Integration of microbiology, molecular pathology, and epidemiology: a new paradigm to explore the pathogenesis of microbiome-driven neoplasms.

Molecular pathological epidemiology (MPE) is an integrative transdisciplinary field that addresses heterogeneous effects of exogenous and endogenous factors (collectively termed 'exposures'), including microorganisms, on disease occurrence and consequences, utilising molecular pathological signatures of the disease. In parallel with the paradigm of precision medicine, findings from MPE research can provide aetiological insights into tailored strategies of disease prevention and treatment. Due to the availability of molecular pathological tests on tumours, the MPE approach has been utilised predominantly in research on cancers including breast, lung, prostate, and colorectal carcinomas. Mounting evidence indicates that the microbiome (inclusive of viruses, bacteria, fungi, and parasites) plays an important role in a variety of human diseases including neoplasms. An alteration of the microbiome may be not only a cause of neoplasia but also an informative biomarker that indicates or mediates the association of an epidemiological exposure with health conditions and outcomes. To adequately educate and train investigators in this emerging area, we herein propose the integration of microbiology into the MPE model (termed 'microbiology-MPE'), which could improve our understanding of the complex interactions of environment, tumour cells, the immune system, and microbes in the tumour microenvironment during the carcinogenic process. Using this approach, we can examine how lifestyle factors, dietary patterns, medications, environmental exposures, and germline genetics influence cancer development and progression through impacting the microbial communities in the human body. Further integration of other disciplines (e.g. pharmacology, immunology, nutrition) into microbiology-MPE would expand this developing research frontier. With the advent of high-throughput next-generation sequencing technologies, researchers now have increasing access to large-scale metagenomics as well as other omics data (e.g. genomics, epigenomics, proteomics, and metabolomics) in population-based research. The integrative field of microbiology-MPE will open new opportunities for personalised medicine and public health.