ATG5 Overexpression Enhances the Therapeutic Efficacy of Mesenchymal Stem Cells in a Mouse Colitis Model by Augmenting Anti-inflammatory and Antioxidative Mechanisms

• ATG5 overexpression enhances MSC autophagic activity and antioxidant capacity, upregulating HMOX-1, SOD2, and CAT and increasing enzymatic activity. • MSCs-ATG5 promote M2 macrophage polarization and suppress the IL-17/NF-κB inflammatory signaling pathway in a mouse colitis model. • MSCs-ATG5 therapy increases anti-inflammatory metabolite PGD2 and butyrate-producing bacteria, alleviating colitis symptoms. • ATG5-engineered MSCs represent a promising strategy to improve MSC-based therapies for inflammatory bowel disease.