The microbiome and cancer

Abstract

Microbiota and host form a complex 'super-organism' in which symbiotic relationships confer benefits to the host in many key aspects of life. However, defects in the regulatory circuits of the host that control bacterial sensing and homeostasis, or alterations of the microbiome, through environmental changes (infection, diet or lifestyle), may disturb this symbiotic relationship and promote disease. Increasing evidence indicates a key role for the bacterial microbiota in carcinogenesis. In this Opinion article, we discuss links between the bacterial microbiota and cancer, with a particular focus on immune responses, dysbiosis, genotoxicity, metabolism and strategies to target the microbiome for cancer prevention.

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Figure 1: Mechanisms controlling host–microbiota interactions and associated failures implicated in cancer development.
Figure 2: Mechanisms by which the bacterial microbiome modulates carcinogenesis.
Figure 3: Targeting the bacterial microbiota for therapeutic modulation of carcinogenesis.

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Acknowledgements

R.F.S. was supported by grants from the US National Institutes of Health (NIH) U54CA163111, R01DK076920 and R01AA020211. C.J. acknowledges support from the NIH (RO1DK047700 and RO1DK073338). The authors thank D. Dapito for critical reading of the manuscript.

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Glossary

Adaptive immune responses

As opposed to innate immunity, adaptive immune responses are specific to the type of pathogen that is encountered, thereby providing a tailored (albeit slower) immune response. This acquired response is typically mediated by B and T cells with the subsequent generation of memory cells.

Bacteriocins

Antimicrobial peptides released by bacteria to inhibit growth of similar or closely related microorganisms.

Commensalism

A relationship between two organisms in which one organism benefits, whereas the other does not.

Dysbiosis

A state of microbial composition that is characterized by an unbalanced proportion of bacteria compared with the proportion in a healthy state.

Eubiosis

A state of microbial composition in which population abundances are found in normal proportions and typically associated with healthy individuals.

Facultative anaerobic bacteria

Bacteria that are able to generate energy (ATP) through aerobic respiration (electron transport chain) or through fermentation, depending on the amount of oxygen or fermentable products available.

Germ-free animals

Animals born and raised in a sterile environment; they lack any microorganisms (except endogenous viruses).

Gnotobiotic

Describes an animal with a defined microbial population. These animals are born germ-free and then known microorganisms are introduced; this requires that the animals are housed in isolation, to maintain their defined microbial status.

Horizontal gene transfer

The movement of genetic material from one organism to another, without the need for cell division.

Innate immunity

An immune response that recognizes conserved microbial structures, typically through the action of pattern recognition receptors expressed on host cells.

Metagenome

The collection of genomes from members of a specific microbiota.

Microorganism-associated molecular patterns

(MAMPs). Conserved structural components such as lipopolysaccharide, flagellin and nucleic acids derived from microorganisms that are detected by the host innate immune system.

Muramyl dipeptide

A peptidoglycan derivative that is common to both Gram-positive and Gram-negative bacterial cell walls and that triggers an innate immune response.

Mutualism

A relationship between two organisms, in which both organisms benefit.

Obligate anaerobic bacteria

Bacteria that grow without the need for oxygen.

Parasitism

A relationship in which one organism (pathogen) benefits at the expense of another organism.

Pathobionts

Normally innocuous microorganisms that can behave like pathogens if their abundance increases and/or their environmental conditions change.

Stratum corneum

The outermost layer of the epidermis that forms the protective layer of the skin.

Toll-like receptor

(TLR). A family of evolutionarily conserved receptors that recognize microorganism-associated molecular patterns such as flagellin, lipopolysaccharide or nucleic acids. These receptors have an essential role in innate immune responses.

Tumour tolerance

A state of immune hyporesponsiveness, in which tumour antigens induce T cell tolerance (a process that allows tumour immune evasion).

Virulence factors

Molecules expressed by pathogenic microorganisms that help them to gain a growth advantage in a specific ecosystem. These molecules are often responsible for disease manifestation in the host.

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Schwabe, R., Jobin, C. The microbiome and cancer. Nat Rev Cancer 13, 800–812 (2013). https://doi.org/10.1038/nrc3610

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