Prophylactic and therapeutic supplementation using fructo-oligosaccharide improves the intestinal homeostasis after mucositis induced by 5- fluorouracil

• Main Authors: Paula Lopes Armond Carvalho, Maria Emília Rabelo Andrade, Luísa Martins Trindade, Paola Caroline Lacerda Leocádio, Jacqueline Isaura Alvarez-Leite, Diego Carlos dos Reis, Geovanni Dantas Cassali, Éricka Lorenna de Sales Souza e Melo, Flaviano dos Santos Martins, Simone Odília Antunes Fernandes, Maria do Carmo Gouveia Peluzio, Simone de Vasconcelos Generoso, Valbert Nascimento Cardoso
• Format: Article
• Language: English
• Published: Elsevier 2021-01-01
• Series: Biomedicine & Pharmacotherapy
• Subjects: Mucositis; Intestinal damage; Tight junction; Short-chain fatty acids; 5-Fluorouracil; Fructo-oligosaccharide
• Online Access: http://www.sciencedirect.com/science/article/pii/S075333222031204X

The beneficial effects of prebiotic, such as fructo-oligosaccharides (FOS), in intestinal inflammation have been demonstrated in several studies. Herein, we evaluate whether joint treatment with FOS, both before and during mucositis, had additional beneficial effects and investigated the mechanisms underlying in the action of FOS on the intestinal barrier. BALB/c mice were randomly divided into five groups: CTR (without mucositis + saline solution), FOS (without mucositis + 6 % FOS), MUC (mucositis + saline solution), PT (mucositis + 6 % FOS supplementation before disease induction), and TT (mucositis + 6 % FOS supplementation before and during disease induction). Mucositis was induced by intraperitoneal injection (300 mg/kg) of 5-fluorouracil (5-FU). After 72 h, the animals were euthanized and intestinal permeability (IP), tight junction, bacterial translocation (BT), histology and morphometry, and immunoglobulin A secretory (sIgA), inflammatory infiltrate, and production of short-chain fatty acids (acetate, butyrate and propionate) were evaluated. The MUC group showed an increase in the IP, BT, and inflammatory infiltrate but a decrease in the tight junction expression and butyrate and propionate levels (P < 0.05). In the PT and TT groups, FOS supplementation maintained the IP, tight junction expression, and propionate concentration within physiologic levels, increased butyrate levels, and reduced BT and inflammatory infiltrate (P < 0.05). Total treatment with FOS (TT group) was more effective in maintaining histological score, morphometric parameters, and sIgA production. Thus, total treatment (prophylactic and therapeutic supplementation) with FOS was more effective than pretreatment alone, in reducing 5-FU-induced damage to the intestinal barrier.