Cancer as microenvironmental, systemic and environmental diseases: opportunity for transdisciplinary microbiomics science

Abstract

Cancer is generally regarded as a localised disease, with the well-established role of the tumour microenvironment. However, the realm of cancer goes beyond the tumour microenvironment, and cancer should also be regarded as a systemic and environmental disease. The exposome (ie, the totality of exposures), which encompasses diets, supplements, smoking, alcohol, other lifestyle factors, medications, etc, likely alters the microbiome (inclusive of bacteria, viruses, archaea, fungi, parasites, etc) and immune system in various body sites and influences tumour phenotypes. The systemic metabolic/inflammatory status, which is likely influenced by exposures and intestinal physiological changes, may affect tissue microenvironment of colorectum and any other organs. Germline genomic factors can modify disease phenotypes via gene-by-environment interactions. Although challenges exist, it is crucial to advance not only basic experimental research that can analyse the effects of exposures, microorganisms and microenvironmental components on tumour evolution but also interdisciplinary human population research that can dissect the complex pathogenic roles of the exposome, microbiome and immunome. Metagenomic, metatranscriptomic and metabolomic analyses should be integrated into well-designed population research combined with advanced methodologies of artificial intelligence and molecular pathological epidemiology. Ideally, a prospective cohort study design that enables biospecimen (such as stool) collection before disease detection should be considered to address reverse causation and recall biases. Robust experimental and observational research together can provide insights into dynamic interactions between environmental exposures, microbiota, tumour and immunity during carcinogenesis processes, thereby helping us develop precision prevention and therapeutic strategies to ultimately reduce the cancer burden.

A budding concept with certain microbiota, anti-proliferative family proteins, and engram theory for the innovative treatment of colon cancer

“…Cancer has been regarded as a localized disease with a role of the tumor microenvironment, suggesting that cancer should be regarded as an environmental disease [65]. In particular, systemic inflammatory status influenced by physiological changes might affect the tissue microenvironment.…”

Influence of Foods and Nutrition on the Gut Microbiome and Implications for Intestinal Health

“…Accumulating evidence supports the role of dysbiosis of the gut microbiome in the development and progression of colorectal cancer (CRC) [ 115 ], which is the second leading cause of cancer-related death worldwide. Particularly, an increased amount of Fusobacterium nucleatum was identified in tumor tissues and fecal specimens from CRC patients [ 115 ]. Evidence also suggests that microbiota is genetically regulated in CRC.…”

“…Cancer is currently recognized as a microenvironmental, systemic and environmental disease, presenting new opportunities for transdisciplinary microbiomic studies [ 115 ]. This is also true for IBD.…”

“…In most current IBD research, dietary factors and the gut microbiome are separately studied in relation to disease or foods/nutrients in relation to stool microbes. These piecemeals can be integrated to obtain better insights into the disease etiology, as has been done in MPE studies in cancer, which integrated analyses of the exposure, microbiome and tumor microenvironment [ 115 , 118 ]. This will be a promising direction for researching dietary factors, microbiome, and personalized biomarkers in IBD.…”

Cancer Genetics and Clinical Research

“…Though we are not made of just genes. More than half of the risk of developing a certain disease is due to environmental factors [ 14 ], hence the need to develop a new analysis paradigm that includes the study of the exposome: a detailed map of all the environmental components to which an individual is exposed to throughout his life, and how those exposures affect their health. Yet the exposome analysis should also take into account what happens inside our body: oxidative stress phenomena or inflammatory processes contribute every day to create an extremely dynamic internal environment.…”