusobacteria, Proteobacteria, Actinobacteria and Bacteroidetes were detected by Ion Torrent sequencing. The same phyla as well as the phyla Fibrobacteres and Spirochaetes were present in the OPMD biopsies. On the species level, there were 10 bacterial species unique to the healthy tissue and 35 species unique to the OPMD lesions whereas eight species were detected in both samples. We observed that the relative abundance of Streptococcus mitis decreased in the OPMD lesions compared to the uninvolved tissue. In contrast, the relative abundance of Fusobacterium nucleatum, implicated in carcinogenesis, was elevated in OPMD. We detected markedly increased bacterial diversity in the OPMD lesions compared to the healthy oral mucosa. The ratio of S. mitis and F. nucleatum are characteristically altered in the OPMD lesions compared to the healthy mucosa.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1: Representative pictures from OPMD tissue samples
Fig. 2: Distribution of taxonomic domains
Fig. 3: Bacterial diversity
Fig. 4: Comparison of the detected bacterial species
Fig. 5: Ratio of Streptococci in the mucosal lesion
Fig. 6: Fusobacterium nucleatum in the mucosal lesion
Fig. 7: Fusobacterium nucleatum-specific PCR of the healthy tissue and the OPMD

Similar content being viewed by others

References

  1. Morse DE, Psoter WJ, Cleveland D et al (2007) Smoking and drinking in relation to oral cancer and oral epithelial dysplasia. Cancer Causes Control 18(9):919–929

    Article  PubMed  PubMed Central  Google Scholar 

  2. Jepsen SA, Closmann JJ (2008) The insidious nature and presentation of oral squamous cell carcinoma in the low-risk population. Gen Dent 56(1):78–82

    PubMed  Google Scholar 

  3. Llewellyn CD, Linklater K, Bell J et al (2003) Squamous cell carcinoma of the oral cavity in patients aged 45 years and under: a descriptive analysis of 116 cases diagnosed in the South East of England from 1990 to 1997. Oral Oncol 39(2):106–114

    Article  CAS  PubMed  Google Scholar 

  4. Nagy KN, Sonkodi I, Szöke I et al (1998) The microflora associated with human oral carcinomas. Oral Oncol 34(4):304–308

    Article  CAS  PubMed  Google Scholar 

  5. Sarode SC, Sarode GS, Tupkari JV (2012) Oral potentially malignant disorders: precising the definition. Oral Oncol 48(9):759–760

    Article  PubMed  Google Scholar 

  6. van der Waal I (2009) Potentially malignant disorders of the oral and oropharyngeal mucosa; terminology, classification and present concepts of management. Oral Oncol 45(4–5):317–323

    Article  PubMed  Google Scholar 

  7. Sonkodi I (2009) Oral and Maxilofacial medicine. Semmelweis Publisher, Budapest

    Google Scholar 

  8. Silverman S Jr, Gorsky M (1997) Proliferative verrucous leukoplakia. A follow-up study of 54 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 84(2):154–157

    Article  PubMed  Google Scholar 

  9. Fehér E, Gáll T, Murvai M et al (2009) Investigation of the occurrence of torque tenovirus in malignant and potentially malignant disorders associated with human papillomavirus. J Med Virol 81(11):1975–1981

    Article  CAS  PubMed  Google Scholar 

  10. Fehér E, Kardos G, Gáll T et al (2011) Comparison of diversity of torque teno virus 1 in different mucosal tissues and disorders. Acta Microbiol Immunol Hung 58(4):319–337

    Article  PubMed  Google Scholar 

  11. Kis A, Fehér E, Gáll T et al (2009) Epstein-Barr virus prevalence in oral squamous cell cancer and in potentially malignant oral disorders in an eastern Hungarian population. Eur J Oral Sci 117(5):536–540

    Article  CAS  PubMed  Google Scholar 

  12. Wu L, Feng J, Shi L et al (2013) Candidal infection in oral leukoplakia: a clinicopathologic study of 396 patients from eastern China. Ann Diagn Pathol 17(1):37–40

    Article  CAS  PubMed  Google Scholar 

  13. Hebbar PB, Pai A, D S. (2013) Mycological and histological associations of Candida in oral mucosal lesions. J Oral Sci 55(2):157–160

    Article  PubMed  Google Scholar 

  14. Dilhari A, Weerasekera MM, Siriwardhana A et al (2016) Candida infection in oral leukoplakia: an unperceived public health problem. Acta Odontol Scand 74(7):565–569

    Article  CAS  PubMed  Google Scholar 

  15. Gainza-Cirauqui ML, Nieminen MT, Novak Frazer L et al (2013) Production of carcinogenic acetaldehyde by Candida albicans from patients with potentially malignant oral mucosal disorders. J Oral Pathol Med. 42(3):243–249

    Article  CAS  PubMed  Google Scholar 

  16. Bakri MM, Cannon RD, Holmes AR et al (2014) Detection of Candida albicans ADH1 and ADH2 mRNAs in human archival oral biopsy samples. J Oral Pathol Med 43(9):704–710

    Article  CAS  PubMed  Google Scholar 

  17. Kazanowska-Dygdała M, Duś I, Radwan-Oczko M (2016) The presence of helicobacter pylori in oral cavities of patientsn with leukoplakia and oral lichenplanus. J Appl Oral Sci 24(1):18–23

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Mizuki H, Kawamura T, Nagasawa D (2015) In situ immunohistochemical detection of intracellular mycoplasma salivarium in the epithelial cells of oral leukoplakia. J Oral Pathol Med. 44(2):134–144

    Article  CAS  PubMed  Google Scholar 

  19. Meisel P, Holtfreter B, Biffar R et al (2012) Association of periodontitis with the risk of oral leukoplakia. Oral Oncol 48(9):859–863

    Article  PubMed  Google Scholar 

  20. Hu X, Zhang Q, Hua H et al (2016) Changes in the salivary microbiota of oral leukoplakia and oral cancer. Oral Oncol 56:e6–e8

    Article  PubMed  Google Scholar 

  21. Hernandez BY, Zhu X, Goodman MT et al (2017) Betel nut chewing, oral premalignant lesions, and the oral microbiome. PLoS One 12(2):e0172196

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Srinivas K, Aravinda K, Ratnakar P et al (2011) Oral lichen planus – Review on etiopathogenesis. Natl J Maxillofac Surg 2(1):15–16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Payeras MR, Cherubini K, Figueiredo MA et al (2013) Oral lichen planus: focus on etiopathogenesis. Arch Oral Biol 58(9):1057–1069

    Article  CAS  PubMed  Google Scholar 

  24. Georgakopoulou EA, Achtari MD, Achtaris M et al (2012) Oral lichen planus as a preneoplastic inflammatory model. J Biomed Biotechnol 2012:759626

    Article  PubMed  PubMed Central  Google Scholar 

  25. Roopashree MR, Gondhalekar RV, Shashikanth MC et al (2010) Pathogenesis of oral lichen planus--a review. J Oral Pathol Med. 39(10):729–734

    Article  CAS  PubMed  Google Scholar 

  26. Gorouhi F, Davari P, Fazel N (2014) Cutaneous and mucosal lichen planus: a comprehensive review of clinical subtypes, risk factors, diagnosis, and prognosis. ScientificWorld Journal 2014:742826

    Article  CAS  PubMed  Google Scholar 

  27. Bäckman K, Jontell M (2007) Microbial-associated oral lichenoid reactions. Oral Dis 13(4):402–406

    Article  PubMed  Google Scholar 

  28. Taghavi Zenouz A, Mehdipour M, Jafari Heydarlou M et al (2010) Relationship between Lichen Planus and Helicobacter pylori Infection. J Dent Res Dent Clin Dent Prospects 4(1):17–20

    PubMed  PubMed Central  Google Scholar 

  29. Attia EA, Abdel Fattah NS, Abdella HM (2010) Upper gastrointestinal findings and detection of helicobacter pylori in patients with oral lichen planus. Clin Exp Dermatol 35(4):355–360

    Article  CAS  PubMed  Google Scholar 

  30. Pourshahidi S, Fakhri F, Ebrahimi H et al (2012) Lack of association between helicobacter pylori infection and oral lichen planus. Asian Pac J Cancer Prev 13(5):1745–1747

    Article  PubMed  Google Scholar 

  31. Izol B, Karabulut AA, Biyikoglu I et al (2010) Investigation of upper gastrointestinal tract involvement and H. Pylori presence in lichen planus: a case-controlled study with endoscopic and histopathological findings. Int J Dermatol 49(10):1121–1126

    Article  PubMed  Google Scholar 

  32. Hulimavu SR, Mohanty L, Tondikulam NV et al (2014) No evidence for Helicobacter pylori in oral lichen planus. J Oral Pathol Med. 43(8):576–578

    Article  PubMed  Google Scholar 

  33. Boorghani M, Gholizadeh N, Taghavi Zenouz A et al (2010) Oral lichen planus: clinical features, etiology, treatment and management; a review of literature. J Dent Res Dent Clin Dent Prospects. 4(1):3–9

    PubMed  PubMed Central  Google Scholar 

  34. Ertugrul AS, Arslan U, Dursun R et al (2013) Periodontopathogen profile of healthy and oral lichen planus patients with gingivitis or periodontitis. Int J Oral Sci 5(2):92–97

    Article  PubMed  Google Scholar 

  35. El-Naggar AK, Chan JKC, Takata T, Grandis JR, Slootweg PJ (2017) Tumours of the oral cavity and mobile tongue In: The fourth edition of the head and neck World Health Organization blue book: editors' perspectives. Hum Pathol 66:10–12

    Article  PubMed  Google Scholar 

  36. Sharma PK, Capalash N, Kaur J (2007) An improved method for single step purification of metagenomic DNA. Mol Biotechnol 36(1):61–63

    Article  CAS  PubMed  Google Scholar 

  37. Periasamy S, Chalmers NI, Du-Thumm L et al (2009) Fusobacterium nucleatum ATCC 10953 requires Actinomyces naeslundii ATCC 43146 for growth on saliva in a three-species community that includes Streptococcus oralis 34. Appl Environ Microbiol 75(10):3250–3257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Rubinstein MR, Wang X, Liu W et al (2013) Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/β-catenin signaling via its FadA adhesion. Cell Host Microbe 14(2):195–206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Schmidt BL, Kuczynski J, Bhattacharya A et al (2014) Changes in abundance of oral microbiota associated with oral cancer. PLoS One 9(6):e98741

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Al-Hebshi NN, Nasher AT, Maryoud MY et al (2017) Inflammatory bacteriome featuring fusobacterium nucleatum and Pseudomonas aeruginosa identified in association with oral squamous cell carcinoma. Sci Rep 7(1):1834

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Arduino PG, Romano F, Sasia D et al (2017) Subgingival microbiota in white patients with Desquamative gingivitis: a cross-sectional study. J Periodontol 88(7):643–650

    Article  PubMed  Google Scholar 

  42. Kreth J, Merritt J, Qi F (2009) Bacterial and host interactions of oral streptococci. DNA Cell Biol 28(8):397–403

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Van Hoogmoed CG, Geertsema-Doornbusch GI, Teughels W et al (2008) Reduction of periodontal pathogens adhesion by antagonistic strains. Oral Microbial Immunol 23(1):43–48

    Article  Google Scholar 

  44. Standar K, Kreikemeyer B, Redanz S et al (2010) Setup of an in vitro test system for basic studies on biofilm behavior of mixed-species cultures with dental and periodontal pathogens. PLoS One 5(10):e13135

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Otsuki K, Imai N (2017) Effects of lactoferrin in 6 patients with refractory bacterial vaginosis. Biochem Cell Biol 95(1):31–33

    Article  CAS  PubMed  Google Scholar 

  46. Klarić M, Mandić V, Lovrić S, e al. (2017) Antimicrobial efficacy of probiotic-containing toothpastes: an in vitro evaluation. Med Glas (Zenica) 14(1):16–24

    Google Scholar 

Download references

Acknowledgements

This work was in part supported by the National Research, Development and Innovation Fund of Hungary, financed under the NKFI-6-K funding scheme (11493 project), GINOP-2.3.2-15-2016-00015, János Bolyai Research Scholarship of the Hungarian Academy of Sciences and GINOP 2.3.2-15-2016-00011.

Author information

Authors and Affiliations

  1. Faculty of Dentistry, Department of Oral Surgery, University of Szeged, Tisza Lajos krt. 64, Szeged, H-6720, Hungary

    Gabor Decsi, Istvan Sonkodi & Katalin Nagy

  2. Albert Szent-Gyorgyi Clinical Centre, Institute of Clinical Microbiology, University of Szeged, Semmelweis u. 6, Szeged, H-6725, Hungary

    Jozsef Soki & Edit Urban

  3. Biological Research Centre, Hungarian Academy of Sciences, Temesvari krt. 62, Szeged, H-6726, Hungary

    Bernadett Pap, Gabriella Dobra, Maria Harmati & Krisztina Buzas

  4. Albert Szent-Gyorgyi Clinical Centre, Department of Traumatology, University of Szeged, Semmelweis u. 6, Szeged, H-6725, Hungary

    Sandor Kormondi

  5. Department of Biochemistry and Molecular Biology, University of Szeged, Kozep fasor 52, Szeged, H-6726, Hungary

    Tibor Pankotai

  6. dicomLAB Ltd., Pulz u. 46/b, Szeged, H-6724, Hungary

    Gabor Braunitzer

  7. Faculty of Dentistry, Department of Oral Biology and Experimental Dental Research, University of Szeged, Tisza Lajos krt. 64, Szeged, H-6720, Hungary

    Janos Minarovits & Krisztina Buzas

  8. Department of Dermatology and Allergology, University of Szeged, Szeged, H-6720, Hungary

    Istvan Balazs Nemeth

Authors
  1. Gabor Decsi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jozsef Soki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bernadett Pap
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gabriella Dobra
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Maria Harmati
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sandor Kormondi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tibor Pankotai
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Gabor Braunitzer
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Janos Minarovits
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Istvan Sonkodi
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Edit Urban
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Istvan Balazs Nemeth
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Katalin Nagy
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Krisztina Buzas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Krisztina Buzas.

Ethics declarations

Conflict of Interest

No potential conflict of interest was reported by the authors.

Ethical Approval

The study protocol conformed to the Declaration of Helsinki in all respects and was approved by the Institutional Ethics Committee of the University of Szeged (No. 3161).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Decsi, G., Soki, J., Pap, B. et al. Chicken or the Egg: Microbial Alterations in Biopsy Samples of Patients with Oral Potentially Malignant Disorders. Pathol. Oncol. Res. 25, 1023–1033 (2019). https://doi.org/10.1007/s12253-018-0457-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12253-018-0457-x

Keywords

Search

Navigation