The Role of Intestinal Microbiota in the Development and Severity of Chemotherapy-Induced Mucositis
Top Cited Papers
Open Access
- 27 May 2010
- journal article
- review article
- Published by Public Library of Science (PLoS) in PLoS Pathogens
- Vol. 6 (5), e1000879
- https://doi.org/10.1371/journal.ppat.1000879
Abstract
Mucositis, also referred to as mucosal barrier injury, is one of the most debilitating side effects of radiotherapy and chemotherapy treatment. Clinically, mucositis is associated with pain, bacteremia, and malnutrition. Furthermore, mucositis is a frequent reason to postpone chemotherapy treatment, ultimately leading towards a higher mortality in cancer patients. According to the model introduced by Sonis, both inflammation and apoptosis of the mucosal barrier result in its discontinuity, thereby promoting bacterial translocation. According to this five-phase model, the intestinal microbiota plays no role in the pathophysiology of mucositis. However, research has implicated a prominent role for the commensal intestinal microbiota in the development of several inflammatory diseases like inflammatory bowel disease, pouchitis, and radiotherapy-induced diarrhea. Furthermore, chemotherapeutics have a detrimental effect on the intestinal microbial composition (strongly decreasing the numbers of anaerobic bacteria), coinciding in time with the development of chemotherapy-induced mucositis. We hypothesize that the commensal intestinal microbiota might play a pivotal role in chemotherapy-induced mucositis. In this review, we propose and discuss five pathways in the development of mucositis that are potentially influenced by the commensal intestinal microbiota: 1) the inflammatory process and oxidative stress, 2) intestinal permeability, 3) the composition of the mucus layer, 4) the resistance to harmful stimuli and epithelial repair mechanisms, and 5) the activation and release of immune effector molecules. Via these pathways, the commensal intestinal microbiota might influence all phases in the Sonis model of the pathogenesis of mucositis. Further research is needed to show the clinical relevance of restoring dysbiosis, thereby possibly decreasing the degree of intestinal mucositis.Keywords
This publication has 99 references indexed in Scilit:
- Irinotecan‐induced mucositis manifesting as diarrhoea corresponds with an amended intestinal flora and mucin profileInternational Journal of Experimental Pathology, 2009
- Function of Nod‐like receptors in microbial recognition and host defenseImmunological Reviews, 2008
- Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patientsProceedings of the National Academy of Sciences of the United States of America, 2008
- The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteriaProceedings of the National Academy of Sciences of the United States of America, 2008
- Microbe sampling by mucosal dendritic cells is a discrete, MyD88-independent stepin ΔinvG S. Typhimurium colitisThe Journal of Experimental Medicine, 2008
- Recognition of microorganisms and activation of the immune responseNature, 2007
- Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseasesProceedings of the National Academy of Sciences of the United States of America, 2007
- Soluble Proteins Produced by Probiotic Bacteria Regulate Intestinal Epithelial Cell Survival and GrowthGastroenterology, 2007
- An obesity-associated gut microbiome with increased capacity for energy harvestNature, 2006
- Functional modulation of human intestinal epithelial cell responses by Bifidobacterium infantis and Lactobacillus salivariusImmunology, 2006