New data on the link between gut bacteria, melatonin, and the circadian clock

clock

Many living organisms have circadian rhythms—biological processes that oscillate in a pattern following a roughly 24-hour cycle. In humans, researchers have observed the rhythmic expression of ‘clock genes’, resulting in molecular changes in multiple body tissues; the entire process is coordinated by ‘pacemakers’ such as the brain’s hypothalamic suprachiasmatic nucleus.

In addition to regulating physiological processes, the host’s circadian clock appears to affect the gut microbiome on a daily time scale. Previous studies have indicated that disruption of the circadian clock, either through dietary restriction or phase shifting (in conditions simulating jet-lag), begets changes in the temporal distribution of gut bacteria. Yet it is not known what signals drive these changes in the gut microbiota.

A new study published in PLOS one, led by Dr. Vincent Cassone from the Department of Biology, University of Kentucky (USA), provided insights on how the host clock regulates the microbiome. Researchers found that a species of human gut bacteria, Enterobacter aerogenes, has its own circadian rhythm and responds to fluctuations in the hormone melatonin.

In the study, researchers first took a species of Enterobacter aerogenes (isolated from a human patient) and tested it in vitro in the presence of melatonin. Proliferation of E. aerogenes was more rapid when melatonin was present, and this phenomenon occurred in a dose-dependent fashion. The same effect was not observed when E. aerogenes was exposed to tryptophan, serotonin or N-acetylserotonin. Moreover, two other bacterial species that were tested (Klebsiella pneumoniae and Escherichia coli) did not exhibit this sensitivity to melatonin.

Other work has established that the cyanobacterium Synechococcus elongatus shows patterns of gene expression, photosynthesis, and nitrogen fixation on a circadian rhythm. So the next question the researchers addressed in the current study was whether E. aerogenes also had its own circadian rhythm. To test this, cultures of E. aerogenes were transformed to express luciferase (enzymes that produce bioluminescence). In vitro, these bacteria indeed showed circadian patterns of bioluminescence (in 31–44% of cultures) when they were maintained in conditions approximating human body temperatures. And while the circadian phases of peak bioluminescence were variable, the researchers found that adding melatonin caused the bacterial rhythms to synchronize.

This work indicates the circadian clock of the host may give out hormonal signals that elicit responses from the circadian clocks of commensal gut bacteria. Authors of the study concluded by saying, “the existence of a circadian rhythm within a commensal bacterium that responds to an endocrine signal that is regulated by the circadian mechanism of the host gives further credence to the concept of the microbiome as a ‘meta-organism'”. That is, some bacteria in the gut seem to collectively respond to host signals associated with the 24-hour oscillation of biological processes.

Researchers noted that the exact mechanisms accounting for the observed bacterial rhythms are still unknown, although some data point toward a mechanism involving melatonin and redox-state sensing. Further research in humans might confirm whether melatonin secreted into the gut lumen is a way for the host to communicate with—and coordinate with—commensal bacteria in the gut.

 

 

Reference:

Paulose JK, Wright JM, Patel AG, Cassone VM. Human Gut Bacteria Are Sensitive to Melatonin and Express Endogenous Circadian Rhythmicity. PLOS one. 2016. http://dx.doi.org/10.1371/journal.pone.0146643

Kristina Campbell
Kristina Campbell
Science writer Kristina Campbell (M.Sc.), from British Columbia (Canada), specializes in communicating about the gut microbiota, digestive health, and nutrition. Author of the best selling Well-Fed Microbiome Cookbook, her freelance work has appeared in publications around the world. Kristina joined the Gut Microbiota for Health publishing team in 2014.  Find her on: GoogleTwitter