The gut microbiome is closely interconnected with the host physiology. Evidence continues to mount that the cardiovascular (CV) system, although seemingly distant from the gut, is also influenced by the gut microbiota. Sitting at the interface between the host and the environment, the gut microbiome mediates and modulates ways in which the environment affects CV risk and progression of cardiovascular disease (CVD), including heart failure (HF). One of the chief mechanisms involves microbially produced small molecules that act at or beyond the host gut barrier. Biological processes dysregulated in HF, such as myocardial energetics, cardiac remodeling, and repair capacity, systemic vascular and inflammatory tone, are some of the processes affected by metabolites produced by our gut microbiome, including short-chain fatty acids, trimethylamine-N-oxide, indole-3-propionate, and phenacetylglutamine. Several of these are direct metabolites of nutrients we consume daily, and this represents one of the mechanisms by which our diet may modify CV risk. In this issue of JACC: Heart Failure, Molinaro et al[1] offer the first evidence for another microbially produced metabolite with potential relevance for CV and HF pathophysiology.
The study by Molinaro et al[1]focused on imidazole propionate (ImP), a gut microbial metabolite of the amino acid histidine. Having previously found circulating ImP to be elevated in patients with type 2 diabetes (T2D)
