Microbiological researchNov 1, 2025

Disrupted daily rhythms harm gut mucus and immune balance through changes in gut bacteria caused by sebacic acid

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 27, 2026

Abstract

Essence

Circadian rhythm disturbance was linked to sebacic acid-driven gut dysbiosis, mucus-barrier impairment, immune activation, and intestinal inflammation.

Evidence

A mixed translational study profiled intestinal metabolites in individuals with shift work disorder and tested sebacic acid, gut bacteria, immune responses, and CYP4A inhibition in circadian-disturbance models.

Caveat

The mechanistic and inhibitor findings do not yet show that targeting sebacic acid or CYP4A improves digestive disease outcomes in shift workers.

Simplified

Circadian rhythm disturbance caused by shift work has become increasingly prevalent, emerging as a risk factor for digestive diseases. Both the host's and the microbial metabolic pathways and functions might be markedly altered by circadian disruption. However, metabolic changes in the gut during shift work are poorly reported. Here, we demonstrated intestinal metabolome signatures in individuals with shift work disorder and identified sebacic acid as a symptoms-related metabolite. Shift work-related circadian rhythm disturbance leads to enhanced hepatic fatty acid ω-oxidation and a significant increase in dicarboxylic fatty acids in feces. Among these, the increased sebacic acid impaired the intestinal mucus barrier by regulating composition of mucus-related gut bacteria, characterized by an increase in Muribaculaceae and a decrease in Akkermansia abundance, along with activated immune system characterized by increased B cell responses, thereby driving the occurrence of intestinal inflammation. The application of the inhibitor for CYP4A, a key ω-hydroxylase in fatty acid oxidation, effectively improved intestinal dysfunction caused by circadian rhythm disturbance. Our findings provide a deep insight into understanding the role of circadian rhythm in maintaining intestinal homeostasis.