Abstract
BACKGROUND: Obesity is widely recognized as an aggravating risk factor for atherosclerosis (AS), yet the effects of obesity on AS-associated microbiome dysbiosis are not sufficiently characterized. This study aims to identify the contribution of obesity-related dysbiosis in AS. METHODS: Using shotgun metagenomic sequencing, we studied gut microbiome composition and functional capacity across non-obese AS patients (AS-NOB, BMI < 30, n = 93), age-sex-matched non-obese controls (Ctrl-NOB, BMI < 30, n = 27), and obese AS patients (AS-OB, BMI ≥ 30, n = 68). RESULTS: Gut community composition differed significantly across study groups (PERMANOVA F = 3.23, p = 0.001). Among metadata, obesity had the strongest effect (F = 3.1, p < 0.01) on the microbiome structure of AS patients. Furthermore, obese AS patients demonstrated a decrease in species richness and evenness (p < 0.05). Taxonomic and functional analysis further suggested that obesity does not simply aggravate AS-associated gut dysbiosis but instead redirects it towards a distinct community state, characterized by a Prevotella expansion that consistently opposes the rest of the bacterial community. Among AS microbiome markers, an increase was detected in Pseudomonadota (Proteobacteria), Bilophila, Dysosmobacter, and Faecalibacterium. CONCLUSION: Taken together, these results suggest that pathological expansion of Prevotella, potentially in conjunction with reduced alpha diversity, may represent a putative indicator of increased risk in AS patients, particularly within populations where the Prevotella enterotype or subtype is prevalent, warranting further investigation.