5-Fluorouracil-induced intestinal mucositis: Pathogenesis and potential therapeutic interventions

Intestinal mucositis is one of the most common toxicities of 5-fluorouracil (5-FU)-based chemotherapy, occurring in up to 80% of treated patients. Clinically, it presents as abdominal pain, watery or bloody diarrhea, malabsorption and body-weight loss, often forcing chemotherapy dose reduction or discontinuation, thereby aggravating the psychological burden of patients, prolonging hospital stay and potentially increasing mortality. Histologically, 5-FU-induced intestinal mucositis (FIM) is characterized by villus atrophy, crypt apoptosis, disruption of epithelial barrier and pronounced inflammatory infiltration. In this review, we delineate the mechanisms of FIM, a multi-stage pathogenesis that integrates direct epithelial cell apoptosis, oxidative stress, inflammation signal cascades, intestinal barrier disruption, dysbiosis, as well as more recently recognized factors such as impaired intestinal neuroregulation and intestinal senescence. Additionally, we summarize the potential pharmacological interventions, aiming to offer a reference for future basic and clinical research on FIM.