*4.2. Gut Microbiota and Atherosclerosis*

Atherosclerosis is a chronic inflammatory condition characterized by a lipid core and an outer fibrous cap that mostly affects the middle and major arteries. A substantial cause of mortality, atherosclerosis is an immunoinflammatory condition that results in blockages in the large and medium arteries and acute CVD [90]. The presence of bacteria in the atherosclerotic plaques of patients with coronary artery disease was confirmed by fluorescence in situ hybridization and conserved polymerase chain reaction [91]. Macrogenomic sequencing of the feces of the subjects was performed in a case-control study of 218 patients with atherosclerotic cardiovascular disease (ACVD) and 187 healthy controls. This study found increased copy numbers of bacterial genes encoding TMA lytic enzymes (enzymes associated with TMAO production), increased TMAO production, and increased abundance of the atherosclerotic cardiovascular disease (ACVD) gut microbiome comprising *Enterobacteriaceae* and *Streptococcus*, among other significant metabolic alterations functionally associated with ASCVD [92]. New approaches for the identification and management of atherosclerosis may emerge from the study of gut microbiota and its metabolites. Dietary factors and gut flora are strongly linked to the development of atherosclerosis, with inflammation also playing a role. For instance, an increase in *Bacteroides fragilis* resulted in a decrease in *Lactobacilli* and an increase in *Desulfovibrionaceae*, which caused dysfunctional lipid or glucose metabolism and worsened the inflammatory response [93]. Peanut skin extract reduced the serum total and low-density lipoprotein cholesterol content, and increased the high-density lipoprotein cholesterol content in atherosclerotic mice, thereby decreasing the development of atheromatous plaques [94].

Dysbiotic intestinal flora can worsen cardiovascular diseases. Through altered gut microbiota composition, immune cell activation, and metabolic dysfunction, an imbalance in the gut microbiota caused by poor diet, aging, and antibiotic usage might exacerbate cardiovascular diseases. Disruption of the gut microbiota may, in turn, be further promoted by cardiovascular disorders (Figure 2). A balanced gut microbiota may prevent the progression of CVD.

**Figure 2.** Crosstalk between cardiovascular disease and gut microbiota. Various microbes in the gut are represented with different colors. (This Schematic representation was created using Biorender (https://biorender.com/)).
