Summary: Researchers report our gut bacteria is sensitive to melatonin and expresses its own circadian rhythm.

Source: University of Kentucky.

The circadian rhythm, or circadian clock, is an internal mechanism that drives the 24-hour cycles that tell our bodies when to sleep, wake and eat — and now, new research has found that bacteria living within the gut also have a clock.

“We are the directors of that clock, much like the sun directs our own circadian rhythms!” said Jiffin Paulose, UK post-doctoral scholar and co-author of the study in PLOS ONE.

Paulose and Professor and Chair of the Department of Biology Vincent Cassone found that a certain class of bacteria found in the human gut, Enterobacter aerogenes, expresses circadian patterns because of its sensitivity to melatonin, the hormone produced at night and stimulating sleep.

While melatonin is made by the pineal gland, a small gland in the brain, it is also present throughout the gastrointestinal (GI) system. In addition, many foods contain melatonin. The GI system’s circadian clock is coordinated to both light and the timing of eating.

Paulose said the effect of melatonin on this bacterium is remarkable: when exposed to melatonin at levels similar to those found in the gut, the individual cells begin to communicate with each other and coordinate periods of swimming and dividing in a phenomenon known as swarming.

“This swarming in the presence of melatonin occurs every 24 hours and keyed us toward finding the circadian clock,” he said.

This is the first demonstration of a circadian clock in a prokaryote outside the phylum Cyanobacteria, and the researchers’ findings suggest that the cyanobacterial and E. aerogenes clocks share common evolutionary ancestors.

“If our future work demonstrates this is true, then the evolution of circadian organization predates the emergence of oxygen generating photosynthesis some 3.5 billion years ago,” Cassone said.

Their findings also point to the overall circadian organization in vertebrates as being an arrangement of multiple circadian pacemakers organized in a hierarchical system of clocks. Paulose said now they must consider the bacteria that coexist within the body as part of that hierarchy.

“Not only are we sending signals (like melatonin) to the bacteria in our guts, mouths, skin, etc., but they are also sending signals back that affect us; from the molecular level all the way up to our behavior,” he said. “The biological and clinical significance of this grand scale of circadian coordination will be important to discover in the very near future.”

Source: Whitney Harder – University of Kentucky
Image Source: This NeuroscienceNews.com image is credited to Jiffin Paulose.
Original Research: Full open access research for “Human Gut Bacteria Are Sensitive to Melatonin and Express Endogenous Circadian Rhythmicity” by Jiffin K. Paulose, John M. Wright, Akruti G Patel, and Vincent M. Cassone in PLOS ONE. Published online July 11 2016 doi:10.1371/journal.pone.0146643

Abstract

Human Gut Bacteria Are Sensitive to Melatonin and Express Endogenous Circadian Rhythmicity

Circadian rhythms are fundamental properties of most eukaryotes, but evidence of biological clocks that drive these rhythms in prokaryotes has been restricted to Cyanobacteria. In vertebrates, the gastrointestinal system expresses circadian patterns of gene expression, motility and secretion in vivo and in vitro, and recent studies suggest that the enteric microbiome is regulated by the host’s circadian clock. However, it is not clear how the host’s clock regulates the microbiome. Here, we demonstrate at least one species of commensal bacterium from the human gastrointestinal system, Enterobacter aerogenes, is sensitive to the neurohormone melatonin, which is secreted into the gastrointestinal lumen, and expresses circadian patterns of swarming and motility. Melatonin specifically increases the magnitude of swarming in cultures of E. aerogenes, but not in Escherichia coli or Klebsiella pneumoniae. The swarming appears to occur daily, and transformation of E. aerogenes with a flagellar motor-protein driven lux plasmid confirms a temperature-compensated circadian rhythm of luciferase activity, which is synchronized in the presence of melatonin. Altogether, these data demonstrate a circadian clock in a non-cyanobacterial prokaryote and suggest the human circadian system may regulate its microbiome through the entrainment of bacterial clocks.

“Human Gut Bacteria Are Sensitive to Melatonin and Express Endogenous Circadian Rhythmicity” by Jiffin K. Paulose, John M. Wright, Akruti G Patel, and Vincent M. Cassone in PLOS ONE. Published online July 11 2016 doi:10.1371/journal.pone.0146643