A sizable percentage of the population stands to benefit from elucidating mechanisms linking sleep loss, circadian misalignment, and metabolic disease. In particular, shift work is associated with increased risk for metabolic diseases, including type 2 diabetes, obesity, and metabolic syndrome [1]. These workers also report less sleep per day, and often outside of the biological night. While a reflexive instinct to these discoveries is to encourage more sleep, this may not always be practical for shift working individuals. In light of inevitable sleep loss and circadian misalignment associated with these work patterns comes a need for suitable therapeutic targets to support better long-term health outcomes. In a recent issue of Molecular Metabolism, Benedict and colleagues [2] provide the first published insights into the relationship between sleep and gut microbiota in human subjects. Their study provides a novel consideration of acute sleep restriction and the gut microbiota and opens an important discussion of future investigations of the gut microbiota in human sleep research.