Impact of the Microbiota on Bacterial Infections during Cancer Treatment

Bacterial infections occur frequently in the oncologic setting, and antibiotic treatment is increasingly problematic. Therefore, alternative prognostic and treatment strategies for infection are necessary. Recent characterization of the microorganisms (bacteria, fungi, and viruses) inhabiting the human body has revealed the microbiome as an important contributor to host physiology and pathology. The importance of host immune system–microbiota interface has been highlighted by studies demonstrating that microbiota dysbiosis is associated with immune dysfunction, mucosal barrier disruption, and impaired colonization resistance against translocating microbes. Novel microbiome-based therapeutic strategies, using fecal microbiome transplant, probiotics, or prebiotics, are being studied in order to mitigate infections as well as improve cancer outcomes through immunomodulation. Patients being treated for cancer are at high risk for infectious complications, generally due to colonizing organisms that gain access to sterile sites via disrupted epithelial barriers. There is an emerging understanding that the ability of bacterial pathogens, including multidrug-resistant organisms, to colonize and subsequently infect humans is largely dependent on protective bacterial species present in the microbiome. Thus, herein we review recent studies demonstrating strong correlations between the microbiome of the oncology patient and infections occurring during chemotherapy. An increased knowledge of the interplay between potential pathogens, protective commensals, and the host immune system may facilitate the development of novel biomarkers or therapeutics that could help ameliorate the toll that infections take during the treatment of cancer. Patients being treated for cancer are at high risk for infectious complications, generally due to colonizing organisms that gain access to sterile sites via disrupted epithelial barriers. There is an emerging understanding that the ability of bacterial pathogens, including multidrug-resistant organisms, to colonize and subsequently infect humans is largely dependent on protective bacterial species present in the microbiome. Thus, herein we review recent studies demonstrating strong correlations between the microbiome of the oncology patient and infections occurring during chemotherapy. An increased knowledge of the interplay between potential pathogens, protective commensals, and the host immune system may facilitate the development of novel biomarkers or therapeutics that could help ameliorate the toll that infections take during the treatment of cancer. the number and distribution of taxa present in a single population or specimen. the taxonomic diversity differences between two populations or samples. bactericidal peptides produced by microorganisms or host cells. immunomodulatory members of the microbiota. toxins secreted by bacteria to kill other bacteria. administration of live bacteria, (e.g., the probiotic which refers to the specific organism or cocktail of organisms) in order to restore health or cure disease. a short-chain fatty acid important as an energy source for colonic epithelium. direct or indirect protection against pathogen or pathobiont colonization exerted by commensal bacteria. a change from steady-state composition within a microbial ecosystem. restoration of the colonic microflora by introducing healthy bacterial flora through infusion of stool obtained from a healthy donor. cancers that affect the blood and lymph system. the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood. the processes by which the lysine residues within the N-terminal tail of the histone core of a nucleosome are acetylated as part of gene regulation. a particular genus contributing >30% of 16S rRNA reads retrieved from a gastrointestinal microbiome sample. the collection of microorganisms and microbial genomes that contribute to the metagenome of a human. the collection of microorganisms that live on and within humans. heavily glycosylated proteins produced by epithelial tissues which comprise mucus and other secretions. damage that occurs to the mucosal lining of the gastrointestinal tract typically during chemotherapy or radiation. killing of cells in the bone marrow, including both normal blood-forming cells and cancer cells, during high-dose chemotherapy. abnormally low level of neutrophils in the blood. intracellular sensors, found in lymphocytes, macrophages, dendritic cells, and other cells, that regulate inflammatory and apoptotic responses. any potentially pathological organism which, under normal circumstances, lives as a symbiont. substances that induce the growth or activity of microorganisms that contribute to host health. CD4+ T cells which produce IL-10, express FoxP3, and are crucial to maintaining tolerance to self-antigens. in mice, nonpathogenic members of the gut microbiota that preferentially attach to the intestinal epithelium and potently induce immune responses. fatty acids, produced by bacteria through fermentation of fiber/starches, which act as signaling molecules. a subset of proinflammatory CD4+ T cells, which produce Il-17 and RORγt, specializing in maintaining mucosal barriers and pathogen clearance. receptors that recognize structurally conserved structures from microbes and activate innate immune responses. producing immunologic tolerance.