Microbiome in cancer metastasis: biological insights and emerging spatial omics methods

Abstract

The role of the microbiome in cancer metastasis has emerged as a critical area of research, with growing evidence suggesting that microbial composition and interactions within the tumour microenvironment may significantly influence metastatic progression. This review explores the role of the microbiome in cancer metastasis, as well as potential key bacteria and their mechanisms through which they could impact tumour dissemination, seeding and growth. Biological models used to study metastasis are discussed to provide context for the further investigation of these interactions. In order to answer unresolved questions regarding the microbiome's involvement in metastatic dissemination, recent advancements in spatial biology techniques are examined, including spatial genomics, transcriptomics, proteomics and metabolomics, which enable the spatial mapping of microbial interactions within the tumour microenvironment. Additionally, multimodal-omics imaging approaches are highlighted for their potential to integrate multiple molecular layers, offering comprehensive insights into the microbiome's role in cancer metastasis. The review also addresses the challenges and limitations of these techniques, underscoring the complexity of studying microbiome-tumour interactions and offering directions for future research to better explore and target the microbiological landscape in metastatic cancer.

Keywords: cancer metastasis; host-microbiome interactions; microbiome; spatial omics; tumour microenvironment.

Figure 1

An overview of bacteria suggested to be involved in various stages of metastatic dissemination and cancer types. The varying microbiome-cancer interaction types are represented in the top left and indicated by different colours. The simplified stages of metastatic dissemination are indicated in the bottom left of the figure and denoted by the numbers 1 to 4. A systematic review of the current literature in terms of the different bacterial species suggested to be involved per cancer type is represented on the right of the figure. As an example, it is suggested that Fusobacterium nucleatum, a well-known cancer-associated bacterium, interacts with colorectal cancer in several ways and at several different stages. One of which is that it is known to affect the metastatic dissemination potential (1) via the direct interaction between bacterium and CRC cell (green). Created in BioRender (https://BioRender.com/q18n156).

Figure 2

An overview of some biological models that can be used to study aspects of metastasis. Models can be largely classified into the overarching types of in vitro, ex vivo, in vivo and in silico. In vitro assays include 2D and 3D cultures that can be used in a variety of assays as well as adapted to organ on chip or dual chamber assays. Ex vivo setups such as organotypic slide cultures and the analysis of patient samples are valuable approaches that allow for patient relevance. The gold standard remains the variety of in vivo murine models that are available for capturing the whole cascade or specific aspects with certain assays. And lastly, the recent vast advances in in silico analyses have also allowed it to also become a pilar of scientific exploration. Created in BioRender (https://BioRender.com/q18n156).

Figure 3

Comprehensive overview of spatial biology applied to the metastasis microbiome to examine spatial interaction between the microbiome and the cancer progression. Created in BioRender (https://BioRender.com/a19q596).