Circadian Rhythms Regulated By Gut Microbiome

Even the microbes living inside you have a daily routine. They start their day like clockwork, in one part of the intestinal lining, move a few micrometers to the left, maybe the right, and then return to their original position.

Diverse communities of microbes live in and on us in astounding numbers. Scientists now estimate that a typical human body is made up of about 30 trillion human cells and 39 trillion bacteria.

New research in mice now reveals that the regular timing of these small movements can influence a host animal’s circadian rhythms by exposing gut tissue to different microbes and their metabolites as the day goes by. Disruption of this dance can affect the host.

Eran Elinav, an immunologist at the Weizmann Institute of Science, who led the work with co-senior author Eran Segal, a computational biologist also at the Weizmann, says:

“This research highlights how interconnected the behavior is between prokaryotes and eukaryotes, between mammalian organisms and the microbes that live inside them. These groups interact with and are affected by each other in a way that can’t be separated.”

Biological Clockwork

Previous work by Elinav and Segal revealed that our biological clocks work in tandem with the biological clocks in our microbiota and that disrupting sleep-wake patterns and feeding times in mice induced changes in the microbiome in the gut.

Their new study had three major findings.

First of all, the microbiome on the surface layer of the gut undergoes rhythmical changes in its “bio-geographical” localization throughout the day and night. So the surface cells are exposed to different numbers and different species of bacteria over the course of a day.

“This tango between the two partners adds mechanistic insight into this relationship,” Elinav says.

Secondly, the circadian changes of the gut microbiome have profound effects on host physiology, and unexpectedly, they affect tissue that is far away from the gut, such as the liver, whose gene expression changes in tandem with the gut microbiome rhythmicity.

“As such,” adds Elinav, “disturbances in the rhythmic microbiome result in impairment in vital diurnal liver functions such as drug metabolism and detoxification.”

Finally, the circadian rhythm of the host is deeply dependent on the gut microbiota oscillations.

gutmicrobes

Thaiss et al/Cell 2016

Although some circadian machinery in the host was maintained by its own internal clock, other components of the circadian clock had their normal rhythms destroyed. Most surprising, another set of genes in the host that normally exhibit no circadian rhythms stepped in and took over after the microbial rhythms were disrupted.

Health Implications

The investigators say their work has potential implications for human health in two important ways.

Number one, because drugs ranging from acetaminophen to chemotherapy are metabolized in the liver, understanding, and potentially being able to manipulate, the circadian rhythms of our microbiota could affect how and when medications are administered.

Number two, understanding more about this relationship could help to eventually intervene in health problems like obesity and metabolic syndrome, which are more common in people whose circadian rhythms are frequently disrupted due to shift work or jet lag.

Thaiss, Christoph A. et al.
Microbiota Diurnal Rhythmicity Programs Host Transcriptome Oscillations
Cell , Volume 167 , Issue 6 , 1495 – 1510.e12

Top Image: Darryl Leja, National Human Genome Research Institute, National Institutes of Health, CC BY-NC

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