Gastrointestinal digestion unlocks the anti-inflammatory and gut-protective potential of Chlamydomonas reinhardtii protein in colitis: Insights into microbial modulation.

Chlamydomonas reinhardtii (C. reinhardtii) is an emergent edible microalga with high nutritional value. This study investigated how gastrointestinal digestion influences the anti-inflammatory and intestinal-protective properties of its protein (CRP) against colitis. In vitro digestion of CRP yielded a hydrolysate (CRPH) with enhanced antioxidant capacities and potent anti-inflammatory effects in LPS-stimulated RAW 264.7 macrophages, reducing pro-inflammatory cytokines and NO levels. In vivo, oral CRP supplementation in dextran sulfate sodium (DSS)-induced colitis mice significantly alleviated disease severity, restored intestinal barrier integrity by up-regulating tight junction proteins, and bolstered colonic antioxidant defenses. Furthermore, CRP modulated the gut microbiota, enriching homeostasis-associated taxa while suppressing inflammation-related genera. These descriptive findings highlight digested C. reinhardtii protein as a promising functional food ingredient for managing colitis, providing a solid basis for future structural and mechanistic investigations.