Illuminating gut microbiome signaling pathways that regulate host circadian rhythms
The gut microbiome affects host physiology by modulating nutrient acquisition and creating chemical signals that are received by host receptors. The molecular details of the orchestration of these microbial signaling processes remain largely unclear. We used a function-centric approach to interrogate the mechanistic links between gut microbiome metabolism and host circadian rhythms. We used rodent models, including germ-free mice, to determine how the gut microbiome influences host chronobiology by assaying metabolites in the gut and in circulation, and we used activity-based protein profiling to provide direct functional links to individual taxa. We specifically investigated how externally imposed behavioral schedules, such as feeding schedules, can desynchronize biological rhythms in metabolic organs (e.g., the gut, pancreas, and liver) from the central circadian rhythms regulated by the brain. We hypothesize that the gut microbiome creates chemical signals that can be entrained by feeding/fasting schedule to induce internal metabolic misalignment. Elaborating on the findings of this project will elucidate the chemical signals from the microbiome that modulate biological rhythms in the host’s metabolic organs.