Abstract 2034: Gut Microbial Markers Associated With Clinical Features Of Peripheral Artery Disease

Abstract

Introduction: The human gut microbiome and microbe-derived metabolites are known to be associated with cardiovascular disease. However, their associations with lower extremity peripheral artery disease (PAD) are not well understood. The goal of this study is to identify specific gut microbial markers associated with clinical features of PAD. Methods: Study participants aged ≥ 18 years with documented PAD and non-PAD controls were recruited from a single center and performed home fecal sample collection. Sample aliquots were stored at -80°C until DNA extraction and shotgun metagenome sequencing. Untargeted metabolite quantification was performed using nuclear magnetic resonance. Samples from participants on antibiotics were excluded. Raw paired end sequences were quality filtered using the KneadData pipeline followed by taxonomic annotation using Kraken2 against the UHGG database (v2.0.2) and species abundance estimation using Bracken. A species network was constructed with centered log-ratio transformed abundance data and statistical analyses were performed in R. Results: Among 115 study participants, 80 had PAD and 35 were non-PAD controls. Of those with PAD, 40 (50.0%) had chronic limb threatening ischemia (CLTI) and 39 (48.8%) had symptoms of claudication. There were significant differences in alpha and beta diversity between the claudication and CLTI subgroups but none between the non-PAD and PAD groups overall. There were multiple significantly differentially abundant microbial features in the PAD group compared to non-PAD controls, including species within the genera Blautia and Clostridium . Metabolite profiles were also significantly different between the PAD and non-PAD groups, including higher abundance of the short chain fatty acid butyrate in the non-PAD controls (p=0.02). Network analyses identified three clusters of species with higher relative abundance in the claudication group compared to the CLTI group, and members of these clusters included putative butyrate producers. Conclusions: We identified specific microbial and metabolomic patterns associated with the clinical presentation of PAD and highlight a potential role for microbially-mediated butyrate in disease state.