Abstract
Metagenomic studies using next-generation sequencing technologies have revealed rich human intestinal microbiome, which likely influence host immunity and health conditions including cancer. Evidence indicates a biological link between altered microbiome and cancers in the digestive system. Escherichia coli and Bacteroides fragilis have been found to be enriched in colorectal mucosal tissues from patients with familial adenomatous polyposis that is caused by germline APC mutations. In addition, recent studies have found enrichment of certain oral bacteria, viruses, and fungi in tumor tissue and fecal specimens from patients with gastrointestinal cancer. An integrative approach is required to elucidate the role of microorganisms in the pathogenic process of gastrointestinal cancers, which develop through the accumulation of somatic genetic and epigenetic alterations in neoplastic cells, influenced by host genetic variations, immunity, microbiome, and environmental exposures. The transdisciplinary field of molecular pathological epidemiology (MPE) offers research frameworks to link germline genetics and environmental factors (including diet, lifestyle, and pharmacological factors) to pathologic phenotypes. The integration of microbiology into the MPE model (microbiology–MPE) can contribute to better understanding of the interactive role of environment, tumor cells, immune cells, and microbiome in various diseases. We review major clinical and experimental studies on the microbiome, and describe emerging evidence from the microbiology–MPE research in gastrointestinal cancers. Together with basic experimental research, this new research paradigm can help us to develop new prevention and treatment strategies for gastrointestinal cancers through targeting of the microbiome.
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Funding
This work was supported by US National Institutes of Health (NIH) Grants [R35 CA197735 to S.O.; R01 CA151993 to S.O.; R21 CA230873 to S.O.; R01 CA248857 to S.O.], and Cancer Research UK Grand Challenge Award (OPTIMISTICC, C10674/A27140 to S.O.). K.M. is supported by grants from JSPS KAKENHI (Grant Numbers 17H05094 and 20K17658). The content is solely the responsibility of the authors and does not necessarily represent the official views of NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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Mima, K., Kosumi, K., Baba, Y. et al. The microbiome, genetics, and gastrointestinal neoplasms: the evolving field of molecular pathological epidemiology to analyze the tumor–immune–microbiome interaction. Hum Genet 140, 725–746 (2021). https://doi.org/10.1007/s00439-020-02235-2
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DOI: https://doi.org/10.1007/s00439-020-02235-2