An unrecognized host response to microbial exposure resets circadian timing.

Apr 27, 2026bioRxiv : the preprint server for biology

A hidden body response to microbes may reset daily biological clocks

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Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Microbes can reset mammalian cellular clocks and influence plant and algal rhythms.

Evolutionarily diverse microbes have the ability to drive phase shifts in circadian rhythms across different kingdoms.
In mammals, soluble components from bacteria can increase levels of the protein PER2 without requiring new transcription.
The p38 MAPK pathway is identified as a potential modulator of the circadian response to bacterial exposure.
These findings suggest that bacterial exposure may serve as a novel input to circadian clocks, influencing biological timing.

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As ubiquitous features of every natural environment, microbes have profoundly shaped eukaryotic biology throughout evolution. Circadian clocks evolved in all domains of life as central regulators that align physiology with environmental cycles, yet whether they respond directly to microbial signals remains unknown. Here, we demonstrate that evolutionarily diverse microbes potently reset mammalian cellular clocks and can drive phase shifts in plants and algae, indicating cross-kingdom effects of microbes on circadian rhythms. In mammals, exposure to soluble bacterial components distinct from canonical innate immune ligands induces acute PER2 upregulation independently ofor nascent transcription. A targeted inhibitor screen and biochemical assays implicate p38 MAPK as a modulator of this response. Taken together, this positions bacterial exposure as a previously unrecognized circadian clock input, revealing a new axis of host-microbe interaction that modulates biological timing at the cellular level. Bmal1