Continuous Light-Induced Circadian Rhythm Disruption Impairs Intestinal Barrier Integrity in Male C57BL/6 Mice Through Gut Microbiota Dysbiosis and the Apoptosis-Inflammation-Oxidative Stress Cascade
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Background
Circadian rhythm disruption (CRD) is a risk factor for irritable bowel syndrome (IBS), but the mechanism linking CRD to intestinal barrier dysfunction remains unclear. This preclinical study aimed to clarify whether CRD impairs intestinal barrier integrity via gut microbiota dysbiosis and the “apoptosis-inflammation-oxidative stress” cascade.
Methods
Twenty-four male C57BL/6 mice were randomized into control (12h light/dark, n=12) and CRD (21-day continuous light, n=12) groups. Circadian disruption was verified via locomotor activity, serum melatonin/serotonin, and clock gene expression. Intestinal barrier function, microbiota, apoptosis, inflammation, and oxidative stress were assessed using FITC-dextran permeability, 16S rRNA sequencing, Western blotting (WB), TUNEL, and ELISA.
Results
CRD increased intestinal permeability (+114.7%, p<0.001), shortened villi (−25.6%, p=0.018), downregulated tight junction proteins (ZO-1, Occludin, p<0.05), and altered microbiota (family-level: decreased Prevotellaceae, increased Bacteroidaceae, p<0.05). It also activated the apoptosis-inflammation-oxidative stress cascade (Caspase-3/β-actin: +1.4-fold, IL-1β: +44.1%, MDA: +50%, CAT: −90%, all p<0.05).
Conclusions
CRD impairs intestinal barrier integrity via gut microbiota dysbiosis and the apoptosis-inflammation-oxidative stress cascade. These preclinical findings identify gut microbiota and the apoptosis-inflammation-oxidative stress cascade as potential targets for further investigating IBS associated with CRD.
