The Gut Microbiota-NLRP3 Inflammasome Axis in Chronic Heart Failure: Mechanisms Across Heart Failure Phenotypes and...

Chronic heart failure (CHF) patients often suffer from intestinal microbiome dysbiosis and persistent systemic inflammation, forming a vicious cycle that current therapies struggle to effectively disrupt. The NLRP3 inflammasome, a key component of the innate immune system, is abnormally activated in CHF and closely associated with myocardial fibrosis, ventricular remodeling, and deteriorating cardiac function. Recent advances in the "gut-heart axis" theory have revealed widespread gut microbiota imbalance and intestinal barrier dysfunction in CHF patients, with microbial-derived metabolites influencing cardiovascular homeostasis through multiple pathways. However, the mechanistic interplay between the NLRP3 inflammasome and gut microbiota in CHF, subtype-specific regulatory networks across different forms of heart failure, and the translational potential of interventions targeting this axis remain incompletely integrated. This narrative review aims to systematically summarize the tripartite axis of "gut microbiota-NLRP3 inflammasome-chronic heart failure." Literature was retrieved from PubMed, Web of Science, and the China National Knowledge Infrastructure (CNKI) databases between 2017 and 2026, including reviews, original research, and preclinical studies. Most available evidence comes from basic science and animal experiments, resulting in significant heterogeneity; clinical studies are limited and predominantly observational association analyses, leading to overall low-level evidence. Moreover, most therapeutic data-such as drug inhibition, dietary, and microbiome-based interventions-are derived from preclinical models, with insufficient large-scale, multicenter prospective intervention trials to confirm their efficacy and safety, necessitating further validation in humans. By summarizing the structure, function, and activation mechanisms of the NLRP3 inflammasome, analyzing the regulatory roles of gut microbiota and their metabolites in CHF, outlining the characteristics of this axis across different heart failure subtypes and reviewing emerging therapeutic strategies targeting NLRP3, this review seeks to address existing knowledge gaps and provide theoretical foundations and new research directions for precision prevention and treatment of heart failure.