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

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

doi:10.3389/froh.2021.722495

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.

Highlights

The dysbiotic microbiota in periodontitis-affected subgingival sites is characterized by an increased abundance of pathogens and pathobionts whereas the abundance of genera considered as beneficial to the host is decreased [1, 2]
We aimed to evaluate the microbial communities of nontreated patients with periodontitis by accessing the microbiomes of supra and subgingival sites, and feces and to correlate the oral microbiome with levels of inflammatory mediators in saliva
The studied population comprised periodontitis subjects who were compared to age-matched periodontal healthy subjects, FIGURE 3 | Phylum distribution in samples of the oral sites and feces (A); (B–D): Fold changes relative abundance of species in periodontitis samples compared to control—in: (B) supragingival biofilm (C) subgingival non- affected sites of periodontitis patients and health patients; (D) subgingival affected sites of periodontitis patients compared to subgingival sites of H; (E) fold changes of Relative abundance of families in feces and (F) genera in feces

Summary

Introduction

The dysbiotic microbiota in periodontitis-affected subgingival sites is characterized by an increased abundance of pathogens and pathobionts whereas the abundance of genera considered as beneficial to the host is decreased [1, 2]. There is evidence of altered gut microbiome in Grade B periodontitis (previously known as chronic periodontitis) [12], and Grade C periodontitis of the molar incisor pattern (previously known as localized aggressive periodontitis) [13]. These observations led to the hypothesis that alterations in the gut microbiome play a key role in periodontitis and its association with inflammatory diseases [14,15,16,17]

Objectives

Methods

Results

Conclusion