Abstract 639: Lung Microbiome Dysbiosis in Schistosomiasis-associated Pulmonary Arterial Hypertension

Introduction: Pulmonary arterial hypertension (PAH) is a life-threatening inflammatory cardiopulmonary disease with no cure. Infection by the intravascular parasite Schistosoma mansoni recapitulates several aspects of widespread inflammation that leads to PAH (Sch-PAH).After infection, the S. mansoni eggs cross the gut wall, disturbing its microbiome; however, it remains unknown whether their translocation into the lungs also disturbs the lung microbiome, leading to PAH. Hypotheses: We hypothesize that S. mansoni eggs disturb the lung microbiome contributing to vascular inflammation and PAH. Methods: To test this hypothesis, we induced Sch-PAH in end-Scl.cre ERT2 ;Rosa mt/mg mice by intraperitoneal sensibilization with 240 eggs/grambody weight (bw; 2 weeks) followed by intravenous injection of 175 eggs/gram bw. After 7 days, lungs were used for microbiome analysis by shotgun metagenomics and data aligned with OneCodex Microbiome Database. Results: Metagenomic analysis revealed that S. mansoni infection disrupts the lung microbiome (Shannon Diversity Index: 1.5 +/- 0.07 and 1.18 +/- 0.07, control and infected, respectively; n = 5 mice/group). At the Phylum level, analysis indicated that infection reduced Firmicutes and Bacteroidetes while it also increased Euryarchaeota in the control group. Preliminary data showed that Firmicutes reduction was higher in infected females compared tomales (Mean reads: 0.0891 and 0.0126, respectively; reads normalized by the top 5% lungmicrobiota). Finally, principal coordinate analysis (PCoA) identified a distance in the clustering pattern between sexes, which may account for microbiome differences in Sch-PAH. Conclusion: To our knowledge, this is the first report on lung microbiome dysbiosis during murine Sch-PAH. Understanding whether the lung microbiome contributes to Sch-PAH or protects its host opens a novel therapeutic direction for treatment of pulmonary infectious vascular diseases.