Prebiotics: A Potential Treatment Strategy for the Chemotherapy-damaged Gut?

Abstract

Mucositis, characterized by ulcerative lesions along the alimentary tract, is a common consequence of many chemotherapy regimens. Chemotherapy negatively disrupts the intestinal microbiota, resulting in increased numbers of potentially pathogenic bacteria, such as Clostridia and Enterobacteriaceae, and decreased numbers of "beneficial" bacteria, such as Lactobacilli and Bifidobacteria. Agents capable of restoring homeostasis in the bowel microbiota could therefore be applicable to mucositis. Prebiotics are indigestible compounds, commonly oligosaccharides, which seek to reverse chemotherapy-induced intestinal dysbiosis through selective colonization of the intestinal microbiota by probiotic bacteria. In addition, evidence is emerging that certain prebiotics contribute to nutrient digestibility and absorption, modulate intestinal barrier function through effects on mucin expression, and also modify mucosal immune responses, possibly via inflammasome-mediated processes. This review examines the known mechanisms of prebiotic action and explores their potential to reduce the severity of chemotherapy-induced mucositis in the intestine. MUCOSITISThe treatment of cancer by chemotherapy, sometimes in combination with radiotherapy, is associated with an array of acute side-effects, including alopecia, neutropenia and nausea (Logan et al., 2007). Furthermore, these treatments can also induce inflammation and deterioration of the mucosal membranes of the alimentary tract, a condition referred to as mucositis. Mucositis can occur throughout the entire gastrointestinal tract (Gibson et al., 2005); however, it most commonly affects the mucosa of the mouth (oral mucositis) and small intestine (gastrointestinal mucositis), with symptoms including pain, vomiting, bloating, and diarrhoea. Severe cases are often associated with secondary complications such as malnutrition and septicaemia, resulting in poor patient outcomes. Indeed, the pathobiology of mucositis is influenced by the nature of the causative agent (Logan et al., 2009), with temporal variations in pathogenesis, in addition to the location and severity of damage (Logan et al., 2009). Consequently, the multi-factorial nature of mucositis makes it a difficult condition to understand, and subsequently treat.Despite mucositis being one of the most common side-effects of cancer treatment (Choi et al., 2007) its incidence and severity is highly variable, and is dependent on the treatment regimen and individual variation in terms of tolerability . Approximately 40% of all patients undergoing chemotherapy develop mucositis (Gibson et al., 2002; with this number rising to between 60% and 100% in patients receiving high-dose chemotherapy regimens for conditions such as the haematological malignancies (Gibson et al., 2002;. To date, effective treatments for intestinal mucositis have been elusive. Potential treatment options are limited by the requirement for treatments to protect the mucosa and promote the repair process, without compromising cytotoxic effects on the ...

Current Challenges in Cancer Immunotherapy: Multimodal Approaches to Improve Efficacy and Patient Response Rates

“…In order to be classified as a prebiotic, a compound must be indigestible and not absorbed in the small intestine. However, it must also have the capacity to rebalance the gut microbiota to that of a healthier composition in addition to being selectively fermented by beneficial bacteria in the colon [36]. The latter leads to the production of short-chain fatty acids (SCFAs) in the colon [37].…”

Altered gut microbiota associated with symptom severity in schizophrenia

“…Changes in the gut microbiota and its metabolites may cause neuronal damage, apoptosis and abnormal brain development, leading to SZ ( Yuan et al, 2019 ). An increase in intestinal mucosal permeability induced by gut microbiota dysbiosis leads to alterations in intestinal membrane proteins zonulin and mucin and in metabolites indolepropionic acid (IPA), lipopolysaccharides (LPS) and SCFA ( Wang, Geier & Howarth, 2016 ). The metabolite IPA of gut microbiota maintains gut mucosal barrier integrity and Homeostasis of monocytes and T cells ( Dodd et al, 2017 ).…”

A review of complementary therapies for chemotherapy induced gastrointestinal mucositis

“…Therefore, maintaining a healthy microbiota and mucin layer during chemotherapy treatment could minimise the complications associated with GIM. In this context, probiotic microorganisms represent a promising therapeutic option in treatment of GIM (69,70). Probiotics are defined as living microorganisms which when administered in adequate amounts, exert desirable health benefits on the host (71).…”