Since the turn of the 21st century, two advances in biology have revolutionized our thinking of human metabolism. First, is the in-depth characterization of a previously recognized, but hitherto poorly defined organ system, the gut microbiome. This microbial organ exquisitely interacts with the diet which greatly influences its metabolic functions to impact host metabolism through the production of small bioactive molecules that continuously enter the bloodstream to act at local and distant organ tissues. Equally important, the host metabolism can also modulate the gut microbiome setting up the two as intricate and well-suited partners. Second, is the recognition that most of the cells and organs of the body are dependent on circadian rhythms, systemic timekeepers that play a major role in regulating behavioural and physiological functions to manage energy balance. In conditions of metabolic health, circadian rhythms are the beat to which the two well-matched partners, microbes and metabolism, dance. When these partners are out of step or mismatched, negative consequences may develop that promote metabolic disturbances and disease. Thus, unravelling this complex choreography becomes key to understanding how to maintain metabolic health and to correct missteps that may lead to the development of conditions like diet-induced obesity.

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