Integrative transcriptomics and metabolomics reveal Cry1-associated hepatic alterations and plasma essential fatty acids as biomarkers of residual circadian disruption post-sepsis.

BACKGROUND

Sepsis disrupts circadian rhythm, leaving lasting molecular traces and circadian insensitivity to jet lag even after acute phase recovery. However, the core mechanism and biomarkers of residual circadian dysfunction post-sepsis remain unclear, which hinders targeted interventions.

METHODS

Male mice were subjected to non-lethal LPS injection, and after 7 days of recovery, liver transcriptomics and plasma metabolomics were integrated. Behavioral, physiological, and molecular analyses were performed, with statistical tests including DESeq2, Student's t-test, MetaCycle, and ROC curve analysis.

RESULTS

Significant transcriptomic alterations were observed, most prominently at Zeitgeber time 21. Linoleic acid (LA) and alpha-linolenic acid (ALA) were identified as sampling-time-independent candidate biomarkers associated with post-sepsis circadian disruption. Exogenous supplementation of these two fatty acids shortened male mice's rhythm re-entrainment period.

CONCLUSIONS

This study identifies a hypothesized Cry1-essential fatty acid axis potentially contributing to post-sepsis circadian dysfunction based on multi-omics associations, providing novel biomarkers and a metabolic intervention strategy for detecting and treating circadian rhythm disorders in sepsis survivors.