Transkingdom Control of Microbiota Diurnal Oscillations Promotes Metabolic Homeostasis

The authors of this study demonstrate that there are significant bacterial species that contribute to the microbiota of the mammalian gut which are regulated by circadian principles.  By altering the timing of feeding, introducing circadian distortion by simulating jet lag in mice, or by using genetic mutants animals that lack critical components of the cellular circadian clock (PER1/2 knockout), the normal cyclical presence and activity of various microbes in the gut is altered.  The consequence of this disruption as studied in this work includes significant weight gain and glucose intolerance in test mice, a finding which is interestingly ablated by the administration of oral antibiotics.   As further evidence, the authors show replication of metabolic dysfunction when microbiota from human jet lagged subjects is transplanted into the gut of germ free mice under normal conditions indicating that this dysbiosis is not only persistent after jet lag but may be regulated by intrinsic principles in the microbial pool that are unaffected by an otherwise normally functioning host environment. In summary, this article demonstrates that circadian disruption causes dysbiosis of mammalian gut microbiota causing persistent deleterious metabolic changes and may be amenable to simple therapeutic interventions.