Late Breaking Abstract - Transkingdom circadian orchestration of host and airway microbiota in chronic pulmonary inflammation

<bold>Background:</bold> There exists a bidirectional circadian interaction between host and gut microbiota which modulates intestinal inflammation. Yet little is known about the rhythmicity of airway microbiota and its relationship with lung clock and inflammation. <bold>Methods:</bold> A murine model of chronic pulmonary inflammation was made by intranasal challenge with elastase (ELT) and LPS for 4w. Mice were sampled every 6hr over a day. Lung tissue was used for 16S sequencing and detection of clock gene expression by qPCR and WB. Bronchioalveolar lavage (BAL) was collected for inflammatory cell counting. <bold>Results:</bold> We detected significant diurnal fluctuations in alpha diversity (Shannon, Evenness and Sobs indices) of airway microbiota in naïve mice, which peaked at ZT 0, 12 and 24. By taxonomical analysis, we found the rhythmic oscillation of airway microbiota was largely attributed to a highly abundant genera (54%), <italic>Achromobacter</italic>, which exhibited a nearly antiphase rhythm to alpha diversity. After repetitive elastase/LPS challenge, the rhythmic oscillation of airway microbiota underwent adaptive changes, featured by significant decrease in alpha diversity and increase in <italic>Achromobacter</italic> abundance at ZT0/24. Interestingly, the abnormal oscillations of core clock genes (BMAL1 and CLOCK) of the lung in ELT/LPS-treated mice were also marked by their significant decrease at ZT0/24 compared to naïve mice. Concomitantly, BAL inflammatory cells especially neutrophils in ELT/LPS-treated vs. naïve mice showed the largest increase at ZT0/24. <bold>Conclusion:</bold> Airway microbiota exerts active diurnal oscillations with significant disturbances in the inflamed lung accompanied by synchronized host circadian disruption.