Abstract
Recent years have brought interesting insights into the human gut microbiota and have highlighted its increasingly recognized impact on cardiovascular (CV) diseases, including heart failure (HF). Changes in composition of gut microbiota, called dysbiosis, can trigger systemic inflammation, which is known to be involved in the pathophysiology of HF. Trimethylamine N-oxide (TMAO), which is derived from gut microbiota metabolites of specific dietary nutrients, has emerged as a key contributor to cardiovascular disease pathogenesis. Elevated TMAO levels have been reported to be associated with poor outcomes in patients with both HF and chronic kidney disease (CKD). Dysbiosis of gut microbiota can contribute to higher levels of TMAO and the generation of uremic toxins, progressing to both HF and CKD. Therefore, this bidirectional relationship between HF and CKD through gut microbiota may be a novel therapeutic target for the cardiorenal syndrome. However, the mechanisms by which gut microbiota could influence the development of heart failure are still unknown, and there are still some questions regarding the causative effects of TMAO and the underlying mechanistic link that explains how TMAO might directly or indirectly promote CV diseases including HF. Further studies are warranted to clarify the function of TMAO on the pathophysiology of cardiorenal syndrome and the handling of TMAO levels by the kidneys.