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Contribution of the endogenous circadian clock to diurnal rhythms in the microbiome of the gut and mouth in humans


EMSL Project ID
60571

Abstract

The gut microbiome, the community of commensal, symbiotic, and pathogenic microorganisms in our intestines, are integral for the host’s digestion and metabolic function, and resistance to infection. Considerations of the bidirectional communication between the brain and the microbiome of the gut (microbiota-gut-brain-axis) have led to a number of studies over the last decade that also link gut microbiota diversity with neurological and psychiatric disorders via a range of possible direct and indirect communication pathways (e.g., neurotransmitters synthesized by the microbiota). This bidirectional communication is posited as a potential mechanism by which interactions between the host’s circadian clock and oscillations of microbiota populations regulate physiological and behavioral processes in the host such as regulation of the endocrine system and sleep. To this extent a number of studies have reported diurnal oscillations of gut microbiota in mice. Knockout of core clock genes that orchestrate circadian rhythms in cells throughout the body, reduces the diurnal oscillations of gut microbiota compared to wild-type mice. These knockout studies suggest the importance of circadian rhythmicity for regular microbiota function; however, it is likely that the loss of rhythm in these studies can be contributed to disrupted feeding behaviors as time-restricted feeding or fasting is sufficient to restore rhythmicity. Beyond the timing or even the type of food consumed, sleep quality and duration, and perturbations to the endocrine system (e.g., acute stress), have all been noted to alter the diversity of gut microbiota. Thus, in order to examine the contribution of the circadian system to diurnal oscillations of the microbiota in humans, Dr. Bowles at OHSU will use an intensive multiday protocol where sleep-wake cycles are adjusted so all behaviors occur evenly across all circadian phases while in a constant environment including dim light (to avoid light resetting circadian phase). This protocol allows separation of clock driven circadian rhythms from diurnal variability that may be secondary to behavior. To generate a spread of bowel movements across the circadian clock from which to measure the microbiota, samples will be collected from 4 different participants. Additionally, while the microbiota of the oral cavity has been studied to a lesser extent, it provides an additional opportunity to access the host’s circadian regulation. Saliva can also be more readily collected at equal frequencies across all study participants. Analyses of both matrices will allow us to measure overlap between the behavior of the two ecosystems of bacteria (in relation to the host’s circadian rhythm).

Project Details

Start Date
2022-08-30
End Date
N/A
Status
Active

Team

Principal Investigator

Sneha Couvillion
Institution
Pacific Northwest National Laboratory

Team Members

Josie Hansen
Institution
Pacific Northwest National Laboratory