**Author details**

*Current Cancer Treatment*

immune responses and promote carcinogenesis.

effects mediated through the GI tract.

**Conflict of interest**

tumour microenvironment is unique in that immunological tolerance is required to maintain a healthy intestinal environment, including maintenance of the "normal" microbiome, yet the presence of regulatory immune cells may impede antitumour

There is increasing evidence from preclinical mouse model systems and human studies that GI tract microbiota, such as *B. fragilis*, *Bifidobacterium*, *Faecalibacterium prausnitzii* and *Akkermansia muciniphila*, can directly influence response to treatment including immunotherapies and survival in some malignancies [187–193]. This effect is potentially mediated by bacteria stimulating activation of innate immune cells and downstream polarisation of Th-cell subsets towards Th1 cells [194]. The species and diversity of bacterium identified as influencing treatment response and survival vary, likely reflecting the complexity of the interactions involved, the diverse malignancies and populations within which those malignancies had arisen, and the number of bacterial species that have immunomodulatory

The influence of infections on initiation and promotion of cancer has been long recognised, but our understanding of the complex network of interactions between the host, the microbiome, the genetics of both the host and microbiome and the metabolome remains superficial. These interactions are not static, which, with the diversity of the GI tract environment, add to the challenge of deciphering what microbial species may be influencing the immune response in a tumour-promoting or tumour-suppressive manner. The complexity of microbial species and indeed the complexity of immune cells and their function mean that practically assaying and identifying individual species of bacteria, or subsets of immune cells, clinically in a prognostic or predictive sense is challenging. The more readily measureable microbial metabolome may provide a more clinically accessible read-out of this interaction. The wide-ranging impact that products of microbial metabolism have on immune cell function and polarity and therefore anticancer immunity has been underappreciated to this point. A greater understanding of how microbial metabolites influence the GI tumour microenvironment has the potential to expand

therapeutic options and improve survival of patients with GI cancers.

The authors declare no conflict of interest.

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Silke Neumann1 , Estelle M. Peyroux1 , Matt J. Woodall1 , Nick J. Shields1 , Sarah L. Young1 and Sharon T. Pattison<sup>2</sup> \*

1 Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand

2 Department of Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand

\*Address all correspondence to: sharon.pattison@otago.ac.nz

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
