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Figure 5. Dysbiosis in aging and AF. Aging-associated dysbiosis causes gut barrier impairment and an imbalance in gut microbe-derived metabolites, which causes increased levels of circulating lipopolysaccharide (LPS). LPS stimulates the secretion of inflammatory cytokines and activates the NLRP3 inflammasome in aged atria, exacerbating atrial fibrosis. This inflammatory environment facilitates the formation of fibrosis, leading to slowed conduction and reentrant arrhythmias. Inflammation in AF can also aggravate dysbiosis by disrupting gut microbiota balance, which worsens gut dysbiosis and perpetuates inflammation in the heart. Notably, NLRP3 inhibitor MCC950 has been shown to decrease fibrosis in atria and reduce AF susceptibility. The figure was generated with BioRender.com.