Abstract
Empiric antibiotics are often used in combination with mechanical debridement to treat patients suffering from periodontitis and to eliminate disease-associated pathogens. Until now, only a few next generation sequencing 16S rDNA amplicon based publications with rather small sample sizes studied the effect of those interventions on the subgingival microbiome. Therefore, we studied subgingival samples of 89 patients with chronic periodontitis (solely non-smokers) before and two months after therapy. Forty-seven patients received mechanical periodontal therapy only, whereas 42 patients additionally received oral administered amoxicillin plus metronidazole (500 and 400 mg, respectively; 3x/day for 7 days). Samples were sequenced with Illumina MiSeq 300 base pairs paired end technology (V3 and V4 hypervariable regions of the 16S rDNA). Inter-group differences before and after therapy of clinical variables (percentage of sites with pocket depth ≥ 5mm, percentage of sites with bleeding on probing) and microbiome variables (diversity, richness, evenness, and dissimilarity) were calculated, a principal coordinate analysis (PCoA) was conducted, and differential abundance of agglomerated ribosomal sequence variants (aRSVs) classified on genus level was calculated using a negative binomial regression model. We found statistically noticeable decreased richness, and increased dissimilarity in the antibiotic, but not in the placebo group after therapy. The PCoA revealed a clear compositional separation of microbiomes after therapy in the antibiotic group, which could not be seen in the group receiving mechanical therapy only. This difference was even more pronounced on aRSV level. Here, adjunctive antibiotics were able to induce a microbiome shift by statistically noticeably reducing aRSVs belonging to genera containing disease-associated species, e.g., Porphyromonas, Tannerella, Treponema, and Aggregatibacter, and by noticeably increasing genera containing health-associated species. Mechanical therapy alone did not statistically noticeably affect any disease-associated taxa. Despite the difference in microbiome modulation both therapies improved the tested clinical parameters after two months. These results cast doubt on the relevance of the elimination and/or reduction of disease-associated taxa as a main goal of periodontal therapy.
Highlights
The oral cavity provides a unique eco-system with different niches for microbial organisms harboring a diverse microbiota with approximately 700 different prokaryote species [1]
Out of 192 samples initially processed from patients suffering from chronic periodontitis 24 samples did not satisfy quality criteria
The related 7 paired samples were excluded from further analysis, so that 178 samples from 47 placebo and 42 antibiotic patients remained for statistical analysis
Summary
The oral cavity provides a unique eco-system with different niches for microbial organisms harboring a diverse microbiota with approximately 700 different prokaryote species [1]. These microbes live in the human hosts and play important roles in health and disease. A mutual dependence exists between the host and the microbiome. Perturbations in this equilibrium can lead to a dysbiosis and to a diseased host [2]. In case of the periodontium a dysbiosis of the complex subgingival microbiome leads to the formation of periodontal pockets and destruction of tooth supporting tissue in most cases without notification of the host. 50% of the adult population suffer from moderate or severe forms of periodontitis in the United States [3]
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