Oral Supplementation of Butyrate Reduces Mucositis and Intestinal Permeability Associated with 5‐Fluorouracil Administration

Abstract

Mucositis affects about 40% of patients undergoing chemotherapy. Short chain fatty acids (SCFA), mainly butyrate, are claimed to improve mucosal integrity, reduce intestinal permeability and act as anti-inflammatory agents for the colon mucosa. We evaluated the effects of oral administration of SCFA or butyrate in the 5FU-induced mucositis. Mice received water, SCFA or butyrate during all experiment (10days) and a single dose of 5FU (200mg/kg) 3days before euthanasia. We evaluated inflammatory and histological score by morphometry, and by activity of enzymes specific to neutrophil, eosinophil and macrophage and TLR-4, TNF-alpha and IL6 expressions. Intestinal permeability and tight junction protein ZO-1 expression were evaluated. Mice from the 5FU (5-Fluorouracil) group presented weight loss, ulcerations and inflammatory infiltration of neutrophils and eosinophils, increased expression of IL6 and TNF-alpha and increased intestinal permeability. SCFA minimized intestinal damage, reduced ulcerations without affecting intestinal permeability. Butyrate alone was more efficient at improving those parameters than in SCFA solution and also reduced intestinal permeability. The expression of pro-inflammatory cytokines and ZO-1 tended to be higher in the SCFA supplemented but not in the butyrate supplemented group. We showed the beneficial effects of butyrate on intestinal mucositis and its promising function as an adjuvant in the treatment of diseases not only of the colon, but also of the small intestine.