Effect of the Gut Microbiome on the Circadian Clock

Written by Rena Zhu and Edited by Kevin Liu

Sleep is an important part of our lives, where our bodies use this time period to repair cell damage and regulate levels of stress and growth hormones [1]. ‘Circadian rhythm’ is a popular term used to refer to and describe sleep cycles, which are “physical, mental, and behavioral changes that follow a daily cycle”, and is described as our internal molecular clocks [2]. Circadian rhythms differ per individual sleep patterns, which has made it hard to study previously. Disturbances in the environment, from exposure of artificial lighting to pulling all-nighters, can disrupt our internal molecular clocks.

Studies have shown that a large percentage of the human population is likely to experience circadian rhythm disruptions, especially older individuals [3]. The inability to fall asleep and maintain consistent sleep in older adults may be due to the increased prominence of neurologically damaging diseases such as Alzheimer’s or dementia in that population [4]. These diseases have been linked to an increase in arousal and awakening frequency, thus a reduction in total sleep time and quality [4]. Understanding how circadian rhythms work is a large contributor to decoding the puzzle of the older population’s sleep disruptions. Our internal clocks are not driven by when the sun rises and sets, but rather are synchronized to the daily 24-hour patterns of light and temperature produced by the earth’s rotation [5]. Not only that, circadian clocks regulate vast amounts of physiological processes, such as metabolism and the immune system [6]. A more indirect but impactful relation links the fundamental features of circadian cycles to the regulatory role of the gut microbiome.

New studies have shown a critical role of microbes in regulating health in its host through the expression of circadian genes, genes that code proteins necessary for the maintenance of the circadian clock [6]. When a gene is “expressed,” it is transformed by cell organelles into functional products like proteins. The expression of circadian genes in particular is powered by a feedback loop: a continuous output from the system that circulates back as input. The output of the loop promotes the expression of genes, which in return encourages circadian clock rates. This becomes a continuous cycle, creating an oscillating pattern of gene expression within the 24-hour period [7]. A 2017 study highlights that if there are alterations in the expression of circadian genes, this may result in the overproduction of corticosterone, which acts as a type of stress hormone in mice. An increase in the levels of corticosterone can lead to indications of diabetes [6]. The interactivity between diabetes and circadian clock genes is closely related, because diabetes is known to delay gastric emptying and impair colonic transit time, disruptions to the microbiome of the gut that are affected by the temperature and light fluxes of the environment [8]. In other words, it takes longer for food to travel from the stomach to the small intestine and stays in the large intestine for longer. In an individual with diabetes, these cycles do not synchronize with the 24 hour period, throwing both metabolism rates and the circadian rhythm cycle off. Although these results are produced using laboratory mice, researchers are hoping to extend this information to humans to better understand irregular sleep cycles through the use of the gut microbiome.

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