Long-term changes in the subgingival microbiota in patients with stage III-IV periodontitis treated by mechanical therapy and adjunctive systemic antibiotics: A secondary analysis of a randomized controlled trial.

AIM: To explore whether adjunctive antibiotics can relevantly influence long-term microbiota changes in stage III-IV periodontitis patients. MATERIALS AND METHODS: This is a secondary analysis of a randomized clinical trial on periodontal therapy with adjunctive 500 mg amoxicillin and 400 mg metronidazole or placebo thrice daily for 7 days. Subgingival plaque samples were taken before and 2, 8, 14 and 26 months after mechanical therapy. The V4-hypervariable region of the 16S rRNA gene was sequenced with Illumina MiSeq 250 base pair paired-end reads. Changes at the ribosomal sequence variant (RSV) level, diversity and subgingival-microbial dysbiosis index (SMDI) were explored with a negative binomial regression model and non-parametric tests. RESULTS: Overall, 50.2% of all raw reads summed up to 72 RSVs (3.0%) that were generated from 163 stage III-IV periodontitis patients. Of those, 16 RSVs, including Porphyromonas gingivalis, Tannerella forsythia and Aggregatibacter actinomycetemcomitans, changed significantly over 26 months because of adjunctive systemic antibiotics. SMDI decreased significantly more in the antibiotic group at all timepoints, whereas the 2-month differences in alpha and beta diversity between groups were not significant at 8 and 14 months, respectively. CONCLUSIONS: Mechanical periodontal therapy with adjunctive antibiotics induced a relevant and long-term sustainable change towards an oral microbiome more associated with oral health.

Effect of periodontal therapy on adipokine biomarkers in overweight.

AIM: The aim of this study was to evaluate the effect of non-surgical periodontal therapy on circulating levels of the systemic inflammation-associated biomarkers orosomucoid (ORM), high-sensitivity C-reactive protein (hsCRP), chemerin, and retinol-binding protein 4 (RBP4) in overweight or normal-weight patients with periodontitis at 27.5 months after therapy. MATERIALS AND METHODS: This exploratory subanalysis includes patients from the ABPARO-trial (ClinicalTrials.gov NCT00707369). The per-protocol collective provided untreated periodontitis patients with high (≥28 kg/m2 ) or moderate (21-24 kg/m2 ) BMI. Out of the per-protocol collective, 80 patients were randomly selected and stratified for BMI group, sex, and treatment group (antibiotics/placebo), resulting in 40 overweight and normal-weight patients. Patients received non-surgical periodontal therapy and maintenance at 3-month intervals. Plasma samples from baseline and 27.5 months following initial treatment were used to measure the concentrations of ORM, hsCRP, chemerin, and RBP4. RESULTS: At the 27.5-month examination, ORM and hsCRP decreased noticeably in the overweight group (ORM: p = .001, hsCRP: p = .004) and normal-weight patients (ORM: p = .007, hsCRP: p < .001). Chemerin decreased in the overweight group (p = .048), and RBP4 concentrations remained stable. CONCLUSION: Non-surgical periodontal therapy reduced systemically elevated inflammation-associated biomarkers in periodontitis patients. These improvements were more pronounced in overweight patients than in normal-weight patients.

Significant Short-Term Shifts in the Microbiomes of Smokers With Periodontitis After Periodontal Therapy With Amoxicillin & Metronidazole as Revealed by 16S rDNA Amplicon Next Generation Sequencing.

The aim of this follow-up study was, to compare the effects of mechanical periodontal therapy with or without adjunctive amoxicillin and metronidazole on the subgingival microbiome of smokers with periodontitis using 16S rDNA amplicon next generation sequencing. Fifty-four periodontitis patients that smoke received either non-surgical periodontal therapy with adjunctive amoxicillin and metronidazole (n = 27) or with placebos (n = 27). Subgingival plaque samples were taken before and two months after therapy. Bacterial genomic DNA was isolated and the V4 hypervariable region of the bacterial 16S rRNA genes was amplified. Up to 96 libraries were normalized and pooled for Illumina MiSeq paired-end sequencing with almost fully overlapping 250 base pairs reads. Exact ribosomal sequence variants (RSVs) were inferred with DADA2. Microbial diversity and changes on the genus and RSV level were analyzed with non-parametric tests and a negative binomial regression model, respectively. Before therapy, the demographic, clinical, and microbial parameters were not significantly different between the placebo and antibiotic groups. Two months after the therapy, clinical parameters improved and there was a significantly increased dissimilarity of microbiomes between the two groups. In the antibiotic group, there was a significant reduction of genera classified as Porphyromonas, Tannerella, and Treponema, and 22 other genera also decreased significantly, while Selenomonas, Capnocytophaga, Actinomycetes, and five other genera significantly increased. In the placebo group, however, there was not a significant decrease in periodontal pathogens after therapy and only five other genera decreased, while Veillonella and nine other genera increased. We conclude that in periodontitis patients who smoke, microbial shifts occurred two months after periodontal therapy with either antibiotics or placebo, but genera including periodontal pathogens decreased significantly only with adjunctive antibiotics.