Decoding the gut microbiota-mitochondrial-inflammasome axis in cardiovascular disease

The inter-disciplinary relationship between the gut microbiota, mitochondrial function, and inflammation activation represents a frontier in understanding Cardiovascular complications. This comprehensive review provides a framework of the signalling networks that link these three biological systems and their collective impact on cardiovascular disease. The gut microbiota is a diverse ecological community comprising bacterial phyla, including Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria, which contribute to the functions of distal organs by producing bioactive metabolites. We systematically examined how microbial dysbiosis participates in inflammasome and mitochondrial-derived cardiovascular pathophysiology. This review also provides insight into various molecular pathways (TLR, PI3K/AKT, JAK/STAT, MAPK, TRPV, CREB, TXNIP, YAP, MyD88 and NLRP3) and therapeutic interventions targeting this axis, including gut microbiota modulation agents, mitochondrial-targeted antioxidants, and inflammasome inhibitors, offering mechanistic insights into their cardioprotective effects. Using current evidence and data from PubMed, Google Scholar, Web of Science, and ResearchGate, we provide a mechanistic understanding of the gut microbiota-mitochondria-inflammasome axis. This triad represents a critical target in cardiovascular health and warrants new diagnostic and therapeutic strategies.