Multi-Omics Profiling Identifies a Cry1-Essential Fatty Acid Axis Driving Residual Circadian Rhythm Dysfunction After Sepsis Recovery

Sepsis disrupts circadian rhythm and leaves lasting molecular traces, rendering the clock insensitive to jet lag even after recovery from the acute phase. Here, we employed a comprehensive multi-omics approach, integrating liver transcriptomics with plasma metabolomics, to characterize the residual molecular signatures in male mice following recovery from a non-lethal dose of LPS for 7 days. Our results revealed significant transcriptomic alterations, most prominently at Zeitgeber time 21 (ZT21), which may be regulated by the core clock gene Cry1. Furthermore, linoleic acid and alpha- linolenic acid were identified as potential biomarkers of circadian rhythm disruption, independent of sampling time. These findings offer novel candidate biomarkers with potential utility in the detection and therapeutic monitoring of circadian rhythm disorders following sepsis recovery.