Understanding chemotherapy-induced intestinal mucositis and strategies to improve gut resilience

Abstract

Intestinal mucositis remains one of the most debilitating side effects related to chemotherapy. The onset and persistence of mucositis is an intricate physiological process involving cross-communication between the specific chemotherapeutic drug, the immune system, and gut microbes that results in a loss of mucosal integrity leading to gut-barrier dysfunction. Intestinal mucositis has a severe impact on a patient's quality of life and negatively influences the outcome of treatment. Most importantly, intestinal mucositis is a major contributor to the decreased survival rates and early onset of death associated with certain chemotherapy treatments. Understanding the pathophysiology and symptomology of intestinal mucositis is important in reducing the negative consequences of this condition. Prophylaxis, early diagnosis, and proper symptom management are essential to improved survival outcomes in patients with cancer. This review focuses on the pathobiology of intestinal mucositis that accompanies chemotherapy treatments. In addition, we will discuss the therapeutic potential of select strategies that have shown promise in mitigating chemotherapies' off-target effects without hampering their anticancer efficacy.NEW & NOTEWORTHY Intestinal mucositis, or damage to the intestinal mucosa, is a common side effect of chemotherapy. In this review, we describe the pathobiology of intestinal mucositis that is associated with chemotherapy treatments. In addition, we discuss the efficacy of several potential therapeutic strategies that have shown some potential in alleviating chemotherapies' off-target effects.

Keywords: chemotherapy; gut resilience; inflammation; intestinal mucositis; therapeutic strategies.

Graphical abstract

Figure 1.

The pathobiology of mucositis. This model illustrates significant events in the onset and progression of chemotherapy-induced intestinal mucositis. The presented timeline was developed based on analysis of multiple investigations in preclinical and clinical models of intestinal mucositis. Onset of specific biomolecular consequences and immune cell responses may vary based on drug dose and frequency. Simply, at higher dose or greater frequency, chemotherapy is more likely to accelerate the histopathological, biomolecular, and immune cell consequences presented in this figure. Image adapted from Sonis (22). COX2, cyclooxygenase-2; IL1β, interleukin 1β; IL6, interleukin 6; NF-κB, nuclear factor κ-B; ROS, reactive oxygen species; TNFα, tumor necrosis factor α.