Lactobacillus casei Variety rhamnosus Probiotic Preventively Attenuates 5-Fluorouracil/Oxaliplatin-Induced Intestinal Injury in a Syngeneic Colorectal Cancer Model

SUMMARY

Gastrointestinal toxicity due to chemotherapeutic drugs is a major cause of morbidity and mortality in cancer patients. Mucositis and diarrhea are the most significant enterotoxicities. Lesions associated with mucositis result in pain, decreased quality of life, increased length of hospitalization, higher risk of infection, and modification of anti-neoplastic treatment regimens (Sonis et al., 2004; Sharma et al., 2005; Lee et al., 2014). The pathophysiology of chemotherapy-induced mucositis remains unclear and involves a complex and dynamic array of biological events (Logan et al., 2007; Lee et al., 2014). Some studies have suggested a five-stage process, including an initiation phase, a message generation phase, a signaling and amplification phase, an ulceration phase, and a spontaneous healing phase (Sonis et al., 2004; Logan et al., 2007). The pathophysiology might include decreased villi length and disruption of crypt cell homeostasis, and several pathogenic elements are involved, including direct toxicity, a change in the balance of bowel microbial flora, oxidative stress, apoptosis, hypoproliferation, and abnormal inflammation. Recent studies have revealed that chemotherapeutics affect the intestinal microbial composition (Stringer et al., 2009a,b) and fecal microbiota (Touchefeu et al., 2014). However, no well-established or up-to-date therapeutic strategy is available to manage chemotherapy-induced intestinal mucositis (Sharma et al., 2005). Thus, the development of an effective intervention against chemotherapy-related mucositis is urgently needed for oncological supportive care.

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