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

Muhammed Manzoor; Jaakko Leskelä; Milla Pietiäinen; Nicolas Martinez-Majander; Eija Könönen; Teemu Niiranen; Leo Lahti; Juha Sinisalo; Jukka Putaala; Pirkko J Pussinen; Susanna Paju

doi:10.1080/20002297.2024.2330867

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

J Oral Microbiol. 2024 Mar 22;16(1):2330867. doi: 10.1080/20002297.2024.2330867. eCollection 2024.

Authors

Muhammed Manzoor¹, Jaakko Leskelä¹, Milla Pietiäinen^{1

2}, Nicolas Martinez-Majander³, Eija Könönen⁴, Teemu Niiranen^{5

6}, Leo Lahti⁷, Juha Sinisalo⁸, Jukka Putaala³, Pirkko J Pussinen^{1

9}, Susanna Paju¹

Affiliations

¹ Department of Oral and Maxillofacial Diseases, University of Helsinki, Helsinki, Finland.
² Industrial Biotechnology and Food Protein Production, VTT Technical Research Centre of Finland, Espoo, Finland.
³ Department of Neurology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
⁴ Institute of Dentistry, University of Turku, Turku, Finland.
⁵ Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland.
⁶ Department of Internal Medicine, Turku University Hospital and University of Turku, Turku, Finland.
⁷ Department of Computing, University of Turku, Turku, Finland.
⁸ Heart and Lung Center, Helsinki University Central Hospital, and Helsinki University, Helsinki, Finland.
⁹ School of Medicine, Institute of Dentistry, University of Eastern Finland, Kuopio, Finland.

Abstract

Background: Gingivitis, i.e. inflammation of the gums, is often induced by dentalplaque. 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 theoral microbiome composition of gingivitis patients and their controlsusing 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 fourmicrobial functional profiles, including L-methionine, glycogen, andinosine-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; biomarker; chronic periodontitis; diversity; dysbiosis; oral microbiome; periodontal disease; prediction; saliva.

Grants and 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.