The Influence of Tryptophan Derivatives and AhR on Circadian Rhythmicity

Abstract

The patterned expression of clock genes across a 24-hour day-night cycle makes up an organism’s circadian rhythm. This circadian clock influences the expression of a plethora of genes that modulates behavior, metabolism, and immune defense mechanisms across many organisms. Similarly, the microbiome—a vast population of microorganisms living in our gut—is also actively involved in metabolism and immune function. However, the specifics of coordinated signaling between the circadian clock and microbiome as it pertains to metabolic function remain unclear. This study investigates if a class of microbial metabolites, tryptophan derivatives, can directly influence circadian clock function through mice small intestinal organoid culture. Through circadian bioluminescence assays, I found that indoles influence the amplitude of the Per2 bioluminescent rhythms, which serves as a proxy for the circadian clock, in a dose-dependent manner. Though gene expression analysis confirmed activation of the aryl hydrocarbon receptor (AhR) pathway with metabolite addition, Per2 modulation occurs independently of AhR signaling. Together, these results support a role for microbial metabolites the bidirectional communication between the gut microbiome and host intestinal clock.