Host-microbiome Interactions in Apical Periodontitis: the Endodontic Microbiome in Relation to Circulatory Immunologic Markers.

AIM To explore microbial differences in the endodontic infection of teeth with primary and secondary apical periodontitis, with or without symptomatology. Additionally, to investigate if these differences are depicted in immunologic markers in blood. METHODOLOGY Twenty-nine teeth with primary or secondary apical periodontitis were extracted and cryo-pulverized. Blood was drawn from the subjects at three different timepoints before and three timepoints after the extraction in a time period of four months. The V4 hypervariable region of the 16S rRNA gene was sequenced using Illumina MiSeq. The microbiome profiles were ordinated using Principal Component Analysis and tested for differences between groups with permutational multivariate analysis of variance using the Bray-Curtis distance. If significantly different, the microbial profiles were further analyzed using the LDA effect size (LEfSe) biomarker discovery tool. A broad panel of inflammatory mediators in blood was examined longitudinally in all subjects during the six visits with mixed models. The Spearman correlation between these mediators and the zOTUs was calculated, significant correlations (p<0.05) were used as input for significant analysis of microarrays (SAM) using MeV. RESULTS After subsampling, the 467 zOTUs were classified into 9 phyla and 99 genera or higher-level taxa. The predominant genus in the entire sample set was Fusobacterium with a relative abundance of 12.3%, followed by Prevotella (9.9%), Actinomyces (7.7%), and Streptococcus (6.7%). The microbiomes of the endodontic infections were significantly associated with endodontic status (primary/secondary infection) (p=0.015) as well as with the presence or absence of pain (p=0.011). There was also a difference in the concentration of inflammatory mediators, namely CRP, IL-8, IL-10, IL-12p70, RANKL and TNF-α, depending on the existence of pain. In addition, the presence of specific bacteria (zOTUs) was correlated, positively or negatively, with the expression of several circulating inflammatory markers. CONCLUSIONS The microbial profiles and the concentration-time relationship of systemic inflammatory mediators of primary endodontic infection differed from those of secondary, and of symptomatic from those of asymptomatic cases. The fingerprint of associations between the immunological and microbiological profiles differed between of asymptomatic and symptomatic patients.