The microbiome interacts with the circadian clock and dietary composition to regulate metabolite cycling in the gut

ABSTRACT: Gut microbiomes play a key role in the maintenance of host metabolic homeostasis and health. An important aspect of metabolism is its circadian regulation, but how the microbiome regulates metabolite cycling under different conditions, including variations in dietary composition, remains undefined. In this study, we utilized high temporal resolution metabolite profiling of the Drosophila gut to investigate the role of the microbiome in metabolite cycling. We find that, in contrast to its effect on transcript cycling, the microbiome increases metabolite cycling in the gut. In the absence of a circadian clock, the microbiome has minimal effect on the number of metabolites cycling, but profoundly affects phase, suggesting that the clock stabilizes circadian phase in the face of microbial changes. Interestingly, the impact of the microbiome is also reduced in a timed feeding paradigm, and vice versa, suggesting that timed feeding and the microbiome have similar circadian effects. Finally, the microbiome increases metabolite cycling but does not alter phase in flies fed high protein diets, but suppresses metabolite cycling and changes cycling phase in flies fed high sugar diets. Enrichment analysis of cycling metabolites found that amino acid metabolism is particularly sensitive to changes in the microbiome, the circadian clock and timed feeding. Collectively, our observations highlight a key role of the microbiome in producing robust metabolite cycling, in conjunction with the circadian clock and dietary composition.

INSTRUMENT(S): Liquid Chromatography MS - positive, Liquid Chromatography MS - negative, Gas Chromatography MS -

PROVIDER: MTBLS8819 | MetaboLights | 2025-04-08

REPOSITORIES: MetaboLights