Oral Dysbiosis in Severe Forms of Periodontitis Is Associated With Gut Dysbiosis and Correlated With Salivary Inflammatory Mediators: A Preliminary Study

Dione Kawamoto; Rodrigo Borges; Rodolfo Alvarenga Ribeiro; Robson Franciso de Souza; Pâmela Pontes Penas Amado; Luciana Saraiva; Ana Carolina Ratto Tempestini Horliana; Marcelo Faveri; Marcia Pinto Alves Mayer

doi:10.3389/froh.2021.722495

Oral Dysbiosis in Severe Forms of Periodontitis Is Associated With Gut Dysbiosis and Correlated With Salivary Inflammatory Mediators: A Preliminary Study

Front Oral Health. 2021 Oct 11:2:722495. doi: 10.3389/froh.2021.722495. eCollection 2021.

Authors

Dione Kawamoto¹, Rodrigo Borges², Rodolfo Alvarenga Ribeiro¹, Robson Franciso de Souza¹, Pâmela Pontes Penas Amado¹, Luciana Saraiva³, Ana Carolina Ratto Tempestini Horliana⁴, Marcelo Faveri⁵, Marcia Pinto Alves Mayer^{1

3}

Affiliations

¹ Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
² Laboratório de Biologia Computacional e Bioinformática, Centro Internacional de Pesquisa (CIPE) - A.C. Camargo Cancer Center, São Paulo, Brazil.
³ Division of Periodontology, Department of Stomatology, School of Dentistry, University of São Paulo, São Paulo, Brazil.
⁴ Biophotonics Applied to Health Sciences, University Nove de Julho, São Paulo, Brazil.
⁵ Dental Research Division, Department of Periodontology, Guarulhos University, Guarulhos, Brazil.

Abstract

Inflammation is a driven force in modulating microbial communities, but little is known about the interplay between colonizing microorganisms and the immune response in periodontitis. Since local and systemic inflammation may play a whole role in disease, we aimed to evaluate the oral and fecal microbiome of patients with periodontitis and to correlate the oral microbiome data with levels of inflammatory mediator in saliva. Methods: Nine patients with periodontitis (P) in Stage 3/Grade B and nine age-matched non-affected controls (H) were evaluated. Microbial communities of oral biofilms (the supra and subgingival from affected and non-affected sites) and feces were determined by sequencing analysis of the 16SrRNA V3-V4 region. Salivary levels of 40 chemokines and cytokines were correlated with oral microbiome data. Results: Supragingival microbial communities of P differed from H (Pielou's evenness index, and Beta diversity, and weighted UniFrac), since relative abundance (RA) of Defluviitaleaceae, Desulfobulbaceae, Mycoplasmataceae, Peptostreococcales-Tissierellales, and Campylobacteraceae was higher in P, whereas Muribaculaceae and Streptococcaceae were more abundant in H. Subgingival non-affected sites of P did not differ from H, except for a lower abundance of Gemellaceae. The microbiome of affected periodontitis sites (PD ≥ 4 mm) clustered apart from the subgingival sites of H. Oral pathobionts was more abundant in sub and supragingival biofilms of P than H. Fecal samples of P were enriched with Acidaminococcus, Clostridium, Lactobacillus, Bifidobacterium, Megasphaera, and Romboutsia when compared to H. The salivary levels of interleukin 6 (IL-6) and inflammatory chemokines were positively correlated with the RA of several recognized and putative pathobionts, whereas the RA of beneficial species, such as Rothia aeria and Haemophilus parainfluenzae was negatively correlated with the levels of Chemokine C-C motif Ligand 2 (CCL2), which is considered protective. Dysbiosis in patients with periodontitis was not restricted to periodontal pockets but was also seen in the supragingival and subgingival non-affected sites and feces. Subgingival dysbiosis revealed microbial signatures characteristic of different immune profiles, suggesting a role for candidate pathogens and beneficial organisms in the inflammatory process of periodontitis.

Keywords: 16SrRNA sequencing; dysbiosis; fecal microbiome; oral microbiome; periodontitis.