Skip to main content

Advertisement

SpringerLink
Log in

Characteristics of the oral microbiota in patients with primary Sjögren’s syndrome

  • ORIGINAL ARTICLE
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

Objective

Primary Sjögren’s syndrome (pSS) is an autoimmune disease with unknown etiology that is considered to be related to environmental and genetic factors. The aim of this study was to clarify the oral microflora characteristics of pSS patients and to reveal the connection between oral bacterial composition and dental caries using a high-throughput sequencing technique.

Methods

Thirty-five pSS patients and 20 healthy controls were enrolled in this study. We collected saliva and plaque samples from pSS patients and saliva samples from healthy controls. We used 16S ribosomal DNA (16S rDNA) high-throughput sequencing targeting the V3–V4 hypervariable region to determine the composition and structure of the microbiota in the three sample sets. Finally, bioinformatics analyses, including the diversity of the microbiota, species differences, and functional prediction were performed.

Results

In the alpha diversity and beta diversity analysis, the Chao1 (P < 0.01), observed species (P < 0.01), and PD whole tree indices (P < 0.01) were significantly lower in the saliva and plaque samples of pSS patients than in the saliva samples of healthy controls, but the Shannon (P < 0.01) and Simpson indices (P < 0.01) were significantly higher in the healthy controls, and their total diversity significantly differed. In the main flora composition at the genus level (top 10), we identified Prevotella and Veillonella as more enriched in the saliva of pSS patients and Fusobacterium, Actinomyces, and Leptotrichia as more enriched in the plaque of pSS patients. Predictive functional analysis showed that the oral microbiota of pSS patients was related to translation, metabolism of cofactors and vitamins, and nucleotide metabolism.

Conclusions

The oral microbial ecology of patients with pSS is dysregulated, resulting in a decrease in overall diversity. Prevotella and Veillonella may be related to pSS, while Fusobacterium, Actinomyces, and Leptotrichia may be related to dental caries in pSS patients.

Key Points

• This study revealed differences in the oral microbial composition of patients with pSS compared to healthy controls.

• We included a plaque group of pSS patients to identify the microbiota related to pSS and dental caries.

• Prevotella and Veillonella may contribute to pSS, and Fusobacterium, Actinomyces, and Leptotrichia are associated with dental caries in pSS patients.

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
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data Availability

Data available on request from the authors.

References

  1. Ramos-Casals M, Brito-Zerón P, Sisó-Almirall A, Bosch X (2012) Primary Sjogren syndrome. Bmj 344:e3821

    Article  PubMed  Google Scholar 

  2. Kuo CF, Grainge MJ, Valdes AM, See LC, Luo SF, Yu KH, Zhang W, Doherty M (2015) Familial risk of Sjögren’s syndrome and co-aggregation of autoimmune diseases in affected families: a nationwide population study. Arthritis Rheumatol 67(7):1904–1912

    Article  PubMed  PubMed Central  Google Scholar 

  3. Marcotte H, Lavoie MC (1998) Oral microbial ecology and the role of salivary immunoglobulin A. Microbiol Mol Biol Rev 62(1):71–109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Brito-Zerón P, Baldini C, Bootsma H, Bowman SJ, Jonsson R, Mariette X, Sivils K, Theander E, Tzioufas A, Ramos-Casals M (2016) Sjögren syndrome. Nat Rev Dis Primers 2:16047

    Article  PubMed  Google Scholar 

  5. Zhou Z, Ling G, Ding N, Xun Z, Zhu C, Hua H, Chen X (2018) Molecular analysis of oral microflora in patients with primary Sjögren’s syndrome by using high-throughput sequencing. PeerJ 6:e5649

    Article  PubMed  PubMed Central  Google Scholar 

  6. Zhang Y, Wang X, Li H, Ni C, Du Z, Yan F (2018) Human oral microbiota and its modulation for oral health. Biomed Pharmacother 99:883–893

    Article  PubMed  Google Scholar 

  7. Doaré E, Héry-Arnaud G, Devauchelle-Pensec V, Alegria GC (2021) Healthy patients are not the best controls for microbiome-based clinical studies: example of Sjögren’s syndrome in a systematic review. Front Immunol 12:699011

    Article  PubMed  PubMed Central  Google Scholar 

  8. Gross EL, Leys EJ, Gasparovich SR, Firestone ND, Schwartzbaum JA, Janies DA, Asnani K, Griffen AL (2010) Bacterial 16S sequence analysis of severe caries in young permanent teeth. J Clin Microbiol 48(11):4121–4128

    Article  PubMed  PubMed Central  Google Scholar 

  9. Wilson K (2001) Preparation of genomic DNA from bacteria. Curr Protoc Mol Biol 56:2.4.1–2.4.5. https://doi.org/10.1002/047114272

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

    Article  PubMed  PubMed Central  Google Scholar 

  11. Bokulich NA, Subramanian S, Faith JJ, Gevers D, Gordon JI, Knight R, Mills DA, Caporaso JG (2013) Quality-filtering vastly improves diversity estimates from Illumina amplicon sequencing. Nat Methods 10(1):57–59

    Article  CAS  PubMed  Google Scholar 

  12. Caporaso JG, Kuczynski J, Stombaugh J, Bittinger K, Bushman FD, Costello EK, Fierer N, Peña AG, Goodrich JK, Gordon JI et al (2010) QIIME allows analysis of high-throughput community sequencing data. Nat Methods 7(5):335–336

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Edgar RC, Haas BJ, Clemente JC, Quince C, Knight R (2011) UCHIME improves sensitivity and speed of chimera detection. Bioinformatics 27(16):2194–2200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Haas BJ, Gevers D, Earl AM, Feldgarden M, Ward DV, Giannoukos G, Ciulla D, Tabbaa D, Highlander SK, Sodergren E et al (2011) Chimeric 16S rRNA sequence formation and detection in Sanger and 454-pyrosequenced PCR amplicons. Genome Res 21(3):494–504

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Qian Y, Yang X, Xu S, Wu C, Song Y, Qin N, Chen SD, Xiao Q (2018) Alteration of the fecal microbiota in Chinese patients with Parkinson’s disease. Brain Behav Immun 70:194–202

    Article  PubMed  Google Scholar 

  16. Wahren-Herlenius M, Dörner T (2013) Immunopathogenic mechanisms of systemic autoimmune disease. Lancet 382(9894):819–831

    Article  CAS  PubMed  Google Scholar 

  17. Qin B, Wang J, Yang Z, Yang M, Ma N, Huang F, Zhong R (2015) Epidemiology of primary Sjögren’s syndrome: a systematic review and meta-analysis. Ann Rheum Dis 74(11):1983–1989

    Article  CAS  PubMed  Google Scholar 

  18. van der Meulen TA, Harmsen H, Bootsma H, Spijkervet F, Kroese F, Vissink A (2016) The microbiome-systemic diseases connection. Oral Dis 22(8):719–734

    Article  PubMed  Google Scholar 

  19. Rusthen S, Kristoffersen AK, Young A, Galtung HK, Petrovski B, Palm Ø, Enersen M, Jensen JL (2019) Dysbiotic salivary microbiota in dry mouth and primary Sjögren’s syndrome patients. PLoS ONE 14(6):e0218319

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. van der Meulen TA, Harmsen HJM, Bootsma H, Liefers SC, Vich Vila A, Zhernakova A, Fu J, Wijmenga C, Spijkervet FKL, Kroese FGM et al (2018) Dysbiosis of the buccal mucosa microbiome in primary Sjögren’s syndrome patients. Rheumatology (Oxford) 57(12):2225–2234

    Article  PubMed  Google Scholar 

  21. Zhou S, Cai Y, Wang M, Yang WD, Duan N (2018) Oral microbial flora of patients with Sicca syndrome. Mol Med Rep 18(6):4895–4903

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Siddiqui H, Chen T, Aliko A, Mydel PM, Jonsson R, Olsen I (2016) Microbiological and bioinformatics analysis of primary Sjogren’s syndrome patients with normal salivation. J Oral Microbiol 8:31119

    Article  PubMed  Google Scholar 

  23. Gao X, Jiang S, Koh D, Hsu CY (2016) Salivary biomarkers for dental caries. Periodontol 2000 70(1):128–141

    Article  PubMed  Google Scholar 

  24. Könönen E, Fteita D, Gursoy UK, Gursoy M (2022) Prevotella species as oral residents and infectious agents with potential impact on systemic conditions. J Oral Microbiol 14(1):2079814

    Article  PubMed  PubMed Central  Google Scholar 

  25. Alam J, Lee A, Lee J, Kwon DI, Park HK, Park JH, Jeon S, Baek K, Lee J, Park SH et al (2020) Dysbiotic oral microbiota and infected salivary glands in Sjögren’s syndrome. PLoS ONE 15(3):e0230667

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Zhou P, Manoil D, Belibasakis GN, Kotsakis GA (2021) Veillonellae: beyond bridging species in oral biofilm ecology. Front Oral Health 2:774115

    Article  PubMed  PubMed Central  Google Scholar 

  27. Fujiwara N, Kitamura N, Yoshida K, Yamamoto T, Ozaki K, Kudo Y (2020) Involvement of Fusobacterium species in oral cancer progression: a literature review including other types of cancer. Int J Mol Sci 21(17):6207

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Konig MF (2020) The microbiome in autoimmune rheumatic disease. Best Pract Res Clin Rheumatol 34(1):101473

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank the patients and healthy volunteers who made this study possible and provided their plaque or saliva samples.

Funding

This work was supported by grants from the Shantou Medical Health Science and Technology Plan (No. 2019–106-21) and the Medical Science Research Foundation of Guangdong Province (No. A2019244).

Author information

Author notes

  1. Yiwen Xie and Yu Fan contributed equally to this work.

Authors and Affiliations

  1. Department of Stomatology, Shantou Central Hospital, Shantou, 515041, China

    Yiwen Xie

  2. Department of Pathology, Shantou University Medical College, Shantou, 515041, China

    Yu Fan, Miaotong Su & Guohong Zhang

  3. Department of Rheumatology and Immunology, Shantou Central Hospital, Shantou, 515041, China

    Yukai Wang

Authors
  1. Yiwen Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yu Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Miaotong Su
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yukai Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Guohong Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Clinical analyses and manuscript writing: Yiwen Xie and Yu Fan.

Sample and data collection: Miaotong Su and Yukai Wang.

Statistical analyses: All authors.

Study design: Yiwen Xie and Guohong Zhang.

Corresponding authors

Correspondence to Yiwen Xie or Guohong Zhang.

Ethics declarations

Ethics approval

The sample collection was approved by the Regional Ethics Board of Shantou Central Hospital (approval number, 2019-scientific research (042)), and written informed consent was obtained from all participants.

Disclosures

None.

Additional information

Publisher's Note

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

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xie, Y., Fan, Y., Su, M. et al. Characteristics of the oral microbiota in patients with primary Sjögren’s syndrome. Clin Rheumatol (2024). https://doi.org/10.1007/s10067-024-06958-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10067-024-06958-9

Keywords

Search

Navigation