Intermittent fasting contributes to aligned circadian rhythms through interactions with the gut microbiome

The timing of food consumption is considered to be an important modulator of circadian rhythms, regulating a wide range of physiological processes which are vital to human health. The exact mechanisms underlying this relationship are not fully understood, but likely involve alterations in the structure and functioning of the gut microbiome. Therefore, this narrative review aims to clarify these mechanisms by focusing on intermittent fasting as a dietary strategy of food timing. A literature search identified 4 clinical and 18 preclinical studies that examined either (1) the impact of intermittent fasting on the gut microbiome, or (2) whether circadian rhythms of the host are subject to changes in the bacterial populations in the gut. Results reveal that intermittent fasting directly influences the gut microbiome by amplifying diurnal fluctuations in bacterial abundance and metabolic activity. This in turn leads to fluctuations in the levels of microbial components (lipopolysaccharide) and metabolites (short-chain fatty acids, bile acids, and tryptophan derivates) that act as signalling molecules to the peripheral and central clocks of the host. Binding of these substrates to pattern-recognition receptors on the surface of intestinal epithelial cells in an oscillating manner leads to fluctuations in the expression of circadian genes and their transcription factors involved in various metabolic processes. Intermittent fasting thus contributes to circadian rhythmicity in the host and could hold promising implications for the treatment and prevention of diseases associated with disordered circadian rhythms, such as obesity and metabolic syndrome. Future intervention studies are needed to find more evidence on this relationship in humans, as well as to clarify the optimal fasting regimen for balanced circadian rhythms.