The gut-heart axis: a correlation between Paneth cells’ dysfunction, microbiome dysbiosis, and cardiovascular diseases

Gut microbiota dysbiosis is characterized by an imbalance in the core microbial equilibrium, leading to changes in the homeostasis of the gastrointestinal tract (GIT) environment. As guardians of the gut microbiota, Paneth cells (PCs) secrete antimicrobial peptides (AMPs) and play a crucial role in maintaining gut integrity and innate immunity in the small intestine. The gut-heart axis has emerged as a critical mediator in cardiovascular disease (CVD) pathogenesis and has drawn significant attention. In this regard, the reciprocal relationship between gut dysbiosis and PC dysfunction has been proposed, which may contribute to a compromised gut barrier and increased systemic inflammation, one of the main drivers of CVD development. It is also well-established that dysfunctional PCs disrupt gut homeostasis and subsequently permit the translocation of pro-inflammatory metabolites like trimethylamine N-oxide (TMAO) while reducing protective short-chain fatty acids (SCFAs), which correlates with atherosclerosis, hypertension, and heart failure. A better understanding of the underlying mechanisms linking gut health, PCs function, and cardiovascular outcomes is warranted for developing novel gut-target therapies against major CVD risks. This review aimed to comprehensively discuss the predominant role of PCs in the gut-heart axis, some effective compounds on PC function and AMP modulation, and finally, a possible correlation between PC dysfunction and CVD pathogenesis, encouraging future research to further elucidate this crosstalk.