Multi-omics integration reveals functional signatures of gut microbiome in atherosclerosis
Abstract
ABSTRACT Atherosclerosis (AS), a predominant contributor to global cardiovascular disease burden, exhibits complex interplay with gut microbiota dysbiosis. While the associations between microbial imbalance and AS pathogenesis are well-documented, the pathophysiological mechanisms governing microbe-host crosstalk remain incompletely characterized. Current research limitations stem from methodological heterogeneity across studies and the absence of consensus regarding disease-specific microbial signatures. In this study, we conducted an integrated multi-omics analysis to characterize the functional signatures of gut microbiome in AS. We collected all public AS-related 6 microbiome datasets and 8 peripheral blood host transcriptomic datasets from across the world, comprising 456 metagenomic samples and 111 16S rRNA gene sequencing samples for microbial profiling, alongside 118 RNA-Seq samples and 302 microarray samples. We systematically characterized AS microbial taxa and computationally inferred the metabolic potential for the gut microbiome using metabolomic-related data. Metabolite-host gene interactions were further predicted based on the synergistic effects between microbiome and host transcriptome in AS. Five “microbe-metabolite-host gene” tripartite associations related to AS were identified involving 5 microbial genera (Actinomyces, Bacteroides, Eisenbergiella, Gemella, and Veillonella), 2 metabolites (Ethanol and H2O2), and 2 host genes (FANCD2 and GPX2), and the…
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