Circadian clocks in the brain-rectum axis regulate the rhythmic production of sex pheromones originating from rectal bacteria

Abstract Studies have shown that intestinal bacteria have profound effects on the neurophysiological development of their hosts via the gut-brain axis. However, it is still unclear whether and how host neurophysiological activities can affect the activity of intestinal bacteria. Here, we examined the molecular basis for the rhythmic production of sex pheromones by rectal bacteria in flies and demonstrated that a series of genes in the brain-rectum axis were activated for rhythmic production of sex pheromones. By comparative transcriptome analysis, we identified clock genes (cryptochrome 1 (CRY1), timeless (TIM) and pigment-dispersing factor (PDF)) in the brain-rectum axis and showed that genetic silencing of these genes abolished the rhythmic production of sex pheromones. Moreover, we identified the genes downstream (glycine N-methyltransferase (GNMT) and alpha-galactosidase (GLA)) of the clock genes and showed that they are responsible for producing rectal glucose and glycine (or threonine), which are the precursors of bacteria-originated sex pheromones. Together, these findings reveal distinct genes and targets that lie in the brain-rectum axis as a fundamental conduit for the rhythmical production of sex pheromones by rectal bacteria.