Long-term microbiota changes with antibiotics
Aim:    To explore whether adjunctive the use of adjunctive500mg amoxicillin and 400mg metronidazole thrice daily for 7 days can relevantly influence long-term microbial microbiota changes in stage III-IV periodontitis patientsusing 16S rRNA gene sequencing.   Materials and Methods:    This is a secondary analysis of subgingival plaque samples from a randomized clinical trial aboutNon-smoking and smoking periodontitis patients (n=163, ABPARO-cohort, Clinicaltrials.gov NCT00707369) received periodontal therapy with adjunctive amoxicillin/metronidazole or placebo and were followed upbefore, 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 on 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, 72 RSVs (3.0%) summed up to 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 differently over time 26 months because of adjunctive systemic antibiotics. Porphyromonas gingivalis, Tannerella forsythia and Aggregatibacter actinomycetemcomitans decreased significantly stronger and more sustainably in the antibiotic group. Many other RSVs, including health associated species, increased again after 2-months in both groups. The SMDI significantly enhanced decreased significantly more in the antibiotic-groupthe antibiotic group  at all timepointsup to 26 months, whereas the 2-month differences in alpha and beta diversity between groups were not significant anymore at 8 and 14 months, respectively.