Table 2.

Microbial metabolite production by gut bacteria and associated signaling pathways in CVDs

Gut bacterial species	Microbial metabolites	Potential receptors and mechanistic pathways	Impact	Associated diseases	References
Increased Veillonella, Klebsiella, and Haemophilus	LPS↑	TLR4 activation → pro-inflammatory cytokine release	Promotes plaque formation and inflammation	Ischemic heart disease (IHD)	Liu et al.132
Decreased Roseburia and Eubacterium	SCFAs↓	Reduced butyrate production → impaired immunomodulation	Attenuated protective effect	Ischemic heart disease (IHD)	Jie et al.18
Increased Firmicutes/Proteobacteria	TMAO↑	Dietary choline/carnitine → microbial CutC/D enzymes → TMA → hepatic FMO3 oxidation → TMAO	Promotes endothelial dysfunction and thrombosis	Ischemic heart disease (IHD)	Tang et al.79
–	PAGln ↑	Phenylalanine → microbial fermentation → phenylacetylglutamine	Activates adrenergic receptors → platelet hyperreactivity	Ischemic heart disease (IHD)	Nemet et al.69
Increased Eubacterium rectale	TMAO ↑	TMAO inhibits mitochondrial FAO → impaired energy metabolism	Exacerbates ventricular remodeling and cardiac dysfunction	Heart Failure (HF)	Tang et al.133; Organ et al.134
Decreased Faecalibacterium	SCFAs (propionate/butyrate) ↓	SCFA-GPCR signaling → blood pressure regulation and cardiac repair	Diminished cardioprotective effects	Heart Failure (HF)	Hu et al.135
Increased Enterobacteriaceae	LPS ↑	Impaired gut barrier → systemic LPS translocation → inflammation	Promotes myocardial inflammation and injury	Heart Failure (HF)	Sandek et al.42
Increased Prevotella, and Klebsiella	TMAO ↑	TMAO activates PERK/ROS/CaMKII pathway in VSMCs → enhanced vasoconstriction	Aggravates Ang II-induced hypertension	Hypertension	Jiang et al.136
Decreased Roseburia, and Faecalibacterium	SCFAs (acetate) ↓	Acetate → OLFR78 receptor activation → suppresses renin secretion	Impaired blood pressure regulation	Hypertension	Pluznick et al.98
Increased Collinsella	TMAO ↑	TMAO upregulates macrophage CD36/SR-A1 → foam cell formation	Accelerates plaque progression	Atherosclerosis	Wang et al.23
Decreased Roseburia,and Eubacterium	SCFAs (propionate) ↓	Propionate → Treg/IL-10 induction → suppresses NPC1L1 → reduced cholesterol absorption	Attenuated anti-atherogenic effect	Atherosclerosis	Haghikia et al.92
Decreased Bacteroides, and Prevotella	Secondary bile acids ↑	Microbial 7α-dehydroxylation → FXR receptor activation	Dysregulated lipid metabolism	Atherosclerosis	Jonsson et al.137
–	TMAO ↑	TMAO upregulates ER stress pathways	Promotes VSMC apoptosis	Thoracic Aortic Dissection (TAD)	Huang et al.138
–	Indole-3-aldehyde (3-IAID)	Inhibits synthetic phenotype transition of VSMCs	Attenuates dissection progression	Thoracic Aortic Dissection (TAD)	Huang et al.139
Decreased Roseburia intestinalis	SCFAs (butyrate) ↓	Butyrate inhibits neutrophil NETosis → reduces inflammation	Diminished vascular protection	Abdominal Aortic Aneurysm (AAA)	Tian et al.140
–	TMAO ↑	Activates ER stress and apoptotic pathways in vascular wall	Promotes AAA formation	Abdominal Aortic Aneurysm (AAA)	Benson et al.141
Decreased Lachnospiraceae	SCFAs (butyrate/valerate) ↓	SCFAs modulate lymphocyte homeostasis → suppress ROS	Reduced cardioprotection	Doxorubicin Cardiotoxicity	Li et al.142
Enterococcus faecalis	TMAVA ↑	Inhibits BBOX → reduced carnitine synthesis → impaired mitochondrial FAO	Promotes hypertrophy	Cardiac Hypertrophy	Zhao et al.143
–	Succinate ↑	Activates cardiomyocyte GPR91 → MAPK/ERK pathway → pro-hypertrophic gene expression	Induces cardiomyocyte hypertrophy	Cardiac Hypertrophy	Aguiar et al.144