Emerging roles of the microbiome in cancer

Abstract

Gene-environment interactions underlie cancer susceptibility and progression. Yet, we still have limited knowledge of which environmental factors are important and how they function during tumorigenesis. In this respect, the microbial communities that inhabit our gastrointestinal tract and other body sites have been unappreciated until recently. However, our microbiota are environmental factors that we are exposed to continuously, and human microbiome studies have revealed significant differences in the relative abundance of certain microbes in cancer cases compared with controls. To characterize the function of microbiota in carcinogenesis, mouse models of cancer have been treated with antibiotics. They have also been maintained in a germfree state or have been colonized with specific bacteria in specialized (gnotobiotic) facilities. These studies demonstrate that microbiota can increase or decrease cancer susceptibility and progression by diverse mechanisms such as by modulating inflammation, influencing the genomic stability of host cells and producing metabolites that function as histone deacetylase inhibitors to epigenetically regulate host gene expression. One might consider microbiota as tractable environmental factors because they are highly quantifiable and relatively stable within an individual compared with our exposures to external agents. At the same time, however, diet can modulate the composition of microbial communities within our gut, and this supports the idea that probiotics and prebiotics can be effective chemoprevention strategies. The trajectory of where the current work is headed suggests that microbiota will continue to provide insight into the basic mechanisms of carcinogenesis and that microbiota will also become targets for therapeutic intervention.

Microbiota dysbiosis: a new piece in the understanding of the carcinogenesis puzzle

“…It is known that some pathogens, such as Helicobacter pylori, promote the development of gastric cancer through epithelial damage and inflammation (Petersen & Round, 2014). Other microorganisms, such as viruses, cause cancer through well-described genetic mechanisms, as in the case of human papillomavirus, hepatitis B virus, hepatitis C virus, human herpesvirus 8 and human T-lymphotropic virus 1 (Bultman, 2014;Hassan et al, 2013;Schwabe & Jobin, 2013). However, the role of microorganisms in the initiation and progression of cancer cannot be simply described as a pathogen-related disease (Sheflin et al, 2014).…”

“…The number of microbial cells that colonize the human body is >10 14 , this is 10 times more than the total sum of human somatic and germ cells (Blaser, 2006;Bultman, 2014;Clemente et al, 2012;Petersen & Round, 2014;Plottel & Blaser, 2011). 'Microbiota' is a collective term that refers to the group of microbes including bacteria, fungi, parasites and viruses colonizing the human body (Hassan et al, 2013;Plottel & Blaser, 2011), and the collection of genes they encode is known as our microbiome (Clemente et al, 2012).…”

“…Despite significant progress, the microorganisms that constitute what might be considered a 'normal or healthy microbiota' have not been clearly defined (Clemente et al, 2012;Rajilić-Stojanović , 2013). However, patterns emerge when microbial communities are compared at higher taxonomic levels through molecular profiling (Hooper & Macpherson, 2010) between groups of 'healthy individuals' and cohorts of patients with different pathologies, such as inflammatory bowel disease (IBD), diabetes mellitus, obesity, cardiovascular disease and cancer (Bultman, 2014;Petersen & Round, 2014).…”

T lymphocytes control microbial composition by regulating the abundance of Vibrio in the zebrafish gut

“…[1][2][3][4][5] Dysbiosis may refer to disturbances in the microbial community composition, but can also refer to disturbed interaction between the microbiota and the host. Disturbance of the microbial community due to for example antibiotic use can lead to outgrowth of socalled pathobionts.…”

Crosstalk between the microbiome and cancer cells by quorum sensing peptides

“…In colon cancer patients, an increased population of e.g. Escherichia coli was observed in feces, inducing colitis and colibactin synthesis and thereby promoting inflammation and cancer [12].…”