Alleviation of excessive intestinal reactive oxygen species induced by circadian rhythm disruption through the Astaxanthin@ <em>Spirulina platensis</em> complex

Circadian rhythm plays a crucial role in maintaining intestinal homeostasis, and conversely, the remodeling of gut microbiota can help regulate circadian rhythm. Although traditional therapeutic strategies involving oral small-molecule drugs can modulate the intestinal health in circadian rhythm disruption (CRD), they are limited by restricted efficacy, dependence, and side effects. Herein, astaxanthin (AXT) and <em>Spirulina platensis </em>(SP) were used to prepare an innovative complex (AXT@SP) by a simple one-step synthesis method to alleviate the excessive intestinal reactive oxygen species (ROS) in CRD. The AXT@SP successfully achieved efficient loading of AXT with the drug loading efficiency of 34.56% and extended the retention time of AXT in the intestine for more than 12 h. As expected, AXT@SP reduced the intestinal ROS generation by 40.7%, restored the circadian oscillation of antioxidant-related indicators, protected the intestinal immune barrier, and reshaped the gut microbiota composition in the intestine of CRD mice. Importantly, AXT@SP restored the circadian peak of γ-aminobutyric acid during the physiological sleeping phase and regulated the phase advance of cortisol at ZT12. Our results suggested that AXT@SP could be exploited as a promising strategy for regulating CRD-related intestinal homeostasis <em>via</em> the gut-brain axis.