An unrecognized host response to microbial exposure resets circadian timing

Area of Science:

• Microbiology
• Chronobiology
• Molecular Biology

Background:

• Microbes are essential in natural environments and have shaped eukaryotic evolution.
• Circadian clocks regulate physiology according to environmental cycles across all life domains.
• The direct impact of microbial signals on circadian clocks is not well understood.

Purpose of the Study:

• To investigate whether microbial signals directly affect circadian clocks.
• To explore cross-kingdom effects of microbes on biological timing.
• To identify molecular mechanisms underlying microbial influence on mammalian circadian clocks.

Main Methods:

• Exposure of mammalian cells, plants, and algae to diverse microbes and bacterial components.
• Analysis of PER2 and Bmal1 expression.
• p38 MAPK inhibitor screening and biochemical assays.

Main Results:

• Diverse microbes reset mammalian cellular clocks and induce phase shifts in plants and algae.
• Soluble bacterial components, not canonical immune ligands, acutely upregulate PER2 in mammals.
• This upregulation occurs independently of Bmal1 and nascent transcription.
• p38 MAPK is implicated as a key modulator of the response.

Conclusions:

• Microbial exposure is a novel input for circadian clocks.
• This study uncovers a new host-microbe interaction axis influencing cellular biological timing.
• Microbial signals exert cross-kingdom effects on circadian rhythms.