Background and Aims

Gut Microbiota (GM) alterations in composition associate with cardiovascular disease (CVD) via multiple cellular and immune-inflammatory networks. We performed GM analysis in a cohort of the general population, to relate intestinal bacterial landscape and functionality to Subclinical Carotid Atherosclerosis (SCA).

Methods

GM composition of 345 subjects from an epidemiological study at low CVD SCORE risk was assessed by fecal genomic DNA extraction and 16S rRNA gene sequencing. In a representative subset 23 subject free from SCA and in 23 subjects with advanced SCA, a further GM analysis by whole metagenomic shotgun sequencing (WMSS) predicted cellular and metabolic pathways expressed in each bacterial strain.

Results

GM was correlated with CVD risk and circulating inflammatory markers. We highlighted different GM landscape in individuals with or without SCA (p=0.016). Reduction of Bacteroides and significant increase of pro-inflammatory genera Escherichia, Coriobacteriaceae and Streptococcus was observed, while reduction of anti-inflammatory Roseburia, Bifidobacterium, Faecalibacterium in subjects with SCA was outlined.

WMSS added higher abundance of further pro-inflammatory Dorea, Granulicatella, Klebsiella and Citrobacter strains associated to advanced SCA. The functional metagenomic data analysis revealed specific metabolic pathways upregulated with SCA (metabolism of sugars and arginine on top) and those with absence of SCA (purines synthesis and starch degradation).

Conclusions

We provided new and specific signatures of GM dysbiosis marking SCA in a general population at low CVD risk. The metagenomic functional analysis identified bacterial strains responsible of the metabolic and functional dysbiosis associated with SCA.