The role of the microbiota in inflammation, carcinogenesis, and cancer therapy

Abstract

Commensal microorganisms colonize barrier surfaces of all multicellular organisms, including those of humans. For more than 500 million years, commensal microorganisms and their hosts have coevolved and adapted to each other. As a result, the commensal microbiota affects many immune and nonimmune functions of their hosts, and de facto the two together comprise one metaorganism. The commensal microbiota communicates with the host via biologically active molecules. Recently, it has been reported that microbial imbalance may play a critical role in the development of multiple diseases, such as cancer, autoimmune conditions, and increased susceptibility to infection. In this review, we focus on the role of the commensal microbiota in the development, progression, and immune evasion of cancer, as well as some modulatory effects on the treatment of cancer. In particular, we discuss the mechanisms of microbiota-mediated regulation of innate and adaptive immune responses to tumors, and the consequences on cancer progression and whether tumors subsequently become resistant or susceptible to different anticancer therapeutic regiments. Keywords:Cancer r Cancer Therapy r Cancerogenesis r Inflammation r Microbiota IntroductionEukaryotes evolved from a process of endosymbiosis between different prokaryotic cells (reviewed in [1]). The initial eukaryotes evolved surrounded by microorganisms, such as archaea, bacteria, fungi, and viruses and cross-signaling between eukaryotic cells and commensal microbes mostly regulated nutrition, metabolism, and morphogenesis (reviewed in [2]). In our bodies, commensal microorganisms inhabit all the barrier surfaces with the largest number in the distal ileum and colon and they outnumber the human cells by a ratio of 10:1 [3]. Furthermore, the number of microbial genes is at least 100 times higher than that of human Correspondence: Dr. Giorgio Trinchieri e-mail: trinchig@mail.nih.gov genes, although many of the microbial genes have equivalent functions [4]. Viewed from this perspective, we are symbionts or metaorganisms composed of host and microbial cells, each with their own genes (metagenome) and shared metabolic processes and products (metabolome) [5,6].The cohabitation of early eukaryotes with microorganisms was regulated in part by signaling through Toll/IL-1 receptor domaincontaining proteins that later evolved in higher animal species into the innate Toll-like receptors (TLRs) [7]. The family of cytoplasmic NOD-like receptors developed after multicellularity was established [8]. In higher vertebrates, the innate receptor signaling played an increasingly important role in innate and adaptive immunity against pathogens while still regulating the symbiotic interaction with commensal microorganisms [9]. The interaction of the higher organisms with the commensal microbiota C 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu 18Amiran Dzutsev et al. Eur. J. Immunol. 2015. 45: 17-31 maintains an important role in regulating nutrition, metabolism, homeostasis, development ...

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