4 GUT MICROBIOTA-MEDIATED DRUG GASTROINTESTINAL TOXICITY
The gastrointestinal reaction is a commonly observed drug side effect especially for chemotherapeutical agents and is characterized by nausea, vomiting, diarrhea, and constipation (Ervin et al., 2020). Studies have revealed the pivotal role of gut microbiota in therapeutic and toxic outcomes of cancer therapy (Roy and Trinchieri, 2017; Gopalakrishnan et al., 2018; Gori et al., 2019) and gut microbiome can even be used as a tool to anticipate individual gastrointestinal toxicity (Wardill and Tissing, 2017). It is believed that reciprocal interactions between gut microbiota and innate immunity contributes to chemotherapy-induced gastrointestinal toxicity (Secombe et al., 2019) and modulation of gut microbiota by probiotics has been proven to attenuate gastrointestinal toxicity of cancer therapy in human trials (Ciorba et al., 2015). Chemotherapy-induced gastrointestinal side effects negatively influence nutritional status and life quality of patients but most importantly they intervene adherence to chemotherapy regiment, causing much difficulty in the process of cancer therapy and prognosis (Ervin et al., 2020) and therefore coping with this problem is of utmost importance in cancer therapy. Gut microbiota hitherto has been correlated with methotrexate, irinotecan, 5-fluorouracil, and mycophenolate mofetil-induced gastrointestinal toxicity (Fig.4).