Gut microbiota metabolism may be responsible for various biomarkers that interact with nutrients in the pathogenesis of cardiovascular diseases (CVDs). Recent studies show that a human gut microbial gene catalogue also exists in the body, which appears to be established by metagenomics sequencing. The gut microbiome develops a plastic endocrine organ that integrates input cues from the diet and interfaces with the host to play a role in the pathogenesis of CVD and metabolic disorders through various mechanisms. There is evidence that diverse components within our diet, such as macronutrients, micronutrients, symbionts, pathogens, among others, can participate in meta-organismal (microbe to host) signaling pathways to promote or prevent against CVD risk. Further studies indicate that microbial communities resident in the human gastrointestinal tract play major roles in harvesting energy from our food and serve as a key endocrine organ secreting metabolites that act as hormone-like factors that are sensed by dedicated receptor systems in the human host. Gut microbes can also signal to the host to regulate innate immunity through metabolism-independent pathways, where constituents of the microbial cell wall are sensed by host cells, through pattern recognition receptors (PRR) to further impact CVD progression. © Nova Science Publishers, Inc.