Tea plant-inspired nanoassembled supraparticles alleviate colitis and associated mental disorders via microbiota-gut-brain interactions

<b>Background:</b> Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract that significantly impacts patient health and quality of life. (-)-Epigallocatechin-3-gallate (EGCG), a potent plant polyphenol from green tea, exhibits superior anti-inflammatory and antioxidative properties; however, its therapeutic potential is hindered by poor stability and bioavailability. <b>Methods and results:</b> Inspired by the tea plant (<i>Camellia sinensis</i>), we developed EGCG-loaded tea supraparticles (TSPs) as an oral dietary supplement, utilizing tea proteins, an eco-friendly byproduct with inherent antioxidative potential, to deliver EGCG. TSPs greatly improved EGCG's stability during gastrointestinal transport, preserving its antioxidant properties and its ability to modulate the immune microenvironment. In a dextran sulfate sodium salt-induced colitis mouse model, TSPs treatment reduced the disease activity index by more than 70% and showed a 1.53-fold improvement in efficacy than EGCG alone. Enhanced colonic barrier integrity and anti-inflammatory effects were observed by oral administration of TSPs. Furthermore, TSPs modulated gut microbiota, promoting microbial diversity and homeostasis thereby alleviating systemic inflammation. This reduction in inflammation contributed to improved blood-brain barrier integrity, potentially mitigating anxiety and depressive-like behaviors associated with colitis. <b>Conclusion:</b> These findings highlight the potential of TSPs as a sustainable nanotechnology-based strategy for enhancing the efficacy of EGCG and effectively addressing IBD and its associated complications.