Targeted curation of the gut microbial gene content modulating human cardiovascular disease
Mikayla BortoniD, Michael ShafferiD, David W HoytiD, Ruisheng Jiang, Jared EllenbogeniD, Samuel Owen PurvineiD, Carrie NicoraiD, Elizabeth EderiD, Allison R. WongiD, Alan George SmulianiD, Mary S. Weir LiptoniD, Joseph Adrian KrzyckiiD, Kelly C. WrightoniD
Abstract
Despite the promise of the gut microbiome to forecast human health, few studies expose the microbial functions underpinning such predictions. To comprehensively inventory gut microorganisms and their gene content that control trimethylamine induced cardiovascular disease, we mined over 200,000 gut-derived genomes from cultivated and uncultivated microbial lineages. Creating MAGICdb (Methylated Amine Gene Inventory of Catabolism database), we designated an atherosclerotic profile for 6,341 microbial genomes that encoded metabolisms associated with heart disease. We used MAGICdb to evaluate diverse human fecal metatranscriptome and metaproteome datasets, demonstrating how this resource eases the recovery of methylated amine gene content previously obscured in microbiome datasets. From the feces of healthy and diseased subjects, we show MAGICdb gene markers predicted cardiovascular disease as effectively as traditional blood diagnostics. This functional microbiome catalog is a public, exploitable resource, enabling a new era of microbiota-based therapeutics.
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