In recent years, intermittent fasting (IF), including periodic fasting and time-restricted feeding (TRF), has been increasingly suggested to constitute a promising treatment for cardiometabolic diseases (CMD). A deliberate daily pause in food consumption influences the gut microbiome and the host circadian clock, resulting in improved cardiometabolic health. Understanding the molecular mechanisms by which circadian host-microbiome interactions affect host metabolism and immunity may add a potentially important dimension to effective implementation of IF diets. In this review, we discuss emerging evidence potentially linking compositional and functional alterations of the gut microbiome with IF impacts on mammalian metabolism and risk of development of hypertension, type 2 diabetes (T2D), obesity, and their longterm micro-and macrovascular complications. We highlight the challenges and unknowns in causally linking diurnal bacterial signals with dietary cues and downstream metabolic consequences and means of harnessing these signals toward future microbiome integration into precision medicine.cardiometabolic disease, circadian rhythms, gut microbiome, intermittent fasting, timerestricted feeding
Highlights• Time-specific diet is a novel nutritional approach to prevent and treat cardiometabolic disease.• Feeding-fasting cycles shape gut microbial composition and metabolite production. These alterations may play a causative role in driving the cardiometabolic benefits of intermittent fasting.• Despite the impressive results in animals, human studies show contradicting results, possibly due to intraindividual variation involved in the hostmicrobiome response to diet.