Do we treat our patients or rather periodontal microbes with adjunctive antibiotics in periodontal therapy? A 16S rDNA microbial community analysis

• Published in: PloS one Vol. 13; no. 4; p. e0195534
• Main Authors: Hagenfeld, Daniel, Koch, Raphael, Jünemann, Sebastian, Prior, Karola, Harks, Inga, Eickholz, Peter, Hoffmann, Thomas, Kim, Ti-Sun, Kocher, Thomas, Meyle, Jörg, Kaner, Doğan, Schlagenhauf, Ulrich, Ehmke, Benjamin, Harmsen, Dag
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18-04-2018; Public Library of Science (PLoS)
• Subjects: Adult; Amoxicillin; Amoxicillin - pharmacology; Amoxicillin - therapeutic use; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Antibiotics; Associated species; Base pairs; Biodiversity; Biology and Life Sciences; Bleeding; Care and treatment; Chronic Periodontitis - drug therapy; Chronic Periodontitis - microbiology; Computer and Information Sciences; Dentistry; DNA, Ribosomal; Ecology and Environmental Sciences; Female; Genera; Genomes; Gingiva - microbiology; Gum disease; Health aspects; Hospitals; Humans; Koch, Sebastian; Male; Medical research; Medicine and Health Sciences; Metronidazole; Metronidazole - pharmacology; Metronidazole - therapeutic use; Microbiomes; Microbiota; Microbiota - drug effects; Microbiota - genetics; Microorganisms; Middle Aged; Pathogens; Patients; Periodontal diseases; Periodontitis; Regression analysis; Regression models; Research and analysis methods; Ribosomal DNA; rRNA 16S; Samples; Smoking; Statistical analysis; Statistical methods; Studies; Taxa; Therapy; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0195534

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.