Topical Probiotic Therapy Reduces Chemotherapy‐Induced Oral Mucositis: Preclinical Evaluation in a Rat Model

ABSTRACT Background Oral mucositis (OM) is a debilitating complication of chemotherapy and radiotherapy, characterized by painful ulcerations and inflammation of the oral mucosa. Current treatments provide limited efficacy and often lack regenerative properties. This study aimed to evaluate the therapeutic potential of topically administered probiotics in a rat model of OM. Methods OM was induced in Sprague–Dawley rats using 5‐fluorouracil (5‐FU) and acetic acid. Rats were randomized into groups receiving topical formulations of Lactobacillus acidophilus , Lactobacillus reuteri , Bacillus clausii , Bacillus coagulans , Lactobacillus plantarum , sucralfate, triamcinolone, and control. Treatments were applied for 5 consecutive days. OM severity was assessed using macroscopic and histopathological scoring, fibrosis grading, and inflammatory markers (TNF‐α, IL‐10, PGE 2 ). Results L. acidophilus and L. reuteri significantly reduced macroscopic and histopathological OM scores compared to controls. L. acidophilus also demonstrated a notable reduction in fibrosis and PGE 2 levels ( p < 0.05), suggesting anti‐inflammatory and antifibrotic activity. B. clausii and B. coagulans showed moderate efficacy, while sucralfate and triamcinolone reduced mucosal inflammation but were less effective in tissue regeneration. No significant changes in IL‐10 were observed across groups. Conclusion Topically applied probiotics, particularly L. acidophilus , exhibit significant therapeutic potential in attenuating chemotherapy‐induced OM by modulating inflammation and promoting mucosal healing. These findings support further exploration of localized probiotic therapies as a novel, non‐systemic approach to manage OM in clinical settings.