THU0514 ROLE OF THE ORAL MICROBIOME IN CHRONIC NON-BACTERIAL OSTEOMYELITIS IN CHILDREN
Authors: Mona Zeus, Stefan Janssen, Ute Fischer, Hans Jürgen Laws, Arndt Borkhardt, Prasad Oommen
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Chronic non-bacterial osteomyelitis (CNO) is a rare autoinflammatory disease of the bone and bone marrow. The presentation of the disease is broad, but pain and osteoedema on MRI are the hallmarks of CNO. While the activation of inflammasomes and the subsequent release of IL-1ß seems to play a central role, the exact molecular pathophysiology of CNO is largely unexplained. In respect of the potential role of the microbiome to date only experimental data on mice are available, indicating that the manipulation of the microbiome through dietary modulation might alter the course of the disease and also plays a role in the release of IL-1ß from innate immune cells<sup>1</sup>. <h3>Objectives</h3> To identify the impact of the oral microbiome on CNO in children and adolescents. Dysbiosis as a state of pathological alteration of the microbiome has been discussed as an environmental factor in rheumatic diseases in adults and in children<sup>2</sup>. Human data in CNO are lacking. <h3>Methods</h3> 20 patients (12 male and 8 female, aged 3 to 13 years) with a median of 10.3 years were examined. Two different sites of the oral cavity (center and left part of the tongue) were swabbed. In total, 143 individual samples were retrieved and subjected to 16s r-RNA amplicon sequencing: DNA was extracted using the QIAamp® DNA Microbiome Kit. The V4 region of the 16S ribosomal RNA gene was amplified by PCR with V4 specific primers. A limited‐cycle amplification step was performed. Libraries were normalized and pooled, and sequenced on a MiSeq system (Illumina). Raw sequence reads were demultiplexed and clustered into sub-OTUs (operational taxonomic units) via Deblur in Qiita. Qiime2 was used to calculate alpha- and beta- diversity for multiple alternative metrics. Statistical significance was calculated with non-parametric tests (Mann-Whitney and Permanova). <h3>Results</h3> The administration of medication in general (mostly NSAIDs) had a significant impact on the microbiome (p-value &lt; 0.02). With limited statistical power of the small cohort, gender, age and disease activity do not significantly influence the microbiome. There is a significant difference between the variable swab sites at the 1% level (p&lt;0.01). Whereas swabs from the center of the tongue exhibit more Streptococci salivarius, the left outer part of the tongue shows more Haemophilus parainfluenza. <h3>Conclusion</h3> To the best of our knowledge, this is the first study of the oral microbiome in children and adolescents in CNO. Our data suggests that administration of medication to CNO patients alters the microbiome. It is also influenced by a change of the swab site. Limited patient numbers did not allow to show an effect on disease activity, but enrollment will continue. <h3>References</h3> [1] Lukens JR, Gurung P, Vogel P, Johnson GR, Carter RA, McGoldrick DJ et al. Dietary modulation of the microbiome affects autoinflammatory disease. Nature 2014; 516: 246-249. [2] Verwoerd A, Ter Haar NM, de Roock S, Vastert SH, Bogartt D. The human microbiome and juvenile idiopathic arthritis. Pediatric Rheumatology 2016 Sep 20; 14(1):55 <h3>Disclosure of Interests</h3> None declared