56 - METAGENOMIC SEQUENCING OF MUCOSAL SAMPLES ASSOCIATES ABIOTROPHIA DEFECTIVA, LAUROTROPIA MIRABILIS AND ROTHIA DENTOCARIOSA WITH KAWASAKI DISEASE

Background: Epidemiological and clinical features suggest that Kawasaki Disease (KD) is triggered by an airborne transmissible agent. Despite dedicated investigations spanning more than five decades, the underlying cause of KD continues to elude definitive identification.

   Study Question: Can metagenomic sequencing of nasopharyngeal samples from children with KD and febrile controls identify a causative pathogen which may not have been identified by previous culture-based methods?

   Methods: DNA was extracted from throat swabs collected from 116 children diagnosed with KD and 105 febrile controls. Sequencing was performed using an Illumina HiSeq 4000 instrument. To categorize the obtained reads, alignment was conducted against a custom-designed database that encompassed sequences from human genomics, bacteria, archaea, viruses, and fungi. Given the inherent challenge of limited bacterial biomass in the oropharynx and the relatively higher presence of human DNA in KD samples, a multifaceted approach was employed to identify organism enriched in KD vs febrile controls.

   Results: Comparison of the relative abundance of bacteria between the KD and febrile control groups identified 13 taxa that significantly exhibited enrichment in KD. Of these, Abiotrophia defectiva, Rothia Dentocariosa and Lautropia mirabillis were consistently associated with KD in sensitivity analyses. These organisms increased in prevalence in the first two years of life but had a greater abundance in the KD group when compared to the febrile control group (All three produced a strong association p< 0.001 and an area under the receiver operating curve of 0.65). 

   Conclusions: Our finding of an increased abundance of A. defectiva, L. mirabillis and R. Dentocariosa in the oropharyngeal microbiome of KD suggests that these bacteria might trigger KD in young children at a time when tooth eruption or viral coinfection might damage the oral mucosa to increase interaction of the bacterial microbiome with the immune system of young children.