Succinate’s Dual Roles in Inflammatory Bowel Disease: A Narrative Review of Microbiota-Metabolism-Immune Crosstalk and Therapeutic Implications

Meihua Zhao,1 Chuan Zhou,1 Dandan Wang,1 Qiong Wu,2 Baisui Feng1 1Department of Gastroenterology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Pathology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of ChinaCorrespondence: Baisui Feng, Department of Gastroenterology, The Second Affiliated Hospital of Zhengzhou University, No. 2 Courtyard, Jingba Road, Zhengzhou, Henan, People’s Republic of China, Email [email protected]: Inflammatory bowel disease (IBD) is a chronic intestinal condition characterized by microbial dysbiosis, metabolic alterations, and immune dysregulation. Succinate, a key tricarboxylic acid (TCA) cycle intermediate and microbiota-derived metabolite, has emerged as a central regulator within the host microbiota-metabolism-immune axis in IBD. This narrative review delineates succinate metabolism and its dual signaling roles, operating both intracellularly and through extracellular receptors. We synthesize evidence on its context-dependent immunomodulatory functions, which can paradoxically drive both pro- and anti-inflammatory responses, and elucidate the specific factors that dictate these outcomes. Finally, we critically evaluate the translational potential of targeting the succinate pathway, outlining promising avenues for future research in IBD diagnosis and treatment. Keywords: succinate, inflammatory bowel disease, immune regulation, microbiota-metabolism-immune axis, precision medicine