Curcumin Alleviates Systemic Inflammation and Gut Dysbiosis Induced by Circadian Rhythm Disruption in a Rodent Model of Jet Lag

Abstract

Circadian rhythm disruption is increasingly recognized as a systemic stressor that promotes immune dysregulation and gut microbial imbalance, processes implicated in a wide range of inflammatory and neurodegenerative diseases. However, therapeutic strategies targeting the gut-immune interface under conditions of circadian misalignment remain limited. Here, we investigated whether curcumin, a plant-derived polyphenol with known anti-inflammatory properties, mitigates inflammation and gut dysbiosis induced by severe circadian disruption in a rodent model of chronic jet lag Rats were subjected to repeated 12-hour inversions of the light-dark cycle and treated daily with curcumin (40 mg/kg/day) or vehicle delivered orally in almond butter. Circadian disruption significantly increased circulating proinflammatory cytokines and altered gut microbial composition. Curcumin treatment markedly reduced plasma levels of IFN-{gamma}, TNF-, IL-6, and CXCL1, decreased Peyers patch size, and partially restored circadian-regulated activity patterns. Shotgun metagenomic analysis revealed that curcumin shifted the gut microbiome toward a more eubiotic profile, characterized by increased species richness, reduced dominance of inflammatory taxa, decreased relative abundance of Proteobacteria, and increased Firmicutes, with a trend toward enrichment of Actinobacteria. Collectively, these findings demonstrate that curcumin attenuates systemic and intestinal inflammation associated with circadian rhythm disruption, likely through combined suppression of proinflammatory signaling and modulation of the gut microbiome. Despite its limited systemic bioavailability, curcumin exerted robust effects at the gut-immune interface, highlighting the microbiome as a critical therapeutic target for chronobiology-associated inflammatory disorders. These results support curcumin as a potentially promising chronoprotective intervention for conditions characterized by circadian misalignment, including shift work and jet lag.