Lyophilized Symbiotic Mitigates Mucositis Induced by 5-Fluorouracil
Bruna Savassi, Bárbara Fernandes Cordeiro, Sara H. Silva, Emiliano Rosa Oliveira, Giovanna Angeli Belo, Alessandra Figueiroa, Maria Izabel Alves Queiroz, Ana Maria Caetano Faria, Juliana de Jesus Monteiro Alves, Tales Fernando da Silva, Gabriela Munis Campos, Erick A. Esmerino, Ramon S. Rocha, Mônica Q. Freitas, Márcia C. Silva, Adriano G. Cruz, Kátia Duarte Vital, Simone Odília Antunes Fernandes, Valbert Nascimento Cardoso, Leonardo Borges Acúrcio, Gwénaël Jan, Yves Le Loir, Alfonso Gala-García, Fillipe Luiz Rosa Do Carmo, Vasco Azevedo
Abstract
Mucositis is an adverse effect of cancer chemotherapies using 5-Fluorouracil (5-FU). It is characterized by mucosal inflammation, pain, diarrhea, and weight loss. Some studies reported promising healing effects of probiotic strains, when associated with prebiotics, as adjuvant treatment of mucositis. We developed a lyophilized symbiotic product, containing skimmed milk, supplemented with whey protein isolate (WPI) and with fructooligosaccharides (FOS), and fermented by Lactobacillus casei BL23, Lactiplantibacillus plantarum B7, and Lacticaseibacillus rhamnosus B1. In a mice 5-FU mucositis model, this symbiotic lyophilized formulation was able to reduce weight loss and intestinal permeability. This last was determined in vivo by quantifying blood radioactivity after oral administration of 99mTc-DTPA. Finally, histological damages caused by 5-FU-induced mucositis were monitored. Consumption of the symbiotic formulation caused a reduced score of inflammation in the duodenum, ileum, and colon. In addition, it decreased levels of pro-inflammatory cytokines IL-1β, IL-6, IL-17, and TNF-α in the mice ileum. The symbiotic product developed in this work thus represents a promising adjuvant treatment of mucositis.