Modeling Gut Barrier Dysfunction and Subsequent Opportunistic Infection by Candida albicans During Chemotherapy-Induced Intestinal Mucositis in Mice.

Abstract

Chemotherapeutic agents exert antineoplastic effects by damaging the DNA of cancer cells, leading to cell death. However, this effect is not specific, and may affect healthy cells and cause several adverse events such as myelosuppression and gastrointestinal mucositis. The term gastrointestinal mucositis refers to lesions in the mucosa, which include the oral cavity, pharynx, larynx, stomach, and intestine. The focus of this chapter will be the chemotherapy-induced intestinal damage, which can lead to weight loss, diarrhea, constipation, and increased predisposition to infections. Despite its severity, there is no treatment available for mucositis, and the pathophysiology of the disease has not been fully elucidated so far. This highlights the relevance of studying the mechanism of the disease and possible intervention strategies in intestinal mucositis. Here, we provide a detailed description of the main methodologies involved in the evaluation of changes induced by chemotherapy in a murine model, namely, 5-Fluorouracil (5-FU)-induced mucositis. These parameters include (i) assessment of body weight, (ii) stool consistency, (iii) fecal occult blood, and (iv) intestinal permeability. In addition, we describe a protocol to model opportunistic infection after chemotherapy, by exposing mice treated with 5-FU to Candida albicans in the drinking water.