The Microbiome as a Component of the Tumor Microenvironment

Abstract

Microbes, which live in the human body, affect a large set of pathophysiological processes. Changes in the composition and proportion of the microbiome are associated with metabolic diseases (Fulbright et al., PLoS Pathog 13:e1006480, 2017; Maruvada et al., Cell Host Microbe 22:589–599, 2017), psychiatric disorders (Macfabe, Glob Adv Health Med 2:52–66, 2013; Kundu et al., Cell 171:1481–1493, 2017), and neoplastic diseases (Plottel and Blaser, Cell Host Microbe 10:324–335, 2011; Schwabe and Jobin, Nat Rev Cancer 13:800–812, 2013; Zitvogel et al., Cell 165:276–287, 2016). However, the number of directly tumorigenic bacteria is extremely low. Microbial dysbiosis is connected to cancers of the urinary tract (Yu, Arch Med Sci 11:385–394, 2015), cervix (Chase, Gynecol Oncol 138:190–200, 2015), skin (Yu et al., J Drugs Dermatol 14:461–465, 2015), airways (Gui et al., Genet Mol Res 14:5642–5651, 2015), colon (Garrett, Science 348:80–86, 2015), lymphomas (Yamamoto and Schiestl, Int J Environ Res Public Health 11:9038–9049, 2014; Yamamoto and Schiestl, Cancer J 20:190–194, 2014), prostate (Yu, Arch Med Sci 11:385–394, 2015), and breast (Flores et al., J Transl Med 10:253, 2012; Fuhrman et al., J Clin Endocrinol Metab 99:4632–4640, 2014; Xuan et al., PLoS One 9:e83744, 2014; Goedert et al., J Natl Cancer Inst 107:djv147, 2015; Chan et al., Sci Rep 6:28061, 2016; Hieken et al., Sci Rep 6:30751, 2016; Urbaniak et al., Appl Environ Microbiol 82:5039–5048, 2016; Goedert et al., Br J Cancer 118:471–479, 2018). Microbial dysbiosis can influence organs in direct contact with the microbiome and organs that are located at distant sites of the body. The altered microbiota can lead to a disruption of the mucosal barrier (Plottel and Blaser, Cell Host Microbe 10:324–335, 2011), promote or inhibit tumorigenesis through the modification of immune responses (Kawai and Akira, Int Immunol 21:317–337, 2009; Dapito et al., Cancer Cell 21:504–516, 2012) and microbiome-derived metabolites, such as estrogens (Flores et al., J Transl Med 10:253, 2012; Fuhrman et al., J Clin Endocrinol Metab 99:4632–4640, 2014), secondary bile acids (Rowland, Role of the gut flora in toxicity and cancer, Academic Press, London, p x, 517 p., 1988; Yoshimoto et al., Nature 499:97–101, 2013; Xie et al., Int J Cancer 139:1764–1775, 2016; Shellman et al., Clin Otolaryngol 42:969–973, 2017; Luu et al., Cell Oncol (Dordr) 41:13–24, 2018; Miko et al., Biochim Biophys Acta Bioenerg 1859:958–974, 2018), short-chain fatty acids (Bindels et al., Br J Cancer 107:1337–1344, 2012), lipopolysaccharides (Dapito et al., Cancer Cell 21:504–516, 2012), and genotoxins (Fulbright et al., PLoS Pathog 13:e1006480, 2017). Thus, altered gut microbiota may change the efficacy of chemotherapy and radiation therapy (McCarron et al., Br J Biomed Sci 69:14–17, 2012; Viaud et al., Science 342:971–976, 2013; Montassier et al., Aliment Pharmacol Ther 42:515–528, 2015; Buchta Rosean et al., Adv Cancer Res 143:255–294, 2019). Taken together, microbial dysbiosis has intricate connections with neoplastic diseases; hereby, we aim to highlight the major contact routes.