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

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.

Two-sample Mendelian randomization to study the causal association between gut microbiota and atherosclerosis

“…Correlation analysis showed that enterococcus, streptococcus and ruminococcus were widely associated with viral operational taxonomic unit in patients with cardiovascular disease. This also reflects the fact that enteroviruses affect disease by relying on gut bacteria (47). In summary, we found that there may be a complex network among gut microbes, with interactions among bacteria, viruses, and fungi that jointly affect the occurrence and development of atherosclerosis.…”

“…As far as we know, bacteria are a major component of the gut microbiome, but viruses, fungi, and archaea are also present, they live symbiotic in our gut. Although intestinal flora plays an important role in atherosclerosis, enteroviruses, fungi and their metabolites are also involved in the development of atherosclerosis (46,47). First of all, the gut microbiota of adults is mainly composed of five phyla: Bacteroidetes, Firmicutes, Actinobacteria, Proteobacteria, and Cerrucomicrobia (48), and changes in the components of these flora can cause ecological imbalance of intestinal flora.…”

Gut microbiota’s causative relationship with peripheral artery disease: a Mendelian randomization study

“…While bacteria are the primary components of the gut microbiome, other symbionts like viruses, fungi, and archaea also play significant roles. Recent studies ( Chen et al, 2023 ; Li et al, 2024 ) have suggested a link between viruses and the incidence of atherosclerotic diseases, indicating that other components of the human symbiotic microbial system, beyond bacteria, may have associations with PAD that warrant further investigation. Our current analysis focuses solely on the correlation between the gut microbiota and PAD, leaving the relationships between other components of the human symbiotic microbial system and PAD to be explored in future research.…”

Distinct characteristics of the gut virome in patients with osteoarthritis and gouty arthritis

“…Using VLP-based metagenomic sequencing, we enhanced the detection of previously missed viral diversity and species, and shed light on the interplay between gut viruses and bacteria. A notable finding was the increased proportion of Microviridae, which predominantly target Gram-negative bacteria [ 40 ], and has been implicated in various conditions, including IBD, irritable bowel syndrome (IBS), and coronary heart disease [ 41 – 44 ]. Our results suggested an elevated prevalence of Microviridae in arthritis patients, deviating from typical stool virome.…”