bioRxiv : the preprint server for biologyApr 27, 2026

A hidden body response to microbes may reset daily biological clocks

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 27, 2026

Abstract

Essence

Microbial exposure can reset biological clocks across diverse systems and induces a mammalian PER2 response linked to p38 MAPK.

Evidence

This laboratory cross-kingdom study tested evolutionarily diverse microbes in mammalian cellular clocks, plants, and algae, with inhibitor screening and biochemical assays for the mammalian response.

Caveat

The mechanistic evidence centers on cellular and experimental exposure systems, not organism-level disease or natural microbial environments.

Simplified

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