## 4 Interaction Between the Gut Microbiota and Cardiovascular Diseases  
The gastrointestinal system is considered to be the largest endocrine organ in the human body due to its ability to produce a wide range of bioactive metabolites, such as SCFAs, TMA--which is converted by hepatic FMO3 into TMAO--secondary bile acids (e.g., deoxycholic acid, lithocholic acid), and tryptophan-derived indices. These compounds can either be metabolised by the host's enzymes, such as sulfotransferases, monooxigenases, or conjugating enzymes, into signalling molecules, or directly act as such [135]. For instance, SCFAs act via G protein-coupled receptors (e.g., GPR41 and GPR43), while indole derivatives modulate the aryl hydrocarbon receptor (AhR) pathway [135, 136, 137, 138]. These molecules are absorbed by the intestinal epithelium through various mechanisms, including passive diffusion (e.g., for lipophilic bile acids), active transport (e.g., via monocarboxylate transporters for SCFAs), and carrier-mediated uptake. Upon entering the bloodstream, they can exert effects on various organs and systems, thereby influence multiple host metabolic pathways [135].  
Shifts in microbial composition, characterised by an increased abundance of pro-inflammatory taxa, such as members of the _Enterobacteriaceae_ family (including _Escherichia Shigella_), _Desulfovibrio_ spp., _Collinsella_ spp., _Eggerthella_ spp., and _Streptococcus_ spp., along with a depletion of beneficial butyrate-producing genera, such as _Faecalibacterium prausnitzii_, _Roseburria_ spp., _Subdoligranulum_ spp., and _Eubacterium rectale_, have been strongly associated with the pathogenesis of CVDs. These alterations are frequently accompanied by reduced microbial diversity and changes in the relative proportions of dominant bacterial phyla. In particular, shifts in the _Bacilita_/_Bacteroidota_ ratio have been linked to metabolic disturbances, such as increased energy harvest, low-grade inflammation, and adiposity, which collectively contribute to cardiovascular risk. Although some studies report a higher _Bacilita_/_Bacteroidota_ ratio in obese and hypertensive individuals, findings are not universally consistent, highlighting the complexity of microbiota-host interactions in CVD development. Conversely, protective genera, such as _Akkermansia_, _Blautia_, and _Lactobacillus_, are often depleted in individuals with CVD. Such compositional shifts may modulate cardiovascular risk by influencing lipid metabolism, gut barrier integrity, immune activation, and the production of bioactive metabolites like TMAO, ultimately contributing to vascular dysfunction and atherogenesis [90]. Furthermore, bacterial components, such as lipopolysaccharide-acrylamide (LPS), a constituent of the outer membrane of Gram-negative bacteria, can trigger immune activation via the NF-kB pathway, promoting foam cell formation and atherogenesis [135; 139]. The accompanying endothelial dysfunction, aggravated by elevated levels of ROS, further amplifies vascular inflammation, contributing to plaque formation and thrombosis [135].  
While bacterial-derived metabolites have been extensively studied in the context of atherosclerosis, emerging evidence suggests that other non-bacterial components of the gut microbiota, including fungi, viruses, and bacteriophages, may also contribute to cardiovascular pathology, albeit through distinct mechanisms [140; 141; 16; 20].