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Anticancer effects of the microbiome and its products

Key Points

  • The evolution of cancer has been linked to shifts in the microbiome.

  • It will be indispensable to identify individual strains and clones (rather than phyla and genera) that have optimal anticancer effects. For this, culturomics will be superior to deep-sequencing approaches.

  • Therapeutic manipulation of the cancer-associated microbiome may be obtained by faecal microbiota transplantation, antibiotic treatment, prebiotics that favour the expansion of useful bacteria, dietary interventions or drugs that alter the composition of the gut flora.

  • In preclinical models, defined strains of live microbial agents may be used to stimulate immunosurveillance against cancers, either alone or in combination with cancer therapeutics.

  • Bacterial products that have potential antineoplastic or immunostimulatory properties include bacterial toxins, microbial ligands of pattern recognition receptors, as well as bacterial metabolites, including butyrate, polyamines and pyridoxine.

  • Drugs that modify bacterial metabolism are being developed with the scope of inhibiting the production of carcinogenic products.

Abstract

The human gut microbiome modulates many host processes, including metabolism, inflammation, and immune and cellular responses. It is becoming increasingly apparent that the microbiome can also influence the development of cancer. In preclinical models, the host response to cancer treatment has been improved by modulating the gut microbiome; this is known to have an altered composition in many diseases, including cancer. In addition, cancer treatment with microbial agents or their products has the potential to shrink tumours. However, the microbiome could also negatively influence cancer prognosis through the production of potentially oncogenic toxins and metabolites by bacteria. Thus, future antineoplastic treatments could combine the modulation of the microbiome and its products with immunotherapeutics and more conventional approaches that directly target malignant cells.

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Figure 1: Interventions on the microbiota in cancer.
Figure 2: Potential immune mechanisms that explain the anticancer effects of probiotics.
Figure 3: Anticancer effects of bacterial products.

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Acknowledgements

L.Z. and G.K. are supported by the Institut National Du Cancer (INCA), the Ligue contre le Cancer (équipe labelisée); Agence Nationale de la Recherche (ANR) – Projets blancs; ANR under the frame of E-Rare-2, the ERA-Net for Research on Rare Diseases; Association pour la recherche sur le cancer (ARC); Cancéropôle Ile-de-France; Institut National du Cancer (INCa); Institut Universitaire de France; Fondation pour la Recherche Médicale (FRM); the European Commission (ArtForce); the European Research Council (ERC); the LabEx Immuno-Oncology; the SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); the SIRIC Cancer Research and Personalized Medicine (CARPEM); the Paris Alliance of Cancer Research Institutes (PACRI); and the PIA2 TORINO-LUMIERE. L.Z. is also supported by the Swiss Institute for Experimental Cancer Research (ISREC), by the Swiss Bridge Foundation, and by IMMUNTRAIN-H2020. G.K. is also supported by the LeDucq Foundation.

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Correspondence to Laurence Zitvogel or Guido Kroemer.

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L.Z. and G.K. receive research support by Lytix Ltd and are co-founders of the biotechnological company EverImmune.

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Glossary

Microbiome

The collective genomes that can be found within a single microbial ecosystem.

Microbiota

The community of microorganisms that exist within a single ecosystem.

Metabolic syndrome

A syndrome characterized by central obesity, dyslipidaemia, increased blood pressure and high blood-sugar levels, increased risk of type 2 diabetes and cardiovascular disease.

Immunosurveillance

A term that is used to describe the processes by which cells of the immune system hunt and target pathogens, such as bacteria and viruses, or pre-cancerous and cancerous host cells.

Pattern recognition receptors

(PRRs). Innate immune components expressed by various cell types to sense infection or tissue damage.

Toll-like receptors

Pattern recognition receptors that mostly recognize bacterial structures.

Immune-checkpoint blockade

A pharmacological intervention whereby monoclonal antibodies neutralize major inhibitory receptors (such as cytotoxic T lymphocyte protein 4 (CTLA4) and programmed cell death 1 (PD1)) expressed by activated lymphocytes to alleviate immune suppression and restore lymphocyte effector functions.

Faecal microbiota transplantation

The engraftment of microbiota from a healthy donor into a recipient, which results in the restoration of the normal gut microbial ecosystem.

Graft-versus-host disease

An immune attack of transplanted lymphocytes against host cells, which causes systemic disease following the transfusion of cells from a donor that has distinct histocompatibility antigens.

Probiotic

A live microorganism that can confer a health benefit to the host.

Prebiotic

A non-digestible food ingredient that stimulates the growth and activity of bacteria in the digestive system.

Autophagy

A mechanism of lysosomal degradation that enables the degradation and recycling of cytoplasmic material sequestered in autophagosomes.

Sarcopenia

The degenerative loss of skeletal muscle mass, quality and strength associated with ageing, frailty syndrome and/or cachexia.

Thymus atrophy

An age-dependent reduction in thymic mass that may be accelerated in pathological conditions.

TH17 cell

(T helper 17 cell). A CD4+ T helper cell induced by the coordinated action of transforming growth factor-β (TGFβ) and interleukin-6 (IL-6), to activate the transcription factor retinoid-related orphan nuclear receptor-γt (RORγt) and to produce IL-17 and IL-22.

Tr1 cells

(T regulatory type 1 cells) CD4+ T regulatory type 1 cells that produce large amounts of interleukin-10 (IL-10) through IL-10R signalling, and induce an anti-inflammatory response.

Ectopic expression

Enforced expression of a gene product, triggered by somatic mutation or genetic manipulation.

Intestinal crypts

Tube-like glands found in the lining of the colon and rectum.

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Zitvogel, L., Daillère, R., Roberti, M. et al. Anticancer effects of the microbiome and its products. Nat Rev Microbiol 15, 465–478 (2017). https://doi.org/10.1038/nrmicro.2017.44

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