Shotgun metagenomic analysis of the oral microbiome in gingivitis: a nested case-control study

ABSTRACT

Background

Gingivitis, i.e. inflammation of the gums, is often induced by dental plaque. However, its exact link to the oral microbiota remains unclear.

Methods

In a case-control study involving 120 participants, comprising 60 cases and 60 controls (mean age (SD) 36.6 (7.6) years; 50% males), nested within a prospective multicentre cohort study, we examined the oral microbiome composition of gingivitis patients and their controls using shotgun metagenomic sequencing of saliva samples. Participants underwent clinical and radiographic oral health examinations, including bleeding on probing (BOP), at six tooth sites. BOP ≥33% was considered ‘generalized gingivitis/initial periodontitis’(GG/IP), and BOP <33% as ‘healthy and localized gingivitis’(H/LG). Functional potential was inferred using HUMANn3.

Results

GG/IP exhibited an increase in the abundance of Actinomyces, Porphyromonas, Aggregatibacter, Corynebacterium, Olsenella, and Treponema, whereas H/LG exhibited an increased abundance of Candidatus Nanosynbacter. Nineteen bacterial species and four microbial functional profiles, including L-methionine, glycogen, and inosine-5’-phosphate biosynthesis, were associated with GG/IP. Constructing models with multiple markers resulted in a strong predictive value for GG/IP, with an area under the curve (ROC) of 0.907 (95% CI: 0.848-0.966).

Conclusion

We observed distinct differences in the oral microbiome between the GG/IP and H/LG groups, indicating similar yet unique microbial profiles and emphasizing their potential role in progression of periodontal diseases.

KEYWORDS:

• Metagenomics
• oral microbiome
• periodontal disease
• chronic periodontitis
• saliva
• biomarker
• dysbiosis
• diversity
• prediction

Acknowledgments

The authors are grateful to the study subjects who participated in the SECRETO Oral study. The Biomedicum Functional Genomics Unit (FuGU) is acknowledged for assistance with metagenomic sequencing.

Disclosure statement

No potential conflict of interest was reported by the authors.

Data availability statement

The data supporting the findings of this study are available upon request from the corresponding author.

Ethical approval

The study was approved by the Ethics Committee of the Hospital District of Helsinki and Uusimaa. All participating centres obtained approvals from the responsible local Ethics Committees. The study was performed in accordance with Good Clinical Practice and the Declaration of Helsinki. All participants in this study provided written informed consent.

Author contributions statement

Conceived and designed the study: MM, JL, JP, JS, PJP, SP.

Performed the clinical work: JL, NMM, EK, JS, JP, SP.

Analysed the data: MM, JL, PJP, SP.

Funding acquisition: JP, PJP, SP.

Writing – original draft preparation: MM.

Writing – review and editing: MM, JL, MP, NMM, EK, TN, LL, JS, JP, PJP, SP.

All authors read and approved the final manuscript.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/20002297.2024.2330867

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This work was supported by the Academy of Finland grants [316777 and 355532 for SP; 340750 for PJP], the Finnish Dental Society Apollonia [for PJP], the Sigrid Jusélius Foundation [for PJP], and the Novo Nordisk Foundation [for PJP]. The SECRETO study was funded by the Academy of Finland, the Helsinki and Uusimaa Hospital District, and the Sigrid Jusélius Foundation. The funders had no role in the design or execution of the study; the collection, management, analysis, or interpretation of data; the preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication.