The microbiome, genetics, and gastrointestinal neoplasms: the evolving field of molecular pathological epidemiology to a
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The microbiome, genetics, and gastrointestinal neoplasms: the evolving field of molecular pathological epidemiology to analyze the tumor–immune–microbiome interaction Kosuke Mima1,2 · Keisuke Kosumi1,2 · Yoshifumi Baba2 · Tsuyoshi Hamada3 · Hideo Baba2 · Shuji Ogino4,5,6,7,8 Received: 4 May 2020 / Accepted: 23 October 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
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.
Introduction
Kosuke Mima, Keisuke Kosumi, and Yoshifumi Baba have contributed equally as co-first authors.
Carcinomas that arise in the digestive system, including upper and lower gastrointestinal tract, liver, gallbladder, extrahepatic bile duct, and pancreas, are collectively leading
* Kosuke Mima [email protected]
3
Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
* Shuji Ogino [email protected]
4
Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, 221 Longwood Ave., EBRC Room 404A, Boston, MA 02115, USA
5
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
6
Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA
7
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