Yi-Fang Zhang,1 Ting Ting Shi,1 Yi-Ling Lin,2 Yu-Ting Zhu,3 Shu Lin,4,5 Tai-Yong Fang1 

1Department of Gastroenterology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, People’s Republic of China; 2Department of Gastroenterology, Anxi Maternal and Child Health Hospital, Quanzhou, Fujian, People’s Republic of China; 3School of Medicine and School of Biomedical Sciences, Huaqiao University, Quanzhou, 362000, People’s Republic of China; 4Centre of Neurological and Metabolic Research, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, People’s Republic of China; 5Group of Neuroendocrinology, Garvan Institute of Medical Research, Sydney, NSW, Australia

Correspondence: Shu Lin, Centre of Neurological and Metabolic Research, The Second Affiliated Hospital of Fujian Medical University, No. 34 North Zhongshan Road, Quanzhou, Fujian, 362000, People’s Republic of China, Tel +86 15659068071, Email shulin1956@126.com Tai-Yong Fang, Department of Gastroenterology, The Second Affiliated Hospital of Fujian Medical University, No. 34 North Zhongshan Road, Quanzhou, Fujian, 362000, People’s Republic of China, Tel +86 13805992641, Email fangtaiyong122@126.com

Abstract: Inflammatory bowel disease (IBD), encompassing two subtypes, ulcerative colitis, and Crohn’s disease, is a chronic, non-specific gastrointestinal disorder with a complex etiology stemming from various factors. The incidence of IBD has been steadily rising in the past few years, causing great physical and mental strain on patients. Traditional IBD therapeutic drugs include anti-inflammatory drugs, immunosuppressants, and biologics; however, they may have serious adverse effects. This has fueled active clinical research exploring new targets for IBD treatment, focusing on the unique metabolic pathways and functions of macrophages. Macrophage immune metabolism plays a crucial role in IBD; however, the mechanism is unclear. This review discussed the role and potential mechanisms of macrophage metabolic reprogramming in IBD and the link between macrophages and ferroptosis. While these findings from preclinical models suggest novel therapeutic avenues for IBD, such as targeting macrophage metabolic reprogramming and hypothetical approaches like ferroptosis modulation, their clinical applicability remains speculative; rigorous disease-specific validation is imperative.

Keywords: macrophage, metabolic reprogramming, inflammatory bowel diseases, pathogenesis, therapy