Gut microbiota, lifestyle, and atherosclerosis: unravelling microbial contributions to cardiovascular risk

The gut microbiota has emerged as a compelling area of investigation as a potential and unconventional contributor to cardiovascular diseases (CVDs).Improving our understanding of the gut microbiota's role in CV events is crucial for advancing current risk stratification strategies. We analyzed data from the CV-PREVITAL study, a multicentre, prospective, open-label interventional RCT designed to compare the effectiveness of a mobile health intervention versus usual care in reducing CV risk in Italian patients, over the age of 45.Our local cohort enrolled 1043subjects.Data collected included:a)clinical assessments (traditional risk factors, Doppler ultrasound of carotid and femoral arteries, detailed medical history);b)Pittsburgh Sleep Quality Index, to assess sleep disturbances. c)Healthy Lifestyle Score (0–6), with scores >3 indicating a healthy lifestyle and ≤3 an unhealthy lifestyle. d)Alpha and Beta diversity analysis was performed in 500subjects and adjusted for all variables that may influence microbiota composition:the taxonomic composition was analyzed with MetaPhlAn 4, while HUMAnN 3.9 was used to process all samples. 652species-level genome bins were identified, along with 3,384,536 UniRef90 gene families and 523metabolic pathways.Alpha diversity was evaluated based on SGB richness,Shannon and Simpson indices.Beta diversity was assessed using Bray-Curtis and Jaccard distances. Alpha diversity analysis revealed no significant differences between patients with or without subclinical atherosclerosis (ASCVD).Beta diversity analysis showed that microbial composition differed based on lifestyle and the specific vascular site affected by atherosclerosis.Notably, F. prausnitzii and S. isoflavoniconvertens were more common in ASCVD patients with a healthy lifestyle and A. hadrus was enriched in controls with a healthy lifestyle.SGB15213 and SGB4597 were found in controls with unhealthy lifestyles.Regarding location-specific differences, in ASCVD patients with a healthy lifestyle: S. thermophilus, B. faecalis, and H. filiformis were dominant in femoral atherosclerosis, whereas L. asaccharolyticus and O. valericigenes were more prevalent in carotid atherosclerosis.In ASCVD patients with an unhealthy lifestyle: SGB6579 and SGB14137 were associated with femoral atherosclerosis;Collinsella SGB14754 was linked to both femoral and carotid atherosclerosis. Our findings reveal significant differences in microbiome composition between patients with and without subclinical ASCVD. The higher prevalence of F. prausnitzii and S. isoflavoniconvertens in ASCVD patients with a healthy lifestyle raises questions about their potential role in disease predisposition.Conversely, the association of SGB15213 and SGB4597 with unhealthy lifestyle in subjects without ASCVD suggests they may have a protective effect.These results highlight the need for further research into the microbiota’s role in atherosclerosis pathogenesis and its potential as a predictive biomarker.