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

Abstract

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.

Circadian Rhythms in Gastrointestinal Health and Diseases

“…A potential role for gut-secreted melatonin in passing circadian timing cues from host to commensal bacteria was presented by Jiffin Paulose from Dr. Cassone’s laboratory. Melatonin increased motility and swarming in Enterobacter aerogenes, an effect that is at least partially mediated by melatonin receptors 11 .…”

Sleepy, circadian disrupted and sick: Could intestinal microbiota play an important role in shift worker health?

“…Another is to request a routine sample at a prescribed time of day – an option which preliminary work in our laboratory indicates is feasible [ unpublished data ]. The frequency and timing of collection is especially important in light of recent findings suggesting diurnal rhythms in certain gut microbes, and sensitivity to melatonin [6]. Future studies will need to determine the sensitivity of samples to time of day in order to establish best practice in timing and frequency of sample collection.…”

Circadian Rhythm Shapes the Gut Microbiota Affecting Host Radiosensitivity

“…Then, 16S RNA sequencing revealed that, compared with the 12 h dark/12 h light cohort, there were much fewer observed species of enteric bacteria in the other two groups (Figure 1E). Given that gut microbiota is sensitive to melatonin [14], we assesses the expression of Mtnr1a and Mtnr1b , the receptors of melatonin, at different circadian times. Intriguingly, the expression of Mtnr1a and Mtnr1b was different among the three cohorts (Figure 1F,G), suggesting that the alteration of intestinal microbiota might depend on circadian rhythm-shaped expression of Mtnr1a and Mtnr1b .…”