Structural changes in the gut virome of patients with atherosclerotic cardiovascular disease

Abstract

ABSTRACT The gut microbiota is an important risk factor and therapeutic target in atherosclerotic cardiovascular disease (ACVD), a leading cause of morbidity and mortality worldwide. However, alterations in the gut viral community and its contribution to ACVD have rarely been investigated. In this study, we characterized and compared the gut viromes from the fecal metagenomes of 214 patients with ACVD and 171 healthy individuals using a reference-dependent virome approach. We revealed that ACVD patients exhibited a significant increase in viral richness at the family level and a visible alteration in overall virome structure regardless of host sex, age, or body mass index. At the viral operational taxonomic unit (vOTU) level, we identified 105 vOTUs that significantly increased in abundance in ACVD patients and 60 vOTUs that increased in abundance in healthy controls. A majority (43.8%) of the ACVD-enriched vOTUs were predicted to infect Streptococcaceae, Lachnospiraceae, Ruminococcaceae, and Enterobacteriaceae, and Streptococcaceae had tight correlations with the corresponding gut bacterial species, whereas a considerable proportion (35.0%) of the control-enriched vOTUs were Bacteroidaceae, Burkholderiaceae, and Lachnospiraceae phages. Functional analyses revealed five viral auxiliary metabolic genes that differed in frequency between ACVD-enriched and control-enriched vOTUs. Moreover, we identified gut viral signatures for ACVD discrimination and achieved an optimal area under the receiver operator characteristic curve of 0.878 for distinguishing patients from healthy controls. Our results provide a comprehensive view of the ACVD gut virome, which may contribute to the development of novel diagnostic and therapeutic strategies for ACVD and additional relevant cardiovascular diseases. IMPORTANCE Existing studies have found that there is a close relationship between human virome and numerous diseases, and diseases may affect the diversity and composition of the virome; at the same time, changes in the virome will in turn affect the onset and progression of the disease. However, the composition and functional capabilities of the gut virome associated with atherosclerotic cardiovascular disease (ACVD) have not been systematically investigated. To our knowledge, this is the first study investigating the gut virome in patients with ACVD. We characterized the structural changes in the gut virome of ACVD patients, which may facilitate additional mechanistic, diagnostic, and interventional studies of ACVD and related diseases.

Keywords

• gut virome
• atherosclerotic cardiovascular disease
• viral function
• viral auxiliary metabolic genes
• fecal metagenome sequencing
• gut bacteriome