Metabolic reconstitution by a gnotobiotic microbiota varies over the circadian cycle

The capacity of the intestinal microbiota to degrade otherwise indigestible diet components is known to greatly improve the recovery of energy from food. OligoMM12-colonized gnotobiotic mice have a consistently higher fat-mass than germ-free or fully colonized counterparts. We investigated their food intake, digestion efficiency, energy expenditure and respiratory quotient using a novel isolator-housed metabolic cage system. Intriguingly, the respiratory exchange ratio of OligoMM12-colonized gnotobiotic mice phenocopied fully colonized mice during the dark (active/eating) phase but phenocopied germ-free mice during the light (fasting/resting) phase. Furthermore, OligoMM12-colonized mice showed a germ-free-like drop in liver glycogen storage during the light cycle and both liver and plasma metabolomes of OligoMM12 mice clustered closely with germ-free mice. 16S amplicon sequencing was used to show that these differences throughout the circadian cycle are not associated with any changes in community composition. This implies the absence of microbiota functions in the OligoMM12 consortium that are required to maintain normal host metabolism during the resting/fasting phase of circadian cycle.